PHA 326 Pharmaceutics: Final Exam
Rotary-Die Process
1. Liquid gelatin formed into two continuous ribbons 2. Ribbons brought together between rotating dies 3. At same time, metered fill material is injected between ribbons
Crystallization results in... (3)
1. Loss of aesthetic appeal 2. Instability 3. Flux disruption
What are the 3 ways suppositories may be prepared?
1. Molding from a melt 2. Compression 3. Hand-Molding
How to sterilize water? (2)
1. Multiple Distillation 2. Reverse Osmosis
Labeling: All dietary supplements must have... (7)
1. Must state that it's a dietary supplement 2. Accurate disclosure of contents 3. Must have supplement facts table including Name, Quantity and %DV of each ingredient 4. Additional Ingredients (Excipients) 5. Disclosure of key allergens 6. Disclaimer: "These statements have not been evaluated by the FDA. This product is not intended to diagnose, cure, treat, or prevent any disease." 7. Must have phone # or address through which consumers can report any adverse events
Advantages of Aerosol Dosage Form: (4)
1. No contamination of residual product; sterility can be maintained 2. Particle size of mist controlled by formulation & valve design; dosage controlled by metering valves 3. Protects against moisture, oxygen, & light 4. Cool sensation for topical delivery
Name 6 forms of solutions
1. Oral 2. Otic 3. Nasal 4. Topical 5. Ophthalmic (sterile) 6. Parenteral (sterile)
What are the 4 parts of Film Coating?
1. Polymer 2. Plasticizer 3. Colorant 4. Solvent
Potential immune response against the therapeutic protein? (2)
1. Protein Neutralization 2. Allergic reaction
Name 2 examples of local suppository effects.
1. Rectal Suppository for Hemorrhoids 2. Vaginal Suppository for Fungal Infection
Name 2 Surface Sampling Methods
1. Rodac Plates 2. Swab-Rinse Test
"reasonably be expected to be safe" can be satisfied by... (2)
1. Safety evidence from study and/or 2. history of use
Name 2 examples of systemic suppository effects.
1. Sedatives 2. Analgesics
Name 3 air sampling methods.
1. Settling Plates (Viable) 2. Electronic Air Particle Counters (Viable & Nonviable) 3. Centrifugal Air Sampler (Viable & Nonviable)
What are the 4 types of Aerosols?
1. Space Sprays 2. Surface sprays 3. Foams 4. Inhalation Aerosols
Name 3 factors that are directly proportional to permeability.
1. Surface Area 2. Partition Coefficient 3. Diffusion Coefficient
Name 4 factors that directly affect drug absorption?
1. Surface Area 2. Partition Coefficient 3. Diffusion Coefficient 4. Membrane Thickness
What are the 5 parts of Quality Control Specification? (In-House)
1. Tablet Hardness 2. Tablet Friability 3. Tablet Thickness 4. Tablet Weight 5. Content Uniformity
4 steps to tablet compression:
1. Tablet machines may be single station or rotary presses 2. Granulation fills die cavity as lower punch drops 3. The Upper punch then lowers and compresses the material into a tablet 4. Upper punch finally retracts and lower punch rises to eject the tablet
Controlled Release Dosage Form Advantages: (4)
1. Targeting/Specificity 2. Membrane crossing 3. Drug protection 4. Decrease toxicity
Diffusion-Controlled Release (2)
1. The drug release is controlled by the diffusion of the drug molecules. 2. For pure diffusion-controlled delivery dosage, drug is dissolved and remains dissolved in the final product.
What are the 2 types of passive diffusion?
1. Transcellular Diffusion 2. Paracellular Diffusion
What are the 3 steps to aerosol usage?
1. Vapor pressure of propellant exerts pressure in all directions in a aerosol container 2. Upon actuation of valve, this pressure forces the liquid up the dip tube and out the valve orifice 3. Upon release, propellant vaporizes to break the formulation into a fine mist
What are the 2 ways granules can be made?
1. Wet Granulation Method 2. Dry Granulation Method
What are the 3 methods to making tablets?
1. Wet Granulation Method 2. Dry Granulation Method 3. Direct Compression
What are the 3 ways to create RDT's
1. Zydis delivery system - lyophilize a foam of drug/gelatin/sugar in a mold that also serves as the unit dose dispensing package, e.g., Claritin (loratadine) 2. soft direct compression (e.g., Wow-Tab, Yamanouchi-Shaklee Pharma) 3. Fast dissolving excipients + effervescent material, e.g., OraSolv & DuraSolv (CIMA Labs)
Suppository Compression is used for... (3)
1. heat sensitive drugs 2. high percentage of solids 3. formulation forced into mold openings
Ocular Bioavailability considers... (3) to increase...
1. lacrimal drainage 2. protein binding 3. lysozyme; unionized proportion
Particles dispersed in liquid media may become charged in two ways:
1. selective adsorption of ionic species present in solution 2. ionization of groups (such as COOH) that may be situated at the surface of the particle
Health Claims
A link between a food substance/dietary supplement and disease or a health-related condition. Must be authorized by FDA before they may be used on label (related to disease)
Eutectic Mixture
A mixture of two or more solid components that becomes a liquid on mixing (without change in temperature)
How to apply an eye ointment?
A ribbon of medication is placed directly into the lower lid at bedtime
On a molar basis, what takes the longest amount of time to be emptied from the stomach? Fats, Proteins, or Carbs?
Fats
cocoa butter cocoa butter substitutes e.g., wecobee®, witepsol®, fattibase®
Fatty or Oleaginous Suppository Bases
Regarding GI motility and the fed mode, what rate order reaction process would liquid that is leaving be?
First Order
At what rate order would liquid leave the stomach? Maria #3
First order
What is the kinetic energy order at which liquids leave the stomach? Domonique #2
First order
What rate order process does absorption occur? Savannah #1
First order
Emulsion; e.g. shaving cream, hemorrhoid cream
Foam aerosol
Tertiary Structure
Folded Protein
Which of these factors increase absorption when taking a dose of medication? a. A man with GERD b. A woman who is 26 weeks pregnant c. A young patient who is also taking erythromycin d. A patient with Type I Diabetes e. After a man has consumed all you can eat pancakes at IHOP
c. A young patient who is also taking erythromycin
Percolation
The downward movement of water through soil and rock due to gravity.
Dissolution/Diffusion-Controlled Release: Matrix Dissolution Control:
The drug is distributed in an insoluble polymer matrix.
Dissolution-Controlled Release
The drug release is controlled by the dissolution rate of a drug in the GI medium.
Which of the following would *increase* when a drug is more rapidly absorbed? a. AUC b. Efficacy c. Cmax d. Potency e. Tmax
c. Cmax
Which of the following is NOT a part of the stomach? a. Fundus b. Body c. Duodenum d. Antrum
c. Duodenum
For products made with high risk procedures, a program of...
end-product sterility testing is also required, according to a formal sampling plan.
Effect of Blood Flow on Absorption: Perfusion is rate limiting step therefore...
every other step would be faster.
During ________________, drugs are ______________ (by kidney), which removes them and/or their metabolites from the body
excretion; excreted
Gas Sterilization
exposure to ethylene oxide gas, diluted with an inert (chemically-inactive) gas, for heat and moisture sensitive materials
Salt form dissolves ____________ than original drug form
faster
Advantages of RDT's (3)
faster absorption increased compliance pediatrics and elderly
What does a suppository density factor tell us?
The relative density compared to cocoa butter
Structure/Function Claim
The role of a nutrient or dietary ingredient intended to affect normal structure or function in humans and *must include "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease" on label.*
What does the valve control?
The type of spray
Sonophoresis
The use of ultrasound to drive molecules into and across skin
A
Therapeutically Equivalent
AP
Therapeutically Equivalent Aqueous Injections
AO
Therapeutically Equivalent Injectable Oils
AN
Therapeutically Equivalent Solution/Powder for Aerosolization
AT
Therapeutically Equivalent Topicals
AA
Therapeutically Equivalent and Not Presenting Problem(s)
Drug concentrations more often measured in plasma rather than whole blood or serum. Why?
Whole blood has multiple components, while plasma is more refined to...
Shear thinning system means...
With force, viscosity is reduced
Prefabricated Dosage: Dose is calculated based on...
fewest dosage units
Drug product is a...
finished dosage form
Liquids leaving the stomach follow ________-order kinetics.
first
Absorption is a ___________ ____________ _____________ process
first order kinetic
GI Motility (Fed): Liquids generally exit the stomach via a...
first order process
Hydrocarbons are __________________
flammable
LVPs typically used as means of... (3)
fluid replacement, electrolyte-balance restoration, or for total parenteral nutrition (TPN)
Sterile means...
free of live microorganisms
Net movement via passive diffusion occurs...
from a region of higher concentration to a region of lower concentration.
Carbopols, hydroxyethylcellulose, PLO (pluronic lecithin organogel)
gels
Multi-Source meaning
generic
Water soluble and water-miscible Suppository Bases
glycerinated gelatin polyethylene glycol bases (e.g., polybase)
Why is gauge a measure of the outside diameter?
going into the vein
Lozenges (Troches)
hard candy or soft sugar base (dissolve slowly or chew for localized effects
Swab-Rinse test are used for...
hard to reach areas
The pH of the environment in which the salt is exposed...
has less effect on dissolution rate
According to USP 797, getting drug from tablet is a ________ risk procedure.
high
Silicone hydrogels have allowed extended wear due to...
high oxygen permeability
Aspirin, an acidic drug, will dissolve faster in a...
high pH solution
Compounding sterile preparations from non-sterile ingredients is always categorized as...
high risk compounding.
The unstable polymorphic form has a ___________ solubility than the stable form.
higher
Acids dissolve better/faster at a ______________ pH because...
higher; they are more ionized in a basic environment, which makes them more water-soluble.
"Acids are going to dissolve faster at a ____________ pH because..."
higher; they will be more ionized consequently making them more water-soluble
Volatile
highly unstable; explosive
Endocrine/G-Cells
hormone gastrin that stimulates release of HCl and pepsinogen
Differential stripping checks...
how much drug is in a hair follicle
Covalent bonds can be broken through ________________ reactions
hydrolysis
Chemical Incompatibility
hydrolysis, oxidation (may result in color change), photolysis, complexation, compatibility of preservative etc. *Amber over-wrap to keep from photolysis
The holes created by skin microporation are _____________________.
hydrophilic
The dissolution rate of a weak acid would generally dissolve better...
in a basic solution due to it being ionized at a higher pH
Glass Ampule: "A filter needle must be used...
in one of the steps"
Metabolite
inactive form of the original drug
How to increase ophthalmic sustainability?
increase the viscosity, make it thicker (SPMC) or use an insert or ointment
Decrease in P-gp activity may cause a(n) _________________ in absorption for P-gp substate drugs, and why?
increase; for obvious reasons
Drug freely passes through membrane so the ___________________ is the rate limiting step.
blood flow (Perfusion)
Cornea, lens, & vitreous body are all transparent media with no...
blood vessels
Sterilization by Filtration Check filter integrity by...
bubble-point test
Vaginal suppositories are generally for more _______________ effects while Rectal suppositories may be used for _______________ and _______________ effects.
localized; localized; systemic
Every component of administration is sterile, therefore according to USP 797, this procedure is _______ risk.
low
Weak acid would show more absorption at a
low pH
Most of the products prepared in pharmacy I.V. admixture programs are...
low risk products
Facility Design: IV Room
low traffic area; LAFW in low traffic area within the IV room
Bases dissolve better/faster at a ______________ pH because...
lower; they are more ionized in an acidic environment, which makes them more water-soluble.
Excess ________________ may result in poor disintegration and/or delayed dissolution.
lubricant
Equivalent weight in milligram is...
mEq
During extemporaneous preparation (fill by hand), the producer will generally...
make 5-10% extra powder
Biological Product (Biologics)
means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, ..., applicable to the prevention, treatment, or cure of a disease or condition of human beings." [from 42 U.S. Code § 262(i)(1)] This includes blood-derived products, vaccines, in vivo diagnostic allergenic products, immunoglobulin products, products containing cells or microorganisms, and most protein products.
Sterilization
means the "complete" destruction of all living organisms and their spores or their complete removal from the preparation
Delayed Release Dosage Forms
means the release of the drug occurs in certain period of time after administration. The most common example of delayed release dosage form is *enteric-coated tablets*, which remain intact in the stomach and release their medication within the intestinal tract.
Gauge
measure of the outside measurement of the needle shaft
Filter needles are used when:
medications are being withdrawn from a glass ampule for admixture compounding to filter bacteria, etc.
According to USP 797, TPN is a __________ risk procedure.
medium
TPN is essentially a ______________ risk
medium
Prior to combination, the oleaginous components are _______________ and then the aqueous components are _______________
melted; heated
h =
membrane thickness
During ________________, drugs are biotransformed perhaps to several different compounds by enzymes evolved to cope with natural materials - this may increase, decrease or change drug actions
metabolism
At a concentration that is characteristic of each amphiphile, these molecules will aggregate to produce _________________.
micelles
Concentrated sugar solutions are resistant to...
microbial growth
Water and Propylene Glycol are...
miscible (dissolves homogeneously)
An elevated pH would cause a weak base to dissolve (more/less)...
more slowly
Drug Absorption
movement of drug from site of administration into the blood
A metered dose inhaler is designed to deliver an asthma medication - Will it be single or multiple dose?
multiple
Interchangeable or Interchangeability
must provide sufficient information to demonstrate biosimilarity *and* also to demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient and, if the biological product is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.
A protein needs be in it's _____________ state to achieve a biological response
native
Chemical and physical instability decreases the concentration of the __________________________________ in the product as a function of time.
native, active protein
Lyophobic systems
need special dispersion or condensation methods, e.g., gold, silver, sulfur "Hates the solvent"
Biological safety cabinet (BSC) is a _______________ pressure hood that protects personnel, product and environment
negative
Benzyl alcohol is toxic to
neonates
Polymorphs: In solution, there is generally... However, if the crystalline solubilities of the various compounds are different, what may vary?
no difference; absorption
Ready-to-use systems such as ADD-Vantage (Hospira) or Monovial safety guard (BD) can...
prevent much of the waste from the self-imposed expiration dating.
Is USP private or government?
private
Natural colloids aka
proteins
The targets for most conventional drugs are ______________.
proteins
Steam Sterilization does NOT remove...
pyrogens
Dissolves in the mouth in about 15-30 secs
rapid-dissolving tablets
The slowest step in a multistep process?
rate limiting step
Time to plateau is related to the...
rate of absorption
dC/dt =
rate of diffusion (PDA/h)•(C(AD) - C(P))
Large, Polar, Water-soluble molecules such as Gentamicin may be
readily absorbed in muscle tissue
Comminution: Trituration
reduce particle size by grinding
Comminution: Levigation
reduce particle size by using a liquid/wetting agent
Comminution: Spatulation
reduce particle size by using an ointment slab and spatula
Transcellular Transport w/ Intracellular Metabolism would typically...
reduce the bioavailability of the drug
Bioequivalence
relative therapeutic effectiveness of chemically equivalent drugs.
Controlled Release Systems: The drug must be effective in a...
relatively small dose.
If the pH remains the same the degree of ionization should...
remain the same
Carrier Mediated Transport only...
responds to specific functional groups
Prior to infusion, admixtures should be...
returned to room temperature and inspected for clarity, freedom from particulates, etc.
Soft gelatin capsules are generally produced via the...
rotary die process
Orange Peel Effect
roughness of tablet surface due to failure of spray droplets to coalesce
Maintaining _________________ is the best approach but may not be feasible.
saturation
Parietal Cells
secrete HCl and intrinsic factor
Chief Cells
secrete pepsinogen
Lamination
separation of a tablet into two or more distinct layers
Ophthalmic suspensions must be...
shaken before use and be less than 10 µm
Pseudoplastic flow curve aka...
shear thinning system
Starting material to make a parenteral formulation is...
water for injection, which already doesn't have pyrogens due to them being removed via reverse osmosis or multiple distillations
Hydrophilic ointment, USP is an example of a...
water-removable base
Magnesium sterate is a __________________________ excipient that may not ______________.
water-soluble, dissolve
Polysorbate 80
wetting agent
When is dry granulation used?
when drug is moisture- or heat-sensitive and/or powder has cohesive properties
What do you get if you decolorize yellow petroleum?
white petroleum...duh
Lanolin is...
wool fat/grease
Lanolin is obtained from...
wool of sheep
Ointments Compendial Requirements: Products intended for rectal, urethral, or vaginal use should be tested for...
yeast and molds
Can anhydrous substances absorb water?
yes
GI Motility (Fed): "Small enough sized" solids generally exit the stomach via a...
zero order process
Around what pH level would an empty stomach be?
~1-2
What is generally the pH range of the large intestine?
~5.5-7
What is generally the pH of the small intestine?
~6
Example of a Nonionic surfactant
Polysorbate 80
Crystallization Inhibitor?
Polyvinylpyrrolidone (PVP)
Where does yellow wax come from?
"Honey comb of the bee"
Deflocculated Appearance
"Pleasing" lol
First-Generation Biopharmaceutical
"Straight forward copy of a human hormone or some other protein" Exact copy of hormone Produced by biotechnology via transfecting the human gene into some suitable expression. The first biopharmaceutical product: Human Insulin produced by e.Coli via dna recombination
[AUC]interval =
((C1 + C2)/2)(t2 - t1)
[AUC]interval =
((C₁ + C₂)/2)(t₂ - t₁)
For low, medium, or high-risk level CSPs used within 48 hours
(ISO Class 8(ISO Class 7 or 8(ISO Class 5 PEC)))
For low-risk CSP with 12 hr or less BUD
(Segregated Compounding Area (ISO Class 5 PEC))
Used on MDVs to permit introduction of a needle from a hypodermic syringe
Rubber closures
USP permits preservatives, buffers, solubilizers, antioxidants or other additives in _________ if needed
SVP's
__________ are generally < 100 mL
SVP's
USP: direct inoculation & membrane filtration method
Sterility Test
Physical removal of microorganisms by a 0.2 micron membrane filter
Sterilization by Filtration
Rate Limiting Step of Epidermis for percutaneous absorption?
Stratum Corneum
________________ ________________ or horny layer is the outer layer
Stratum Corneum
What type of claim and is it allowed? "Promotes healthy cholesterol level"
Structure/Function Claim that is allowed
Rheology
Study of the flow of materials
Sodium Bicarbonate and Citric Acid are generally used together in _____________________ tablets
effervescent
Polymers
very large molecules consisting of repeating structural units, or monomers, connected by covalent bonds.
HLB 3-6
w/o
All dosage forms must be taken with __________.
water
How to keep from overheating?
water bath
____________ ___________________ is the inner region of viable cells
Stratum germinativum (or stratum basale or basal layer)
Thixotropy
Stress can cause a breakdown of structure that does not reform immediately when the stress is removed
What type of claim and is it allowed? "Calcium builds strong bones"
Structure/Function Claim that is allowed
Covert
(adj.) hidden, disguised, purposefully kept secret; sheltered, secluded
Overt
(adj.) open, not hidden, expressed or revealed in a way that is easily recognized
What type of absorption base is Hydrophilic petrolatum, USP?
Anhydrous
Viscosity and removal of ear moisture
Anhydrous glycerin
COO-
Anionic Surfactant
Piggyback IV administration Advantages: (4)
1. Additional venipuncture not needed 2. Medication can be given at intervals 3. Incompatibilities avoided 4. Some dilution (within piggy-bag) possible
What are the possible consequences of protein unfolding?
1. Adsorption 2. Aggregation
Stepwise Approach to Demonstrating Biosimilarity: (4)
1. Analytical Studies 2. Animal Studies 3. Human Studies 4. Clinical Studies
What are the 2 types of aerosol inhalers?
1. Liquid 2. Dry Powder
What are the 3 types of Petroleum?
1. Liquid Hydrocarbons 2. Semisolid Hydrocarbons 3. Solid Hydrocarbons
Inward airflow, vertical downward HEPA filtered air, and HEPA filtered exhausted air
Biological safety cabinet (BSC)
Operated continuously
Biological safety cabinet (BSC)
e.g., behavior of blood, mucus, & synovial fluid
Biorheology
Product first then valve
Cold filling
Approved, certified, water soluble FD&C dyes, mixtures, or their corresponding lakes may be used
Colorants
distinguish one dose from another, and provide aesthetics
Colorants
Dietary Supplement and Nonprescription Drug Consumer Act (December 22, 2006)
Company must inform FDA of adverse event within 15 days of event
Stepwise Approach to Demonstrating Biosimilarity: 1. Analytical Studies: (2)
Comparative Structural and Functional Analysis
Establishes official reference material
Compendia (USP)
Establishes official testing methods
Compendia (USP)
Promoting the Quality of Medicines (PQM) - strengthen quality assurance and quality control systems to better ensure the quality of medicines that reach patients primarily in developing countries
Compendia (USP)
Sets official standards
Compendia (USP)
Dual-compartment bags
Completely separated until manually combined
Critical Micelle Concentration (CMC)
Concentration at which detergents form spherical aggregates
Solubility
Concentration of solute in a saturated solution at a certain temperature
Sorption of drug =
Container may leach some of the product
CR
Controlled Release
Concave Punches =
Convex Tablets
Semisolid viscous emulsions of o/w or w/o type
Creams
PVC containers may have __________ as plasticizer
DEHP
_______________ particle size to increase bioavailability/absorption of suppository.
Decrease
What is the effect on bioavailability of metabolism of a drug (as opposed to elimination)?
Decreased Bioavailability
Tmax: Increased Rate
Decreases
Antacids (Al, Mg)
Delays Gastric Emptying
Anticholinergics
Delays Gastric Emptying
Diabetic Gastroparesis
Delays Gastric Emptying
GERD
Delays Gastric Emptying
Gastric Carcinoma
Delays Gastric Emptying
Gastric Ulcer
Delays Gastric Emptying
Gastritis
Delays Gastric Emptying
Hypothyroidism
Delays Gastric Emptying
Isoniazid
Delays Gastric Emptying
Migraine (Pain in general)
Delays Gastric Emptying
Narcotic analgesics (opioids)
Delays Gastric Emptying
Pregnancy
Delays Gastric Emptying
Pyloric Stenosis
Delays Gastric Emptying
Tricyclic antidepressants
Delays Gastric Emptying
Altered how dietary supplements are regulated and labeled
Dietary Supplement Health and Education Act of 1994
Amendment to FDC Act
Dietary Supplement Health and Education Act of 1994
D =
Diffusion Coefficient, measure of how well compound can diffuse
Lactose
Diluent
What alters the size of the tablet so that it can be handled properly?
Diluent
Provide bulk to make the tablet a practical size for compression
Diluents
e.g., lactose, microcrystalline cellulose, dicalcium phosphate, powdered sucrose
Diluents
e.g., lactose, microcrystalline cellulose, pre-gelatinized starch
Diluents
These facilitate the breakup of tablet after administration, e.g., (corn)starch
Disintegrants
Drug crystals exposed to GI fluids → Drug dissolved in GI fluids
Dissolution
What would be the expected rate limiting step in the oral absorption process for a solid poorly soluble and highly permeable drug?
Dissolution
Dissolution
Dissolving due to a solute passing into a solvent
Drug in Blood ⇌ Drug in Tissue
Distribution
__________________ affects concentration at site of action and sites of excretion and biotransformation
Distribution
Frequency of Dosing
Dosage & Regimen
Large/Small Dosage
Dosage & Regimen
Extended Release Dosage Forms
Dosage form maintains therapeutic blood levels or tissue levels of the drug for a prolonged time.
Suppository Disadvantage(s)
Drug absorption may be erratic (Not Reproducible)
If Cad > Cp
Drug is diluted and delivered to the tissues
Pharmaceutical Equivalents
Drug products containing the same active ingredient(s), same dosage form and route of administration and identical in strength or concentration.
Pharmaceutical Alternatives
Drug products that contain the identical therapeutic moiety or its precursor but not necessarily in the same amount or dosage form or as the same salt or ester
Dehydration followed by oxidation
Dry Heat Sterilization
Glassware can be covered with aluminum foil and sterilized & depyrogenated
Dry Heat Sterilization
What sterilizes the vial used in filter sterilization?
Dry Heat Sterilization
Risk of microbial growth, which can cause lung infections, is greater in liquids than in solids
Dry Powder Inhaler
Unlike liquid formulations, aerosol particles contain drug in very concentrated form, allowing delivery of therapeutic dose in one to three puffs
Dry Powder Inhaler
For Injection
Dry soluble products with or without excipients and ready to be combined with a solvent
For Injectable Suspension:
Dry, insoluble and unstable products, ready to be suspended in a vehicle
Non-Viable Contamination
Dust (Carriers of microbes)
Rheological Analysis
Elasticity and viscosity
Drug in Blood → Excretion/Metabolism
Elimination
Can dissolve both water-soluble and alcohol soluble components
Elixers
Clear, sweetened, hydroalcoholic liquids intended for oral use.
Elixirs
Sodium Lauryl Sulfate
Emulsifier/Surfactant
Carbohydrate materials such as acacia, tragacanth etc
Emulsifying agents
Wetting agents - anionic, cationic, or nonionic
Emulsifying agents
Thermodynamically unstable
Emulsion
two immiscible liquid phases, one of which is dispersed as globules in the other
Emulsion Dispersed System
Endocrine vs Exocrine Gland
Endocrine glands secrete hormones directly into the bloodstream while exocrine glands secrete their products into ducts
__________________ are potent and very stable; they will pass through 0.2 µm filters and are not destroyed by autoclaving
Endotoxins
Second-Generation Biopharmaceutical
Engineered Deliberate alteration to the product prior to the transfection process to produce a structure that is different or changed. Ex. Change the sequencing of amino acids, inhibit the carbohydrate residues on the proteins, covalent attachment of PEG or some other material
Small Intestine Secretions:
Enzymes Bile (Surfactant) Bicarbonate
________________ is commonly used as a cosolvent in HFA aerosol inhalers
Ethanol
How to increase absorption of rectal suppository in colon?
Evacuant Enema prior to administration
Excretion vs Metabolism
Excretion does *not* change the original drug molecule, while Metabolism chemically alters the original molecule
ER
Extended Release
η =
F/G, where η is the viscosity
Post October 1994, *New Dietary Ingredients* must inform _______ of intent to market and provide...
FDA; information stating that the product will "reasonably be expected to be safe"
...transport of drug requires a specific drug structure
Facilitated and Active
...transport of drug requires special membrane proteins
Facilitated and Active
...transport only occurs in one direction
Facilitated and Active
...transport process can be inhibited
Facilitated and Active
...transport process can be saturated
Facilitated and Active
(T/F?) Dietary Supplements are unregulated.
False
(T/F?) Dietary Supplements like drugs require FDA review and approval prior to being sold in the market place.
False
(T/F?) Efficacy data are needed before dietary supplements are sold.
False
(T/F?) For a drug undergoing passive diffusion, movement of drug across the membrane stops when drug concentration on both sides of the membrane becomes equal.
False
(T/F?) Passive diffusion is usually a zero-order rate process. Zobia #3
False
(T/F?) Polar drugs would primarily be absorbed from the small intestine by the transcellular route.
False
(T/F?) There are no current regulations to ensure product quality of dietary supplements
False
T/F? The large intestine has villi.
False
Primary engineering control (PEC) must be at least...
ISO 5
HEPA Filters: LAWF is placed in a buffer area that should meet _________________ (Class 10,000) specifications. While the anteroom or support area, which is outside the buffer area, should be __________________ (Class 100,000)
ISO Class 7; ISO Class 8
Transdermal patches simulate
IV Infusion
Free from particulates
IV fluids, parenterals in general ...obviously
TPN solutions are administered via...
IV pumps
What are the biological barriers a drug must pass when going from: (4) IV/SubQ/IM → Target
IV/SubQ/IM → Blood Vessels → Tissue → Target
Sterile water for injection is not used for _______ because...
IV; it is not isosmotic with blood
Parenterals Advantages (3)
Immediate Response Better Control Medical Supervision
Stepwise Approach to Demonstrating Biosimilarity: 4. Clinical Studies: (3)
Immunogenicity, safety, and effectiveness
Dissolution-Controlled Release vs. Diffusion-Controlled Release
In *dissolution controlled release* system, the dissolution of drug is the step that limits the release rate. After the drug dissolves, it releases either from matrix or membrane system through diffusion. But here, dissolution is the limiting step for release rate. In *diffusion-controlled release* system, drug actually is in solution state either in matrix or membrane system. So the diffusion of drug out of delivery device is the rate limiting step. For pure diffusion-controlled delivery dosage, drug is dissolved and remains dissolved in the final formulated produce. Both of the dosages are formed either by incorporating the drug in an insoluble polymer as in matrix system, or coating drug particles with polymeric materials, as in membrane system.
Where are acids going to be more unionized?
In an acidic environment
Terminal Sterilization
In the end, your assay level is the best, 10⁻⁶, which means there is a 1 in 1 millionth chance there is bacteria/contamination within the preparation.
Excipients
Inactive drug ingredient(s)
Physical Incompatibility
Incompatibility between drug and and container or diluent, or with another drug; change in color or appearance; change in acid-base environment; pH of things being mixed; solubility problems *Solubility: Diazepam + Ethanol/PEG instantaneously evaporating within IV bag so go slow.
How to increase concentration of a drug via percutaneous absorption?
Increase surface area
How can you include more in a capsule?
Increase the bulk density
Distinguishing characteristic of the small intestine?
Increased surface area due to microvilli
AUC: Increased Extent
Increases
Cmax: Increased Extent
Increases
Cmax: Increased Rate
Increases
Cholecystitis
Increases Gastric Emptying
Domperidone
Increases Gastric Emptying
Duodenal ulcer
Increases Gastric Emptying
Erythromycin
Increases Gastric Emptying
Hyperthyroidism
Increases Gastric Emptying
Methoclopramide
Increases Gastric Emptying
What type of claim and is it allowed? "Helps prevent mild memory loss associated with aging"
Structure/Function Claim that is allowed
LA
Long Action
Flocculated State of Particles
Loose aggregates
Pylorus
Lower section of the stomach that facilitates emptying of the contents into the small intestine.
Magnesium Stereate
Lubricant
e.g., magnesium stearate
Lubricant
Prevents adhesion of powder to surfaces of dies and punches and may improve flow
Lubricants
e.g., magnesium stearate, and talc
Lubricants
____________________________, if possible for a particular protein, can greatly reduce all these stability problems because the product is kept dry until just before use.
Lyophilization
Regarding absorption from muscle or subcutaneous tissue, which molecular weight crosses capillaries readily?
MW < 5000
Equivalent Weight =
MW/valence *Valence = sum of positive or negative ions
Fundus
Main upper portion of the stomach. The word fundus means that part farthest from the opening of an organ (in this case the part of the stomach emptying into the small intestine). In the stomach, it refers to the rounded enlarged area at the top of the stomach.
_____________ micro-needles dissolve in the skin
Maltose
Crystallization is used for ______________ injection
Mannitol
Diagnostic Aid for Renal Function Test
Mannitol Injection
Primary objective: to create a system of programs, policies, processes, and facilities that prevent errors and defects
Manufacturer
Irritation Testing: Cell Culture:
MatTek Epiderm™ model = skin irritation test
Problems with Plastics? (3)
May leach constituents into product or allow sorption of drug or allow permeation of vapors Less clarity Sterilization methods limited
Microdermabrasion
Mechanical exfoliation that involves shooting aluminum oxide or other crystals at the skin with a hand-held device that exfoliates dead cells.
Viscoelasticity
Mechanical properties of materials that exhibit both viscous properties of liquids and elastic properties of solids
_________________ ointments are used as vehicles, while ___________________ ointments are used as emollients or lubricants (Occlusive)
Medicated; Non-medicated
TPN is an example of
Medium-Risk Compounding
___________________________ control the amount of material discharged upon actuation; limited volume discharged so may not work for high dose drugs
Metering valves Example: Pro-Air, Ventolin
______________________ remain open for up to 72 hrs under occluded conditions
Microchannels
< 0.2 microns - dispersed phase
Microemulsions
homogeneous, transparent & stable
Microemulsions
surfactant & cosurfactant
Microemulsions
electrolytes, trace elements & vitamins added as needed
Micronutrients
Drug is dispersed in the polymer matrix
Microsphere Formulation (SubQ & IM) *Biodegradable
What is gastric emptying controlled by? (Fasting)
Migrating Motor Complex (MMC)
Petroleum: Liquid Hydrocarbons
Mineral Oil
MEC
Minimum Effective Concentration
MTC
Minimum Toxic Concentration
__________ heat causes the denaturation of proteins
Moist
Solvate
Molecules of solvent incorporated into solid crystalline state
How much to convert stomach to fed mode?
More than 150 mL
Mucoid Cells
Mucus-secreting cells (surface epithelial cells)
Max Potassium amount given
NMT 30 mEq/hour
Solubility
Physical/Chemical Properties of Drug (API)
The energy required for a drug to escape from a crystalline structure compared to an amorphous solid is due to the amorphous solid being...
(adj.) shapeless, without definite form; of no particular type or character; without organization, unity, or cohesion
When Potassium Penicillin G was given IV to volunteers, 80% of a 500 mg dose was recovered unchanged in the urine. 280 mg unchanged drug was recovered in the urine when the same dose was given IM to the same subjects. (A) Calculate the availability of the IM injection and (B) describe which type of availability it is with reasoning.
*(A):* IV: (500)(0.8) = 400 mg IM: (500)(0.56) = 280 mg Test = IM Availability F = Test/Standard F = 280/400 = 0.7 Therefore, 70% of the IM dose was absorbed. *(B):* Absolute Availability because the calculated value is being compared to the standard dose
Adulteration vs Contamination
*Adulteration*: Addition of impure or inferior components not usually a component of the substance; removal of critical ingredients. Usually done intentionally *Contamination*: Presence of foreign material that makes substance impure. Usually done unintentionally.
What should be heated and what should be melted prior to compounding for this vanishing cream? Lanolin 2 g Cetyl alcohol 1 g Mineral oil 5 g Stearic acid 9 g Pot. Hydroxide 0.5 g Propylene glycol 5 g Purified water 77.5 g
*Melted:* Lanolin 2 g Cetyl alcohol 1 g Mineral oil 5 g Stearic acid 9 g *Heated:* Pot. Hydroxide 0.5 g Propylene glycol 5 g Purified water 77.5 g
Drug in Tissue ⇌ Pharmacologic Effect
*Not that indicative of effectiveness, therefore "Drug in Blood" is examined
Meta stable polymorphic form
*SLOW* rate conversion (years)
Density Factor is 2 and we need to add 1 g of drug to suppository. The blank cocoa butter suppository weighs 2 g. a. What is the weight of the medicated? b. What is the weight of the base? c. How much base was displaced?
*a.* 2 = (1)/(2-x+1) *Cross Multiply 4-2x+2 = 1 5 = 2x 5/2 = 2x/2 5/2 = x *2.5 g = x* ______________________________ *b.* 2.5 - 1 = *1.5 g* _______________________________ *c.* 1.5 - 1 = *0.5 g*
Surface Area
Physical/Chemical Properties of Drug (API)
Breathing pattern, vasculature, lung anatomy, Mucociliary clearance, disease, coordination of aerosol generation & inspiration
Physiological Factors Affecting Particle Deposition
Factors Affecting Gastric Emptying via the Duodenum Feedback Mechanism: Meal Type/Caloric Value:
-Emptying generally the same for fats, proteins, and carbs of same caloric value -The greater # of calories, the slower the emptying
pH-Partition Theory: Assumptions:
-Gastrointestinal Tract (GIT) is a simple lipid barrier -pH and pKa of API are important -Only non-ionized form is absorbed/cross
What are extravascular routes of administration?
-Oral -Transdermal -Rectal -Nasal -Ophthalmic -Otic -Pulmonary -Buccal -Sub everything *Literally everything except intravenously*
Why would a drug be manufactured as a prodrug?
-Poor absorption -Poor solubility -Instability -Poor distribution -"Bad" taste -Pain on injection
Nanoparticles
Polymeric particles between 10 nanometers (nm) and 1000 nm in size
GI Motility: Name 5 Characteristics of Fed Mode: (5)
-one motility pattern -regular frequent contractions -continues while food is present -only liquids and small particles empty -< 2-8 mm will empty
GI Motility (Fasting): Phase IV
0-5 minutes Decline in activity
Intradermal Amount
0.1 mL
Filter size to sterilize
0.2 µm
Dispersed System: Coarse Dispersions:
0.5 μm or greater
Isotonicity Value
0.6-2.0 % NaCl or its osmotic equivalent
Dispersed System: Colloidal Dispersions size:
1 nm - 0.5 μm
Log P of ____-_____ is desired
1-3.5
Particles with an aerodynamic diameter of _________________ required to reach deep lung.
1-5 microns
Particle size required for alveolar ducts and alveoli?
1-5 µm
Polymers in Controlled Release Dosage Forms: Diffusion - Membrane/Reservoir System (3)
1. A reservoir—whether solid drug, dilute solution, or highly concentrated drug solution within a polymer matrix—is surrounded by a film or membrane material (polymer). 2. The coating membrane controls the release of drug. 3. Nearly zero-order release kinetics
Gel Preparation (5)
1. API was mixed with co-solvent with part of the solvent 2. Polymer was added to the walls of the vortex solvent mix 3. API solution mix was added to the polymer solution mix 4. Neutralizer was added to the final solution mix 5. Gel formation after neutralization
Bioequivalence Criteria (4)
1. Ability of the product to achieve blood levels similar to the reference product 2. Administered to subjects under identical conditions 3. 90% confidence levels or 2 one-sided t-tests 4. Entire confidence interval (CI) must be between 0.8-1.25
Benefits of Oral: (2)
1. Absence of first pass metabolism 2. Sustained effect possible
If you don't want a drug to oxidize, you would... (2)
1. Add antioxidant 2. Add remaining space in ampule with Nitrogen gas
We choose polymeric materials as drug carriers based on three criteria:
1. Biocompatibility 2. Physical & Mechanical Properties 3. Pharmacokinetics Properties
Name 5 Biological Barriers
1. Biodegradation by digestive enzymes 2. Short in vivo half-life 3. Immunogenicity 4. Difficulty in crossing mucosal barriers 5. No access to some compartments
What are the 5 parts of the stomach?
1. Cardia 2. Fundus 3. Body 4. Antrum 5. Pylorus
What are the 2 methods that test HEPA Filters?
1. Challenge with monodisperse aerosol of dioctylphthalate (DOP) of 0.3 um diameter particles 2. Air velocity (< 70 ft/mt may indicate clogged filter)
Name 2 Chelating Agents (Minimize metal effects)
1. Citric Acid 2. EDTA
What are the 2 forms of aerosol filling?
1. Cold filling 2. Pressure filling
What are the 3 ways to prepare ointments?
1. Comminution 2. Incorporation 3. Fusion
Advantages of Solutions: (4)
1. Convenient for those unable to swallow solid dosage forms 2. Homogeneous doses which are easily adjusted 3. Drugs are absorbed in dissolved state 4. Can also be used externally
Name 4 things that could disrupt the absorption of a drug via oral administration?
1. Could precipitate in stomach/intestine 2. Decomposition could occur in stomach/intestine 3. First pass metabolism 4. If transporter required, saturation and/or competition is possible
Name 3 Controlled-Release Mechanisms:
1. Diffusion 2. Swelling followed by Diffusion 3. Degradation
3 Parts of Capsule formulation?
1. Diluents 2. Glidant 3. Lubricant *Water-proofing/surfactants
What are the 3 methods to purify water?
1. Distillation 2. Reverse Osmosis 3. Ion-Exchange Method
Controlled Release Dosage Form Disadvantages: (6)
1. Dose dumping 2. Delayed onset 3. Dependent on residence time in GI tract (some) 4. Loss of flexibility in adjusting the drug dose and/or dosage regimen 5. High cost of new technology 6. Risk related to regulatory approval
What are the 2 types of transdermal systems?
1. Drug Reservoir Membrane-Modulated Systems (Less Common) 2. Drug-in-Adhesive Diffusion-Controlled Systems (Matrix)
Disadvantages of Solutions: (4)
1. Drug may not be stable 2. Hard to do taste masking 3. Bulky and Heavy 4. Dose measurement can be inaccurate
Polymers in Controlled Release Dosage Forms: Diffusion - Matrix System (3)
1. Drug substance and a polymer excipient are mixed to form a homogeneous (matrix) system 2. Diffusion occurs when the drug passes from the polymer matrix into the external environment 3. Release rate decreases over time
Name 5 suitable drug characteristics for an Oral Controlled Release Dosage Form
1. Drugs with appropriate half-life (2-8 hrs.) 2. Drugs that are uniformly absorbed from GI tract 3. Drugs with small dose 4. Drugs with a good margin of safety 5. Drugs used in the treatment of chronic conditions
Layered tablets may be used for what reasons?
1. Extended release 2. Incompatible drugs separated by a buffer layer
3 Parts of Hard Gelatin Capsules?
1. Gelatin 2. Colorants 3. Opacifying Agents
Other commonly used solvents: (3)
1. Glycerin 2. Propylene Glycol (PG) 3. PEG 400
What are 4 characteristics of Fluid-Bed Granulation
1. Granulation and drying takes place in same equipment 2. Liquid is sprayed on suspended powders 3. Particle dried in suspended air 4. Equipment may be used for coating
Disadvantages of RDT's (2)
1. High Friability 2. Taste masking
Factors Affecting Gastric Emptying via the Duodenum Feedback Mechanism: (3)
1. Hydronium Ions 2. Osmotic Pressure Increase 3. Digestion products of fat
What are the 10 types of Compressed Tablets?
1. Immediate Release Tablets 2. Sugar-Coated Tablets 3. Film-Coated Tablets 4. Enteric-Coated Tablets 5. Layered Tablets 6. Press-Coated Tablets 7. Chewable Tablets 8. Controlled Release Tablets 9. Effervescent Tablets 10. Rapid-Dissolving Tablets
What 2 things can be done to increase solubility?
1. Increase temperature 2. Reduce Particle size
Oils can be administered via... (2)
1. Intramuscularly (IM) 2. Subcutaneously
Typically, a parental "suspension" is administered... (2)
1. Intramuscularly (IM) 2. Subcutaneously
Factors limiting oral absorption: (3)
1. Large molecule 2. Polar 3. Water-soluble
Multiple Compressed Tablets: (2)
1. Layered 2. Press-coated
Four main classes of polymers:
1. Linear 2. Cross-Linked 3. Branched 4. Dendritic
When does the FDA permit the importation of drugs? (4)
1. the drug is for personal use only 2. the quantity cannot exceed a 90-day supply 3. the buyer must be under medical supervision 4. the drug product cannot be imported for a commercial reason
Bacteriostatic WFI (Water for injection) is not packaged more than 30 mls because... (2)
1. to limit the # of entries 2. to not be given as infusion as mistake
Filter size to sterilize but with lipid
1.2 µm
Subcutaneous Amount
1.3 mL
How long is the large intestine?
1.5 meters
Normal Stomach (Fasting) pH:
1.5-2
For in vitro studies in Franz/static cells, the drug should not exceed _______ of its solubility in the receptor
10%
GI Motility (Fasting): Phase III
10-20 minutes Max Contraction, Housekeeper
When you don't have terminal sterilization what is the probability of contamination being present within the sample/preparation with filtration alone?
10⁻³ (1 in 1000)
Sod. Chloride Inj USP
154 mEq each of Sodium and Chloride
Dry Heat Sterilization (2)
160-170ºC for at least 2 hours 250°C for 30 minutes
How many valence for calcium?
2
IV bag will generally have _____ ports
2
Intramuscularly Amount
2-5 mL
Normal Stomach (Fed) pH:
2-6
GI Motility (Fasting): Phase II
20-40 minutes Increase in tone and activity
Particle size required for localized effects in trachea?
20-60 µm
Multiple use containers should generally be used within...
28 days
Weight of blank cocoa butter suppository?
2g
How many valence for aluminum?
3
GI Motility (Fasting): Phase I
30-60 min after meal Relaxation
What is 4 mEq of NaCl?
4 x 58.5 = 234 mg
Avoid coring in rubber closers by
45º bevel up
Low-risk CSPs are given a BUD of...
48 hrs at room temperature or 14 days under refrigeration
Normal Colon pH:
5.5-7
Manual examination past a light source with a black background can detect particles of about __________ size
50 μm
What is the molecular weight of NaCl?
58.5 mg
Aseptic handling must be a minimum of ______________ in the laminar flow hood
6 inches
Particle size required for respiratory bronchioles?
6 µm
Normal Duodenum pH:
6-6.5
Normal Ileum pH:
7-8
What is the molecular weight of KCl?
74.5 mg
HPLC: The peak at ____ minutes determines the drug
8
What is the HLB of a mixture of 75% Surfactant A (HLB = 8) and 25% Surfactant B (HLB = 12)?
8 x 0.75 (6) + 12 x 0.25 (3) = HLB 9 for the blend
HEPA filter flow rate
90 fpm +/- 20%
Dispersed System: Molecular Dispersion size:
< 1 nm
Up to what volume of liquid (water) will not change the motility pattern?
<~150 mL
If weight of cocoa butter blank suppository is 2 g, weight of medicated suppository is 1.8 g, and weight of drug incorporated is 200 mg, then what is the density factor (DF) of the drug for cocoa butter?
= 0.2/(2 - 1.8 + 0.2) = 0.2/0.4 = 0.5
Insoluble
> 10,000
Incorporation: Geometric Dilution
A technique used in mixing two ingredients of unequal quantities; one begins with the smallest quantity and adds an equal quantity of the ingredient having the larger amount. The process then continues until all of the ingredients are used. *Generally used for solids
Most generics are coded as...
AB, Therapeutically Equivalent meeting necessary requirements
Insulin adsorbed on Technosphere microparticles
AFREZZA insulin inhalation device
Rapid acting inhaled insulin device from MannKind Corporation
AFREZZA insulin inhalation device
Which CI is more definitive of the actual bioequivalence, Cmax or AUC?
AUC
Polymorphism
Ability to exist in more than one crystalline state/structure that may present different solubilities.
What's the main difference between the conclusive values of Absolute and Relative Availability?
Absolute cannot be greater than 1, while relative can be greater than 1.
Drug dissolved in GI Fluids → Drug in Blood
Absorption
Release from Delivery System/Dissolution → Drug in Blood
Absorption
Which process immediately precedes pharmacological effect?
Absorption
ADME stands for...
Absorption Distribution Metabolism Elimination
Occlusive (less than hydrocarbons) and emollient
Absorption bases
water in oil (w/o) emulsion or anhydrous bases that convert to w/o emulsion
Absorption bases
pH-Partition Theory: _________ are majorly absorbed in the stomach, while _________ are not.
Acids; bases
...transport can occur from a region of lower concentration to a region of higher concentration (i.e. against the concentration gradient)
Active
...transport process requires ATP energy
Active
How do you get a water in oil emulsion to not separate as readily?
Add a surfactant
_________________ must be compatible with the LVP
Additive
2nd Port from administration sets (bag)
Additive port
Which layer contains drug?
Adhesive Layer
1st port from administration sets (bag)
Administration port
__________________ are made under laminar flow hoods using strict aseptic techniques to maintain the sterility and freedom from particulates & pyrogens
Admixtures
What might happen if the MTC is below the Cmax?
Adverse Effects
What causes damage to the ozone layer?
Aerosol Propellants: Fluorinated hydrocarbons
extremely effective, relatively inert, nontoxic & nonflammable, e.g., dichlorodifluoromethane (Freon 12)
Aerosol Propellants: Fluorinated hydrocarbons
may be liquefied by cooling below their b.p. or by compressing the gas at RT
Aerosol Propellants: Fluorinated hydrocarbons
Nebulizer
Air stream produced manually or through compressed air source is used to break the drug solution into fine particles
Should not be used in pediatric formulations.
Alcohol
_______________ has preservative effect at concentrations greater than 15%
Alcohol
If 20 mL of a required HLB of 9.0 is needed, in what ratios should the available surfactants (HLBs 8 and 12) be mixed?
Allegation Alternate: 12 1 9 8 3 4 12: (1/4)(20) = 5 mL 8: (3/4)(20) = 15 mL
Primary structure
Amino Acid Sequence
Which is more water soluble? Amorphous or Crystalline?
Amorphous
_________________ molecules are best absorbed
Amphiphilic
NH+COO-
Amphoteric Surfactant
tip-seals (bead-seals) or pull seals
Ampuls
Drug
An active ingredient that is used to diagnose, cure, mitigate, prevent or treat a disease
Prodrug
An inactive drug dosage form that is converted to an active metabolite by various biochemical reactions once it is inside the body.
Dodecyl Gallate Octyl Gallate Propyl Gallate BHA BHT Vitamin E
Antioxidants
In retropulsion, what part of the stomach are particles of food sent back to?
Antrum
Would an anhydrous or hydrate form have higher solubility in water?
Anyhydrous
Intravenously amount
As much as needed
Parenterals Disadvantages (5)
Aseptic Techniques Tissue Toxicity Pain Error ? Medical Supervision
Association vs Aggregation
Association is generally reversible, while aggregation is not
Percutaneous Absorption Enhancers (8)
Azones Pyrrolidones Alcohols Surfactants Glycols Terpenes Fatty Acids Sulphooxides
The aqueous solubility of a weak base drug is poor. In an intubation study (drug perfused in the intestine), the drug was found not to be absorbed beyond the jejunum. Which of the following would be the best strategy to use to improve oral drug absorption of this agent? A. Give the drug as a suspension and recommend that it be taken on an empty stomach. B. Give the drug as the hydrochloride salt. C. Give the drug with an antacid. D. Give the drug in a suppository dosage form.
B. Give the drug as the hydrochloride salt. Explanation: Administration as the hydrochloride salt will help to ensure dissolution in the stomach without dependence on stomach acid for dissolution.
Viable Contamination
Bacteria
Sterile WFI containing one or more antimicrobial agents
Bacteriostatic WFI
Why is gastric emptying important for drug absorption?
Because some drugs may be degraded if left in the acidic environment of the stomach too long. Some drugs are not stable in the stomach So put an enteric coating on it.. 😐
Which is more water soluble? Anhydrous form or benzene?
Benzene
Imparts cohesiveness to the tablet formulation
Binders
e.g., (corn)starch, gelatin, povidone, natural and synthetic gums
Binders
Basic components of glycoproteins, amino acids, and sugar molecules
Biologic Agent
Broad specification; difficult to standardize
Biologic Agent
Complex physiochemical properties
Biologic Agent
Contamination possibility high, detection difficult, removal often impossible
Biologic Agent
Difficult to characterize
Biologic Agent
Heterogenous mixture
Biologic Agent
High molecular weight
Biologic Agent
Highly susceptible to slight changes in production process and environment
Biologic Agent
Lengthy, complex purification process
Biologic Agent
Many times antigenic
Biologic Agent
Sensitive to heat and shear
Biologic Agent
Through Biotechnology
Biologic Agent
Usually parenterally administered
Biologic Agent
Highly similar to the reference product notwithstanding minor differences in clinically inactive components, and has no clinically meaningful differences in terms of safety, purity, and potency (safety and effectiveness) from the reference product.
Biosimilar Product
Stepwise Approach to Demonstrating ______________________.
Biosimilarity
What is the rate limiting step for muscle or subcutaneous tissue?
Blood Perfusion
Blood Dialysis
Blood cells & plasma proteins fall in the colloidal size range and are retained, while impurities pass through the dialysis membrane
Type I Glass
Borosilicate *ampule(s)* (most inert)
Basic driving force of colloidal particles?
Brownian Motion
Where is Intensity located on a plasma concentration curve?
Btw the Cmax and MEC
Name an example of how excipients may affect drug solubility
Buffered Aspirin
IV admixture aka
CSP (Compounded Sterile Product)
Capping or splitting
Capping/splitting is a term used to describe the detachment of a cross-sectional fragment from the tablet face, which usually occurs just after ejection of the tablet from the die.
Indocin Rx: Gelatin
Capsule Shell
Which is more lipid soluble? Carbonyl or Alcohol?
Carbonyl
Ion-Exchange Method
Cation and Anion exchangers used successively or simultaneously to remove both cations and anions from water to make demineralized or deionized water
NH2+
Cationic Surfactant
Enteric-Coated
Cellulose acetate phthalate (Shellac) Special coating on drug that prevents absorption until drug reaches the small bowel by protecting it from acidic environments.
Brownian Motion
Chaotic kinetic movement of colloidal particles
Nutrient Content Claim
Characterize the level of a nutrient (free, high, low, reduced, etc) or describe % level of dietary ingredient for which there is no established Daily Value
Inert
Chemically inactive
Biological safety cabinet (BSC) is generally used for...
Chemo drugs
Irritation Testing uses a _____________________ to examine _________________________ _____________ __________
Chromameter; Transepidermal water loss
Laminar flow of HEPA-filtered air should meet _______________________, i.e., no more than ______ particles per cu ft of 0.5 μm and larger size. This is referred to as ISO (International Organization of Standards) _______________ specifications (no more than 3,520 particles per cubic meter) in USP <797>
Class 100 standards; 100; Class 5
Quaternary Structure
Cluster of two or more proteins
What are the 3 main parameters corresponding to drug absorption?
Cmax Tmax AUC
Increasing drug absorption rate causes... (3) Gabriel #2
Cmax increase Tmax not affected AUC increase
How does the plasma level-time curve change as the rate of drug absorbed increases?
Cmax: Increases Tmax: Decreases AUC: Not affected
How does the plasma level-time curve change as the amount/extent of drug absorbed increases?
Cmax: Increases Tmax: Not affected AUC: Increases
Example of suppositories that may need refrigeration?
Cocoa Butter
Melting Point: 30-36ºC/80-96.8ºF
Cocoa Butter
Shows marked polymorphism
Cocoa Butter
Triglyceride obtained from the roasted seeds of Theobroma cacao
Cocoa Butter
Suspension Advantages: (5)
For drugs which are not soluble in commonly used vehicles Many patients prefer a liquid form over a solid form Suspensions provide greater flexibility in the administration of doses A suspension can better mask the taste of a drug as compared to a solution Some drugs are chemically unstable when in solution but stable when suspended
Which form of Chloramphenicol is more unstable?
Form *B*
Sterilization by Ionizing Radiation
Gamma radiation from Cobalt-60 typically used; used for medical devices and hospital supplies
Identical or bioequivalent to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use.
Generic Drug
Composed of silicon dioxide with varying amounts of other oxides
Glass
Colloidal Silicon Dioxide
Glidant
Tablets: What allows powder to flow freely?
Glidant
e.g., fumed silicon dioxide
Glidant
Improve flow characteristics of powders
Glidants
e.g., colloidal silicone dioxide or talc
Glidants
______________ suppositories have been used for their laxative effect
Glycerin
Enforces Food Drug & Cosmetic Act
Government
Enforces standards set in USP-NF
Government
Monitors CGMP (Current Good Manufacturing Practices)
Government
Protect the public
Government
Inspection at least every two years
Government inspection for GMP
_____________________ is done so that powder can flow evenly & freely from the hopper into the dies
Granulation
Many variables; may alter the accuracy of the system
Gravity IV administration sets
Floatation is not used for __________ inhalers
HFA
What is the main difference btw hard and soft capsules?
Hard generally has 2 parts that come together in a locking groove manner, while soft is generally 1 continuous capsule
Saturated Solutions
Has dissolved the maximum amount of solute particles at a given temperature
What type of claim and is it allowed? "Chamomile product claiming it alleviates various disease states"
Health Claim that is NOT allowed
What type of claim and is it allowed? Ginseng product labeling states it possesses a "Powerful Anti-Cancer Function" and can prevent diabetes.
Health Claim that is NOT allowed
What type of claim and is it allowed? "Calcium may reduce the risk of osteoporosis"
Health Claim that is allowed
What type of claim and is it allowed? "Healthful diets with adequate folate may reduce a woman's risk of having a child with brain or spinal cord defects"
Health Claim that is allowed
What type of claim and is it allowed? "Soluble fiber, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease"
Health Claim that is allowed
FDA must authorize ___________ ____________ only before they are put in the label.
Health Claims
What type of claim and is it allowed? "Protects against heart disease"
Health claim that is NOT allowed
Flocculated Rate of Sedimentation
High
Electroporation
High voltage applied for a very short time
HDPE/LDPE/PP/PET
High/Low Density Polyethylene are used for ointment tubes *Low is more soft/flexible
Hard Gelatin Capsules: Under what conditions is gelatin soluble?
Hot water and warm gastric fluid
Largest single source of contamination
Humans/Personnel
typically, 2 to more than 60 mL; tuberculin syringes 1 ml
Hypodermic syringes
How can food affect absorption?
Influence on emptying
These do not depend on gravity; flow rates can be directly set, no need to count drops
Infusion Pumps
What does unfolding of a protein cause?
Internal hydrophobic molecules to become exposed to water
What are the biological barriers a drug must pass when going from: (3) Intratumoral → Target
Intratumoral → Tissue → Target
Parenteral Routes of Administration (4)
Intravenous Intramuscular Intradermal Subcutaneous
Rapid Action
Intravenous Route
Typically, inject into superficial veins in front of the elbow with aseptic precautions
Intravenous Route
Percutaneous Absorption
Involves the transfer of drug from the surface of the skin, through the different skin layers, and ultimately into circulation
Which form of a compound is more water soluble?
Ionized
________________________ is already used in physical therapy clinics for localized delivery of drugs such as corticosteroids
Iontophoresis
What type of osmotic solutions have the fastest gastric emptying?
Iso-Osmotic
Which would empty the duodenum faster, iso-osmotic or hyper-osmotic solutions?
Iso-osmotic
Why does steam sterilization work for aqueous formulations?
It generates its own steam
Gels
Jelly-like dispersions with the addition of a gelling agent
100 ml <
LVP
_________________________ are the major antigen-presenting cells of the skin
Langerhans cells
What is the major microflora component of the GI Tract?
Large Intestine
__________ ________________ has no villi
Large Intestine
Gastric Emptying of Liquids (Fed)
Large Volume placed into fed mode Begins immediately and continuously *First Order Rate*
Facilitative Therapy
Large amount of protein drug
must not contain bacteriostatic agents
Large volume parenterals (LVPs)
_________ side/supine posture decreases emptying.
Left
If the AUC decreased, what would that indicate?
Less drug was absorbed
Advantage of IM administration?
Less frequent administration due to sustained release
Colloid Properties: Optical:
Light scattering due to the Faraday-Tyndall Effect
How does a large amount of lipids affect drug absorption?
Lipids decrease drug absorption because they contain a high caloric density.
Only one form is stable; convert from unstable to stable form over time
Polymorph
Usually contain decongestants
Nasal Solutions
__________________ don't use propellants
Nebulizers
What is the terminology for a dietary supplement that was not on the market prior to October, 1994
New Dietary Ingredient
Sorption Examples: What can absorb in IV bags? (2)
Nitroglycerin and Insulin
Deflocculated Clear Boundary?
No
Flocculated Caking?
No
A metered dose inhaler is designed to deliver an asthma medication - Will it have a nebulizer?
No because it's a multiple dose
V = 1.0
No settling
"Can preservatives be added to a LVP?" If (yes/no), why?
No, because even though the % would be small, the volume would be too large.
Would you expect gentamicin to be absorbed well when given orally?
No, it's polar and large
Inert, non-irritating, non-toxic, miscible with body fluids - e.g, fixed vegetable oils or co-solvents
Non-Aqueous Vehicles
Which classification of surfactants are generally used most often in pharmaceutical dosage forms?
Nonionic
B
Not Therapeutically Equivalent
BN
Not Therapeutically Equivalent Aerosol Systems
BE
Not Therapeutically Equivalent Delayed-Release
BD
Not Therapeutically Equivalent Documented Problem
BS
Not Therapeutically Equivalent Drug Standard Deficiency
BC
Not Therapeutically Equivalent Extended-Release
BX
Not Therapeutically Equivalent Insufficient Data
BP
Not Therapeutically Equivalent Potential Problem
BR
Not Therapeutically Equivalent Systemic Suppository or Enema
BT
Not Therapeutically Equivalent Topical Product
B*
Not Therapeutically Equivalent and Needs Further FDA Review
AUC: Increased Rate
Not affected
Tmax: Increased Extent
Not affected
Suppository Advantages: (5)
Not exposed to harsh GI conditions Drugs irritating to stomach can be given Portal circulation is by-passed by ~50% Convenient when patient unable to swallow Effective in cases of vomiting
Hard Gelatin Capsules: How is gelatin obtained?
Obtained by partial hydrolysis of collagen via animals
Rancidity
Oil goes bad
Emulsions: oleaginous internal phase and an aqueous external phase
Oil/Water (o/w)
Cetyl Alcohol
Oleaginous Component
Stearyl Alcohol
Oleaginous Component
White Petrolatum
Oleaginous Component
Anhydrous (no water); difficult to wash off (2)
Oleaginous or Hydrocarbon Bases Absorption Bases
Good occlusive, emollient properties
Oleaginous or Hydrocarbon bases
Petrolatum alone
Oleaginous or Hydrocarbon bases
Petrolatum modified by waxes or liquid petrolatum (mineral oil)
Oleaginous or Hydrocarbon bases
Titanium Dioxide
Opacifying Agent
What might explain different absorption at different regions within the small intestine?
Openings (pores) are smaller in the Ileum compared to the jejunum
What are the biological barriers a drug must pass when going from: (5) Oral/Transdermal → Target
Oral/Transdermal → Skin Mucosae Epithelium → Blood Vessels → Tissue → Target
What has a feedback mechanism?
Osmotic Pressure
Picking and Peeling (sticking)
Over-wetting or examples or excessive film tackiness causes tablets to stick to each other or to the coating pan. On drying, at the point of contact, a piece of the film may remain adhered to the pan or to another tablet, giving a "picked" appearance to the tablet surface and resulting in a small exposed area of the core.
RODAC (Replicate Organism Detection and Counting)
Overfilled convex surface with surfactant
What is a plasma membrane protein that acts as a localized drug transport mechanism, actively exporting drugs out of the cell?
P-Glycoprotein
Ointment Compendial Requirements: Products applied topically should be free of _____________________ & _____________________
P. aeruginosa; S. aureus
Permeability =
PDA/h
Soft capsule excipient(s)?
PEG 400, PG, and
A lipophilic drug formulated into a cocoa butter suppository is failing to exert its therapeutic effect - what could be the possible reason?
PEG should be used instead of Cocoa Butter for more sustained release of drug
Changes in Lipid Solubility doesn't affect absorption rate during...
Paracellular Passive Diffusion via pores/channels
Petroleum: Solid Hydrocarbons
Paraffin Wax
What is a defining characteristic of crossover studies determining bioequivalence of 2 or more drugs?
Participants serve as their own control via a 3 step process: 1. Randomly taking drug or placebo 2. Crossover (washout) 3. Taking drug that wasn't taken in 1st step
Microparticles
Particles with a size comprised between 1 and 100 μm
P =
Partition coefficient, measure of lipid solubility
Drug slowly passes through membrane so the ___________________ is the rate limiting step.
Passage through the membrane
What is the most common process or mechanism at which drugs cross the membrane?
Passive Diffusion
Zinc Oxide is generally what type of Ointment?
Paste
Ointments: ____________ consist of a large percentage of solid/"stiff" material
Pastes
Can an IV admixture be prepared by extracting the drug aseptically from a patch? Explain.
Patch is not sterile
Self-administration of analgesics in proportion to degree of relief desired
Patient-controlled Analgesia (PCA)
Used to control postoperative pain for a variety of surgical procedures
Patient-controlled Analgesia (PCA)
Ensure that medicines have appropriate labeling and instructions regarding their use
Patients
Examine physically and visually the medicines they receive to ensure that they have received the correct product in the right strength with a current expiry date
Patients
Obtain pharmaceutical agents only from authorized or licensed sources
Patients
Cmax
Peak plasma concentration achieved from 1 dose of a specified drug
Subcutaneous Rate-Limiting Step?
Perfusion
Size, density, shape, charge Velocity, Device, Pattern, Dose, Drug properties
Pharmaceutical Factors Affecting Particle Deposition
Develops a procedure for product selection that includes evaluation of quality
Pharmacist
Develops a recall procedure
Pharmacist
Have expertise about the composition of drug products, including their chemical, biological, and physical properties and their manufacture and use
Pharmacist
Drug Quality and Security Act of 2013
Pharmacists may register with the FDA as human drug compounding outsourcing facilities Must be inspected by the FDA May sell compounded products to hospitals, doctors, other pharmacies, etc. without a prescription for a specific patient
Stepwise Approach to Demonstrating Biosimilarity: 3. Human Studies: (2)
Pharmacokinetics, Pharmacodynamics
Bile secretion is during which phase of fasting gastric motility?
Phase 2
Most emptying happens during which phase?
Phase 2
At what phase of the MMC will an enteric-coated tablet be emptied during the fasting stage? Jessica #1
Phase 3
If a patient takes an enteric-coated tablet on a full stomach, in what phase of the MMC will the tablet leave the stomach? Anna #3
Phase 3
When do enteric coated tablets empty the stomach?
Phase 3
When would an enteric coated tablet/capsule exit the stomach during the fasting state?
Phase 3
Mucous Discharge is during which phase(s) of fasting gastric motility?
Phase 3 & 4
_______________ instability can be minimized by using appropriate excipients (salts, sugars, amino acids, and glycerol) that protect the molecule
Physical
Chirality
Physical/Chemical Properties of Drug (API)
Crystal Properties
Physical/Chemical Properties of Drug (API)
Particle Size
Physical/Chemical Properties of Drug (API)
Provide ease of use, e.g., for biotech-based drugs
Prefilled Syringes
Reduced risk of misidentification, dosage error, and contamination
Prefilled Syringes
Benzoic Acid Sodium Benzoate (Methyl/Propyl)Parabens
Preservatives
Parabens
Preservatives
Protect against microbial contamination
Preservatives
e.g., phenylmercuric nitrate, thimerosal 0.01%, benzalkonium chloride 0.01%, phenol or cresol 0.5%
Preservatives required in *multiple-dose SVP* containers
________________ filling is used for most pharmaceutical aerosols.
Pressure
Valve first then product
Pressure filling
Goals to be achieved in Handling of Cytotoxic & Hazardous Drug (4)
Prevent *accidental* contamination Prevent contamination during *preparation* Prevent contamination during *administration* Prevent contamination of *environment*
An immediate use CSP is a low risk preparation made outside a ________ and is intended for...
Primary Engineering Control (PEC); emergency use and administration must begin no later than 1 hour following the start of the preparation of CSP; otherwise discard.
Fusion
Process of heating and cooling
Iontophoresis
Process of infusing water-soluble products into the skin with the use of electric current, such as the use of the positive and negative poles of a galvanic machine.
PA
Prolonged Action
What cannot be autoclaved and why and what can be done instead?
Protein formulation; because it will destroy/denature the protein(s); filter sterilize through a 0.2 micron filter because 0.2 micron filter will remove all bacteria
On a molar basis, what takes the shortest amount of time to be emptied from the stomach? Fats, Proteins, or Carbs?
Proteins
What cannot pass through skin (Stratum Corneum)
Proteins
What is the main objective for when an ANDA is submitted?
Proving safety and efficacy
Before Injection
Psychological
__________ _____________ is used when filling a small number of capsules
Punch Method
______________ water must be used for solutions
Purified
Which part of the stomach regulates food dumping?
Pylorus
Why is multiple distillation required to sterilize/purify water?
Pyrogens aren't volatile therefore they require multiple distillations to be eliminated completely. Sorta vague but go off..
Pyrogen Testing Methods (2)
Rabbit test or the more recent LAL test (USP Bacterial endotoxins test)
Advantages for Inhaled Drugs: (3)
Rapid onset Reduced dosage & side effects Avoids first pass metabolism
Gastric Emptying of Solids (Fasting)
Rapidly Dissolving Drugs - Empty as bolus
Bioavailability depends on... (2)
Rate & Extent
Examples include suppositories for pain, migraine, or for tranquilizers; or for local action as cathartic or hemorrhoidal suppositories
Rectal Suppositories
Typically: •1½" •Cylindrical •Tapered •2 g if cocoa butter base •Systemic & local
Rectal Suppositories
A product approved by the FDA under the Public Health Service Act based on a full complement of data, including non-clinical and clinical data.
Reference Product
The single biological product
Reference Product
FDA designates this product
Reference Product (Innovator)
Holder of NDA
Reference Product (Innovator)
Intensity
Related to the number of receptors with which the drug interacts
If the drug is in a solid dosage form → Drug crystals exposed to GI fluids
Release
Protective Liner
Release
Reservoir Patch
Release membrane may be prepared from a co-polymer of ethylene acetate with vinyl acetate
Drug Supply Chain Security Act
Requirements for tracing prescription drug products through pharmaceutical supply distribution chain.
Reseals as soon as the needle is withdrawn to allow multiple entries
Rubber closures
Steam Sterilization
Saturated steam under pressure (121ºC for 15 min) in autoclave
Topical Dosage Forms
Semisolid dosage forms intended for topical application to skin or mucous membranes
Deflocculated State of Particles:
Separate entities
Stomach Function(s):
Serves as a reservoir Secretion of: acids, mucous, proteases, hormones, intrinsic factor (Vitamin B12) Mixes bolus with gastric secretions Digestion: hydrolysis, churning Absorbs alcohol and some acidic/weakly basic drugs Bacteriostatic
____________ __________ is a 85% solution of sucrose in purified water
Simple Syrup
For a weak acid, would the percentage of unionized change when exposed to a more acidic environment? If so, how would it change?
Since the compound is a weak acid, it would become more unionized (more protonated) as the pH of the environment into which it is placed decreases (i.e., the environment becomes more acidic).
Can be used only for newtonian liquids
Single point instrument, e.g., capillary viscometer
Minimally invasive technique to create micron sized temporary transport pathways
Skin Microporation
In-Vitro Franz Cell Setup
Slide 21
Deflocculated Rate of Sedimentation
Slow
Chemically synthesized
Small Molecule Drug
Completely characterized by analytical methods
Small Molecule Drug
Contamination can be generally avoided, is easily detectable and removable
Small Molecule Drug
Easy to purify
Small Molecule Drug
High, well-established purity
Small Molecule Drug
Low molecular weight
Small Molecule Drug
Not affected by slight changes in production process and environment
Small Molecule Drug
Relatively uncomplicated chemical structures
Small Molecule Drug
Single entity
Small Molecule Drug
Stable
Small Molecule Drug
Usually non-antigenic
Small Molecule Drug
Various routes of administration
Small Molecule Drug
Well-defined physiochemical properties
Small Molecule Drug
Explain the bioavailability of small drug molecules.
Small molecules have a higher bioavailability due to their ability to dissolve more completely in solution.
Why does smaller particles have more surface area and consequently a faster rate of absorption than larger particles?
Small molecules have a higher bioavailability due to their ability to dissolve more completely in solution.
Why are eye ointments in small tubes?
Small tip for application
Type III Glass
Soda Lime *Mainly for Dry Formulas*
Ringer's Ejection composition and purpose
Sodium Chloride/Acetate Potassium Chloride Calcium Chloride *Source of Electrolytes
_________ lenses use a hydrogel such as hydroxyethyl methacrylate (HEMA)
Soft
Usually prepared, filled & sealed in a continuous operation
Soft Gelatin Capsules
Piggyback IV administration:
Solutions from two containers flow into the patient veins through a common tubing and a common injection site
Hydrate
Solvate that contains water
As much as 85%; e.g. room deodorizer (Fine particles)
Space sprays
_____________ and _____________________ issues generally dictate parenteral administration
Stability; bioavailability
When would a liquid begin emptying in the fed mode?
Starts Immediately due to being a liquid
Moist heat causes denaturation of proteins
Steam Sterilization
Primarily used as a check test
Sterility Test
What percentage of sulfaethidole is *unionized* at pH 6.5? The pKa of the compound is 5.5
Sulfaethidole is a *weak acid* due to the SO₂ group stabilizing the nitrogen atom via resonance. pH = pKa + log([Base]/[Acid]) BASE/ACID = (S⁻)/(HS) = 10^(pH-pKa) ∴ at pH = 6.5 (S⁻)/(HS) = 10^(6.5-5.5) (S⁻)/(HS) = 10¹ (S⁻)/(HS) = 10 This means that there are 10 "parts" in the ionized (or base form) and 1 "part" in the unionized (or acid form). The percentage unionized would be estimated as the number of "parts" in unionized form divided by the total number of parts. % Unionized = ((1)/(1+10))•100 *% Unionized = 9.1%*
these are effective at low levels, e.g., croscarmelose (Ac-Di-Sol), crospovidone (Polyplasdone), or sod starch glycolate
Super Disintegrants
Only 0.1% of Rx/OTC products in U.S.
Suppositories
Solid dosage forms intended for insertion into body orifices
Suppositories
preferred for infants or those who cannot take medications orally
Suppositories
A =
Surface Area
Dermatological Spray aka
Surface Spray
Association or Amphiphilic Colloids aka...
Surfactant
Potassium Laurate
Surfactant
Amphiphilic nature - adsorb at interfaces
Surfactants
Surface active agents have a certain affinity for both polar & nonpolar solvents
Surfactants
SA
Sustained Action
SR
Sustained Release
Polymers in Controlled Release Dosage Forms: Swelling-Controlled Release System:
Swelling-controlled release systems are initially dry and, when placed in the body will absorb water or other body fluids and swell. The swelling increases the aqueous solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into the external environment.
Plastic or glass - single use disposables, packaged as a sterile unit
Syringes
______________ are usually prepared by compression of the drug with several excipient
Tablets
Tape Stripping
Technique used to determine an adhesives effect on the permeability of the stratum corneum
How to liquify a gas?
Temperature or pressure
Autoclaving aka...
Terminal Sterilization
Line drawings in open, pre-closed, and closed positions
The Coni-Snap Capsule
Frequency of Administration
The Therapeutic Objective
Local Action
The Therapeutic Objective
Rapid/Prolonged Effect
The Therapeutic Objective
Tmax
The amount of time it takes for the drug to reach Cmax
Reverse Osmosis
The application of pressure on a solution to cause water molecules to flow through a semipermeable membrane from a more-concentrated to a less-concentrated solution
Narrow Therapeutic Index
There is less than a 2-fold difference in median lethal dose and median effective dose values for a drug product or there is less than a 2-fold difference in the minimum toxic concentrations in the blood and minimum effective concentrations in the blood, so safe and effective use of the drug product requires careful dosage titration and patient monitoring
What is the purpose of a Drug Delivery System?
These systems are exploited for therapeutic purpose to carry the drug in the body in a controlled manner from the site of administration to the therapeutic target
Bridging
This occurs when the coating fills in the lettering or logo on the tablet
Duration
Time that drug remains above the MEC (Minimum Effective Concentration)
Onset Time
Time when therapeutic response is first observed
TR
Timed Release
Hard Gelatin Capsules: Opacifying Agent
Titanium Dioxide
The length of time it takes to get to the Cmax value?
Tmax
What is the goal of mixing and blending?
To produce a homogeneous mixture
Preservative Efficacy Test is used so that...
To test the presence of microbial growth over time
Stepwise Approach to Demonstrating Biosimilarity: 2. Animal Studies: (4)
Toxicity, Pharmacokinetics, Pharmacodynamics, and Immunogenicity
Which is the quickest pathway of absorption for a drug?
Transcellular
For pathways of absorption, what type of diffusion are most oral drugs absorbed?
Transcellular Transport
Most passive diffusion occurs via
Transcellular diffusion
_________________________ was the first transdermal product
Transderm-Scop
(T/F?) There are dietary supplements on the market that may intentionally and/or unintentionally contain ingredients that can cause health problems
True
Immediate/Extended Release
Type of Product
The _________________ classifies CSPs as low, medium or high-risk according to the corresponding probability of contamination.
USP <797>
Advantages of plastics? (3)
Un-breakable Not heavy No air interchange required
Suspensions: Desirable Features: (3)
Uniform dispersion or settle slowly & redisperse easily Particle size of suspended solid should remain fairly constant over long periods of standing Suspension should pour readily and evenly from its container
Flocculated Appearance
Unsightly
Typically: •Bougies •Slender, pencil-shaped
Urethral Suppositories
Administered by applicator for erectile dysfunction
Urethral Suppository: Alprostadil
Drug suspended in PEG 1450 to form a microsuppository
Urethral Suppository: Alprostadil
Single use for delivery to male urethra
Urethral Suppository: Alprostadil
___________ is a direct way of telling us how much drug was absorbed
Urine
Stokes equation
Used to identify particle size
Supersaturation Effect
Using a designated amount for prescribed medication delivery, rather than just slathering it on as you please like moisturizing lotion
Typically: •Pessaries •Globular, oviform, or cone-shaped •5 g if cocoa butter base
Vaginal Suppositories
Often buffered to an acidic pH
Vaginal Suppositories & Inserts
Progesterone suppositories with micronized powder in PEG base often compounded - tailored to meet individual needs
Vaginal Suppositories & Inserts
Typically, for candida infections, dryness or contraception
Vaginal Suppositories & Inserts
Vaginal tablets/inserts replacing many vaginal suppositories
Vaginal Suppositories & Inserts
Nystatin
Vaginal Suppository/Insert
oil/water Cream
Vanishing
Stearate Creams aka
Vanishing Cream
Name an example of a non-medicated ointment.
Vaseline
rubber closure (stopper) held in place by aluminum caps
Vials
HPMC Methyl Cellulose
Viscosity and Thickening Agents
How are the plasma level vs time curve parameters determined?
Visually from the graph
What type of absorption base is Lanolin, USP?
W/O Emulsion
Sterile Water for Injection USP
WFI sterilized & packaged in single dose containers of NMT 1 L size
PEG (400/1500/3350)
Water Soluble Components
Cold cream is a...
Water in Oil (w/o) Emulsion
Easily wash off
Water-removable bases
Example of suppositories that generally don't need refrigeration?
Water-soluble PEG
"Greaseless" bases with water-soluble components
Water-soluble bases
Polyethylene glycol ointment, NF
Water-soluble bases
Emulsions: aqueous internal and an oleaginous external phase
Water/Oil (w/o)
Advantage of subcutaneous administration?
We can train patients to self-administer
What drugs can exists as salts? (2)
Weak Acids and Weak Bases
Wet vs Dry Granulation
Wet: Powder is treated w/ Binder Dry: Powder skips treatment w/ binder
Sterility Assurance Level (SAL)
What confidence do we have that there will be no contamination after sterilization
Stoke's Law
When any object rises or falls through a fluid it will experience a viscous drag
Petroleum: Semisolid Hydrocarbons
Yellow Petrolatum = Petroleum Jelly/Vaseline
A metered dose inhaler is designed to deliver an asthma medication - Does it have to be sterile?
Yes
Deflocculated Caking?
Yes
Flocculated Clear Boundary?
Yes
A metered dose inhaler is designed to deliver an asthma medication - Will it have a preservative?
Yes because it's multiple
What is the rate of reaction for solids emptying into the small intestine? Robert #2
Zero order
Increased amount of acid may give...
a better taste
Lyophilization
a combination of freezing and drying; used to preserve microorganisms and other cells in a viable state for many years
The term "new dietary ingredient" means...
a dietary ingredient that was not marketed in the United States in a dietary supplement before October 15, 1994.
Repeat Action Dosage Forms
a dosage form usually containing two single doses of medication, one for immediate release and the second for delayed release.
USP Injection monographs provide...
a limit for bacterial endotoxins
Coarse dispersions with particles (> 0.5 µm; typically 1-50 µm) are dispersed in...
a liquid medium
Diffusion is...
a series of random steps a molecule takes as it moves from where it started, which is generally an
Cardia
a small space at the very entrance to the stomach that sits just under the diaphragm and the heart. It is so named because of its proximity to the heart.
Luer-Lok syringe
a syringe for injection having a simple screw lock mechanism that securely holds the needle in place
Quality assurance is...
a systematic method to identify problems in patient care that are resolved via administrative, clinical, or educational actions to ensure that the final products and outcomes meet applicable specifications.
Select all that apply regarding the small intestine: a. Efflux transporters span the entire length b. The same efflux transporters span the entire length c. Specific metabolic enzymes are present at different sites of the small intestine d. Most drug absorption occurs in the small intestine
a. Efflux transporters span the entire length c. Specific metabolic enzymes are present at different sites of the small intestine d. Most drug absorption occurs in the small intestine
Which of the following does Parietal cells secrete? Select ALL that apply: a. HCl b. Intrinsic Factor c. Mucous d. Pepsin
a. HCl b. Intrinsic Factor
Which factors increase gastric emptying? Select ALL that apply. a. Iso-osmotic solutions b. stress, anxiety, depression c. Lying on your right side d. Being male e. Aggression
a. Iso-osmotic solutions c. Lying on your right side d. Being male e. Aggression
What will happen to the pressure in an aerosol container as some product is released when (a) a propellant is used (b) when a compressed gas is used
a. Liquid Propellant maintains homeostasis therefore, pressure remains constant b. Pressure decreases
Select all that apply: What are the factors that blood flow has on absorption? a. Perfusion rate b. Diffusion rate c. Osmolarity d. pH effect on rate
a. Perfusion rate b. Diffusion rate
Select all that are true about passive diffusion? a. natural tendency of molecules to move from higher to lower concentration b. result of random kinetic movements in a medium c. it is not energy dependent d. requires the use of carriers e. driven by a concentration gradient
a. natural tendency of molecules to move from higher to lower concentration b. result of random kinetic movements in a medium c. it is not energy dependent
Select all the factors that decreases gastric emptying? a. small volume of liquid on an empty stomach b. depression c. small volume of liquid on a fed stomach d. low caloric intake e. low hydronium ion concentration
a. small volume of liquid on an empty stomach b. depression d. low caloric intake
Nernst Potential aka... location?
absolute charge on the surface
Intrinsic factor is responsible for
absorbing B12
The more lipid soluble, the better the _________________.
absorption
Log ka =
absorption rate
Zeta Potential aka... location?
actual charge 1 parameter away from surface
High First Pass Metabolism makes good candidates for ________________.
aerosols
Cloudiness indicates that the solution has...
aggregated (not good)
What emotional state(s) increase emptying?
aggression
A product is deemed to pass sterility test if...
all media vessels incubated with product sample reveal no evidence of microbial growth (turbidity)
Biologics Price Competition and Innovation Act of 2009
amends the Public Health Service Act (PHS Act) to create an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product.
Disinfect ______________ before opening
ampules
Cold Cream: Wax (Free Fatty Acid) + Sodium Borate =
an emulsifying agent
Press-coated tablets consists of...
and inner and outer layer
Ointments Compendial Requirements: All emulsions require a(n)...
antimicrobial agent
Surfactant
any substance that interferes with the hydrogen bonding between water molecules and thereby reduces surface tension
Biotechnology
any technique that uses living organisms in the production or modification of products.
Oxygen and nutrients are transported to nonvascular areas by...
aqueous humor
You "heat" __________________ components but "melt" __________________ components prior to combination.
aqueous; oleaginous
For CSPs, media fills should be performed...
at least annually (semi-annually for high-risk CSPs) for each person authorized to compound.
Which of the following disease states will increase gastric emptying? Select ALL that apply. a. Hypothyroidism b. Cholecystitis c. Hyperthyroidism d. Gastric Ulcer e. Duodenal Ulcer
b. Cholecystitis c. Hyperthyroidism e. Duodenal Ulcer
2. Which one does not belong with the other? a. Stomach (fasting) : pH 1.5-2 b. Duodenum : pH 2-3 c. Ileum : pH 7-8 d. Colon : pH 5.5-7
b. Duodenum : pH 2-3
Transcellular transport with intracellular metabolism will typically do which of the following? a. Increase bioavailability b. Reduce bioavailability c. No change d. None of the above
b. Reduce bioavailability
Which of the following is true? a. Metabolism does not alter the drug while excretion does. b. Both Metabolism and excretion alter the drug. c. Metabolism alters the drug while excretion does not. d. Neither metabolism or excretion alter the drug.
c. Metabolism alters the drug while excretion does not.
Select ALL that are consider Pro-Kinetic Drugs: a. Isoniazid b. Oxycontin c. Methoclopramide d. Mylanta e. Aspirin
c. Methoclopramide
Why is gastric emptying important for drug absorption? a. The stomach is the primary place for absorption b. There are abundant carriers in the stomach c. Some drugs are not stable under acidic conditions of the stomach d. None of the above
c. Some drugs are not stable under acidic conditions of the stomach
Which of the following factors can be the rate limiting step of drug absorption? a. Blood Perfusion b. Membrane Permeability c. Both d. Neither
c. both
What effect does increased rate have on Cmax and Tmax? a. increase, increase b. decrease, increase c. increase, decrease d. not effected, decrease Aparna's #3
c. increase, decrease
HLB values are additive, so surfactants...
can be blended
Macronutrients
carbohydrates (dextrose) proteins (amino acids) fats (lipids)
Fast injection of K+ will cause...
cardiac arrest
Metabolism
chemical change of a drug within the body
Mannitol is generally found in _____________ tablets
chewable
HFA's don't contain _________________ therefore they don't deplete the ozone layer
chlorine
Duragesic (fentanyl) is used for ________________ pain
chronic
Sugar coated tablets are generally ____________.
circular
Rack loading washers can be used to...
clean ampuls/other containers
What must happen to produce a generic for a topical?
clinical trials, which is a taskkkkk because skin is involved rather than just blood
Film-coated
coated with thin layer of water-insoluble polymer
Ion-Exchange Resins are modified by...
coating with a polymer barrier
Prefabricated dosage forms may be used for
compounding for special needs when bulk drug is not available, e.g., uncoated tablets or capsules
Mottling
condition of spotting with patches of color
Miotics
constrict pupils
Controlled Release Dosage Forms (CRDF) release drug in a...
controlled manner at a predetermined rate, duration, and location, to achieve desired therapeutic outcomes
Due to short half-lives, __________________ ______________ parenteral administration desired if possible, e.g., microspheres
controlled release
Gels are not...
cross-linked
Contact Lenses are...
cross-linked hydrogels
What must occur in order for a systemic effect from a drug to be observed? a. Elimination b. Metabolism c. Digestion d. Absorption
d. Absorption
Gastric emptying is generally faster for which source(s) of nutrients, assuming the same caloric value? a. Fats b. Proteins c. Carbohydrates d. All are the same e. None of the above
d. All are the same
Which of the following does NOT affect gastric emptying? a. Volume of liquid b. Caloric Value c. Emotional state d. All of the above affect gastric emptying
d. All of the above affect gastric emptying
How long does it take for an enteric coated tablet to dissolve in the stomach? a. 30 seconds b. 15 minutes c. 60 minutes d. None of the above
d. None of the above
Fick's First Law of Diffusion
dC/dt = (PDA/h)•(C(AD) - C(P))
An increase in [H+] in the duodenum will _________________ stomach emptying
decrease
Pathways of Intestinal Absorption: If a drug interacts with a P-Glycoprotein would ______________ the bioavailability of the drug because...
decrease; because it inhibits the amount of drug molecules allowed into the cell
Vigorous exercise increases or decreases emptying?
decreases
Denaturation
defined as any modification of secondary, tertiary, or quaternary structure of the protein molecule. It is a process by which hydrogen bonds, hydrophobic interactions, and salt linkages are broken, and the protein goes from its native, folded state to an unfolded chain with no specific three-dimensional structure
Polymers in Controlled Release Dosage Forms: Biodegradable system Degradation:
degrade within the body as a result of natural biological processes, therefore eliminating the need to remove a drug delivery system after release of the active agent has been completed. *Hydrolysis *Polymer-controlled
Aerosolization generates excessive air/water interfaces, which may lead to __________________ or ____________________
denaturation; aggregation
Modified Release Dosage Forms
describe dosage forms having drug release features based on time, course and/or location that are designed to accomplish therapeutic or convenience objectives not offered by conventional or immediate-release forms. So modified release is a very general term to describe any dosage form which can achieve some useful features or objectives not offered by traditional dosage forms. However, on USP monograph, modified-release forms just include extended release and delayed release.
2 in 1
dextrose (carbs) amino acids (proteins)
3 in 1 (TNA)
dextrose (carbs) amino acids (proteins) lipids (fats)
C(AD) - C(P) =
difference in concentration across membrane
Polymorphs Different solubilities =
different absorption rates
Mydriatics
dilate pupils
Potassium preparations must be...
diluted and given by slow i.v. infusion
Formulation of Suspensions: First step:
disperse particles in dispersion medium and make sure that they are wetted properly by adding surfactant
Very insoluble drugs whose availability is controlled by ____________________ may not benefit from formulation in controlled release forms
dissolution
The receptor/drug interaction...
doesn't physically alter the drug molecule.
Irritation Testing: Animal
draize dermal irritation test on rabbits
Controlled release dosage form (CRDF) is a dosage in which the...
drug release kinetics is predictable and reproducible from one unit to another.
Transscleral iontophoresis
drug targeting to posterior segment of the eye
Stinging in the eye
dry eye
Which of the following would *decrease* when a drug is more rapidly absorbed? a. AUC b. Efficacy c. Cmax d. Potency e. Tmax
e. Tmax
Manufacturer does not have to prove to FDA that their product is ______________ but they are limited to the...
effective; health claims, nutrient content claim, and function claim that they can make.
What is the major concern when functional groups are modified..
effectiveness
Increasing concentration will generally ______________ delivery but the driving force is provided by ________________________ activity, which also depends on the vehicle as solubility will change if vehicle is changed.
increase; thermodynamic
PEGylation of Proteins results in ______ half life, _______ proteolysis, and __________ immunogenicity.
increased; reduced; decreased
Aggregation increases as the concentration of protein in solution _______________.
increases
As the lipid solubility increases, the rate of absorption _______________.
increases
Increasing osmolar pressure _______________ gastric emptying.
increases
Moderate exercise increases or decreases emptying?
increases
Right side posture ________________ emptying.
increases
Packaging and Storage: Typically, cocoa butter suppositories are...
individually wrapped in foil or plastic or placed in divided cardboard box
What increases production for rotary presses?
induced dye feeders
Dietary Supplement manufacturers must provide FDA with...
information that their product will "reasonably be expected to be safe"
Reference product is the...
innovator
disintegrate is used so that it can be dissolved _____________ the body while binding agent is used so that it doesn't dissolve ______________ the body.
inside; outside
Large volume parenterals (LVPs) intended for...
intravenous (IV) infusion
Suspensions cannot be be given _____________________
intravenously
Excessive heating of syrups may produce...
invert sugar
A basic drug in an acidic environment would generally be in a more _____________ form
ionized
A basic drug would be more __________________ at the low pH of the stomach.
ionized
Dietary Supplement
is a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary supplement used by man *or woman* to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E).
Microdialysis Sampling
is based on the diffusion of non-protein-bound drugs from interstitial fluid across the semipermeable membrane of the microdialysis probe
Nasal solutions are ______________ to nasal fluids and buffered to approximate the normal pH range of nasal fluids, which is...
isotonic; 5.5-6.5
Lyophilic systems
just by dissolving in water, e.g., gelatin, acacia, albumin, insulin etc. "Loves the solvent"
Basal layer has ___________________ and other specialized cells such as ________________ and ____________________ cells
keratinocytes; melanocytes; langerhans
Passive Diffusion is driven by
kinetic energy
What is the driving force for passive diffusion?
kinetic energy
Hard capsule excipient(s)?
lactose
Body
large central portion of the stomach Primary area of digestion and where HCl acid and pepsin begin to digest food
Protein drugs are generally made by...
large-scale cultivation of genetically engineered "host" cells; rapidly growing cells with artificially inserted genes that encode the protein being made.
Vaginal suppositories are generally _____________ than Rectal suppositories
larger
Kel is determined using...
last two concentration values collected (Cp1 and Cp2) at time t1 and t2
Very Soluble
less than 1
Drugs with biological half-life's ________________________________________________ are viewed as questionable candidates for controlled release formulations.
less than one hour or greater than 12 Hrs.
Solids empty in a ______________ fashion, i.e., following ________-order kinetics.
linear; zero
Log P or D aka...
lipid solubility
Carbonyl groups make a molecule more...
lipid soluble
The higher the partition coefficient (log P or D), the more...
lipid soluble
Passive delivery only works for...
lipophilic (moderately) uncharged drugs with low MW, which are potent (low dose), need continuous delivery, and have short half-life and a wide therapeutic window; components, formulation & drug must be non-irritating & non-sensitizing
Aerosols depend on the power of...
liquefied or compressed gas to disperse the active ingredients in a finely dispersed mist, foam, or semisolid
Metered dose inhalers and nebulizers are _______________ inhalers
liquid
pH-Partition Theory: Which is more lipid soluble? non-ionized or ionized
non-ionized
Facility Design: Ceiling & floor
non-porous, non-shedding material; curved interfaces & flush-mounted recessed fixtures
Increasing hydronium ions (decreasing pH) would cause a shift toward the __________________ form of the drug.
nonionized
Total Parenteral Nutrition (TPN)
nutrient-complete solution given directly into bloodstream when person cannot eat by mouth
HLB 9-12
o/w
A soft gelatin capsule contains a drug dissolved in vegetable oil. You are asked to dispense a prescription for which you extract this drug from the softgel by cutting it open and squeezing the contents into a graduate. Which of the following dosage forms can then be prepared to administer this to the patient in (at least somewhat) palatable (acceptable taste) form: a. solution b. o/w emulsion c. w/o emulsion d. none of the above
o/w emulsion
convenient way of oral administration
o/w emulsion
How is pore closure delayed?
occlusion
Under-filled method
one bag is filled with half of only one thing
Medication should be taken at least...
one hour before retiring
Newtonian curve requires
one point
pH-Partition Hypothesis
only the non-ion form of a molecule may passively diffuse across cell membranes
Endotoxins
or bacterial pyrogens, are the natural complex of lipopolysaccharides from the outer layer of gram negative bacteria, or the dead microorganisms themselves, causing a pyretic and other pathogenic responses upon injection
pH-Partition Theory: What determines degree of ionization? (2)
pH (variable) and pKa (fixed)
Packaging and Storage: Glycerin or glycerinated gelatin suppositories are...
packaged in tightly closed glass containers to prevent moisture content.
Polar drugs generally move through membranes via...
paracellular transport or through channels
HEPA Filters flow in _______________ flow lines to lessen turbulence.
parallel
Because denaturation reactions are not strong enough to break ______________ bonds, the ______________ structure remains unchanged.
peptide; primary
Microencapsulation Drug Release happens during...
permeation through the membrane wall
Therapeutic Equivalents
pharmaceutical equivalents that produce the same effects in patients
Rapidly Dissolving Drugs empty during... and empty as a ___________.
phase 2-3; bolus
pKa is a ______________ property
physical
Physicochemical properties =
physicochemical barriers
Post-translational modifications (e.g., glycosylation, phosphorylation, proteolytic cleavage) sometimes needed for a protein to be...
physiologically active
Sebaceous glands empty into the follicles to form the...
pilosebaceous unit
Soft capsules are generally enveloped by a...
plastisizer (possibly spelled wrong)
Cocoa Butter *Substitutes* don't have the problems of _______________________ and/or _______________
polymorphism, rancidity
Y-Site
port on an IV line used for administering medications or alternate fluids that may or may not be compatible. *Flush w/ normal saline after each administration
Facility Design: Filtered & cooled airflow and maintain ______________ pressure
positive
Therapeutic antibodies are...
precisely targeted biopharmaceuticals that recognize and bind to a cell surface antigen and then trigger a biological response.
By what mechanism are most drugs given orally absorbed?
simple passive diffusion
"Eutectic mixtures have good...
skin absorption"
Describe the material within the large intestine?
slow and viscous
The longer it takes to reach the plateau value the _____________ the absorption rate; so we can say that something that plateaued faster was absorbed ______________.
slower; faster
glycerinated gelatin dissolves ____________.
slowly
Carriers are located in the...
small intestine
Tablet triturates or molded tablets are...
small masses of molded powders with rapidly soluble materials
Type II Glass
soda lime treated glass *Mainly for LVP's* treated = internal surface has been treated with carbon dioxide to dealkalyze the surface, making it less reactive.
Polymorphs: Differences (Melting Point, Density, Solubility) are only in...
solid/crystalline form
In general, the greater the degree of solvation, the lower the...
solubility dissolved in a medium that is the same as the solvate molecule
Also, ______________ > 100 ug/ml, _________ of < 500 Da, & _________ < 10 mg/day desired for a good candidate for passive transdermal delivery
solubility; size; dose
Permeability depends on... (2)
solute and membrane properties
The drug must be in ______________ to be ______________.
solution; absorbed
Alcohol USP (Ethyl alcohol; ethanol) is a widely used ______________.
solvent
Gravity Method
special IV bag with transfer leads attached
Production facilities for manufacture of parenterals:
special floor plan; filtered air supply; uv lights; sterile equipment & work clothing
Automated TPN Compounding requires ______________ ___________ from LVPs.
specific gravity
Polishing step may precede...
sterile filtration
Laminar-airflow work benches (LAFW), also known as ____________ ____________, are available for aseptic handling
sterile hoods
Parenterals must be...
sterile, pyrogen-free and of exceptional purity as this route circumvents the highly efficient protective barriers of the human body
Where are acids going to be more un-ionized?
stomach
Rheogram (F vs G, Flow curve) is a...
straight line passing through the origin
What emotional state(s) decrease emptying?
stress, anxiety, and depression
Natural & Synthetic Polymers
structural backbone for drug delivery systems
Sugar Coating: Most of the 50-100% weight increase occurs at the _________________ stage.
subcoating
Oily injections can be given _________________
subcutaneously
The Duros implant is most often implanted _____________________.
subcutaneously
Biopharmaceutical
substances produced in living systems by biotechnology and used for therapeutic or in vivo diagnostic purposes. These would include therapeutic proteins and peptides, antibodies, nucleic acid derivatives, DNA preparations.
Dissolving a water solvate (Hydrate) in water tends to...
suppress solubility
An emulsifying agent is a...
surfactant
Emulsifiers can act like ___________________ to reduce interfacial tension, or may act by forming a ________ between surfaces or for an electrically charged layer to keep phases ________________.
surfactants; film; separate
Barrel & plunger:
syringe tip may have locking or slip-tip connections
Drugs absorbed through transporter membranes should be...
taken with food
Steam Sterilization aka...
terminal sterilization
Rate of Shear (G) is directly proportional to...
the Shearing stress (F)
Unstirred water layer affects...
the absorption of the unionized form of the drug
Tablet weight and thickness is controlled by... (2)
the amount of die fill and compression pressure.
Parenteral Vehicles: Only __________________ oils should be used and must remain clear when...
vegetable; cooled to 10 deg C
Biosimilarity
the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components and there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.
Dry Powder Inhalers can deliver drug to...
the deep lungs
The fate of the active drug depends on...
the delivery system.
For Urinary Excretion Studies to be valid...
the drug must be excreted more than about 20-30%
The more pressure....
the finer the mist/particle
Interchangeable products may be substituted for the reference product without...
the intervention of the prescribing health care provider.
Antrum
the last part of the stomach before the pylorus, helps to prevent food from entering the intestine before it should. The major portion of digestion takes place in the antrum as food is held a long time before entering the duodenum in a very slow, methodical manner.
Eye drops are generally low capacity buffers because
the manufacturers want the solution to result in a pH to ~7.4, which is the average pH within the eye.
What does the concentration gradient tell us?
the net direction of molecules
Degree of Polymerization is determined by...
the number of monomers in a polymer chain.
Single Dose vs. Multiple Dose Containers/Vials are primarily different due to...
the possibility of preservatives in Multiple Dose Containers/Vials
Innovator
the product that went through the NDA process, usually the brand name.
Bioavailability
the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of drug action.
Polar compounds would not easily cross...
the relatively lipophilic membrane
Biopharmaceutics
the science that examines the interrelationship between the physical and chemical properties of a drug, the pathology and normal physiology of the patient, the dosage form in which the drug is given, and the route by which the dosage form is administered on the bioavailability.
Non-Newtonian: Plastic Flow: Plastic flow (Bingham body) does not begin to flow till...
the shearing stress exceeds the yield value
Aerosols: Particle size controls...
the site of action
The higher the calories, ...
the slower the emptying
Ions react by...
their equivalent weight
FDA may only get involved with a dietary supplement once...
they've identified an issue.
Carriers only respond...
to specific functional groups
Label must be _____________ and not ________________
truthful; misleading
Polymorph
two minerals that have the same chemical composition but a different crystal lattice structure, which may affect melting point or solubility
Method of analysis for Urinary Excretion Studies must measure only...
unchanged drug
Parenteral route of administration implies injection of the drug...
under or through one or more layers of skin or mucous membranes
A weak acid drug would be more __________________ at the low pH of the stomach.
unionized
Weak acids are ________________ in the stomach, while weak bases are ________________ in the stomach.
unionized; ionized
What happens when you overheat cocoa butter?
unstable α form
Trapezoidal Rule
use trapezoids to evaluate integrals (estimate area) of the AUC
Thermal Microporation
uses focused thermal energy to create hundreds of tiny channels in the surface of the skin
Glass tubes are _____________
vacuumed
Area =
½(a+b)•c
______ is cocoa butter's stable form
ß
Secondary Structure
α-helix
Physiologic Factors Affecting Rectal Suppository Absorption: (3)
•Colonic content •Circulation route •pH/buffer capacity
Physicochemical Factors Affecting Rectal Suppository Absorption: (3)
•Lipid-water solubility •Particle size •Nature of base
In the event that the pH is the same for stomach and small intestine, then the absorption rate may change due to...
∆ in surface area