Pharmaceutics I - Exam 2
What is dissolution?
the process of releasing drug molecules from dosage forms into solution -process of dissolving
delayed onset has a (longer/shorter) lag time
longer
A weak acid drug has a pKa of 4. What is the % ionization in the stomach when the patient is fasted (gastric = 2) compared to fed (gastric = 5)
% ionization = 1 / 1 + 10^pka - pH x 100 fasted = 0.99 % fed = 90 % patient should take without food for better absorption?
relative bioavailability equation - oral administration
(AUC) solid / (AUC) solution slide 79 and 80
Advantages to effervescent tablets
-carbonation masks unpleasant tastes -protects low sensitive material in stomach -assists in delivering large doses -no need to swallow tablets! -enhanced absorption of some active drugs compared to other formulations
What method is used to make ointments and suspensions?
levigation
Biological membranes
lipid layer attached on both sides to a protein layer
Do liquids or solids empty from the stomach faster?
liquids
The pH in the duodenum is slightly (higher/lower) than the ileum
lower - more acidic
Effervescent tablets (alka-seltzer) release CO2 when in contact with water due to which ingredients
-citric acid -tartaric acid -sodium bicarbonate
Advantages of using capsules as a dosage form?
-deliver powders, granules, beads, prefabricated solids, semisolids, and liquids (that dont dissolve in gelatin) -mask the taste/odor of a drug -relatively easy to swallow and can be administered with food -Bioavailability of a drug is BETTER than compressed tablets -easy to formulate (no need for granulation) -can be administered orally, rectally, vaginally
What types of excipients are used in tablets?
-diluents -binders/adhesives -disintegrants -lubricants, glidants -colorants, flavorants -coatings
Size distribution of powders affect...
-dissolution rate -absorption -stability -texture and taste -flow and sedimentation rates
What are some benefits of using a powdered dosage form?
-doses can be individually prepared = easy for children and elderly who have difficulty swallowing -RAPID ONSET - bc powder doesn't have to disintegrate, absorption dependent on dissolution only -generally more stable than liquid dosage forms
Benefit and disadvantage to mixing powders in water for oral distribution?
-faster absorption -undesirable taste of oral powders
What are some reasons why food may affect absorption of drugs?
-food can delay gastric emptying -food can change the pH of the stomach -food stimulates bile flow -food increases splanchnic blood flow -food can change the luminal metabolism of the drug -food can interact with the drug physically and chemically
What are 2 reasons why absorption is favored in the small intestines?
-length -surface area -(blood flow) -(thin epithelium)
Problem with counterfeit drugs
-may not include active ingredient -may contain too little or too much active ingredient -may contain the wrong active ingredient -may be in fake package
How can we minimize eutectics
-mix material with bulky absorbent powder -mix with spatula rather than mortar and pestle to avoid compression
How do you evaluate the in-vivo performance of an orally administered drug?
-pK profile of orally admin drug -onset (lag time and tmax) -Cmax -AUC (area under the curve) / systemic exposure -bioavailability
What types of factors affect dissolution?
-particle size -solubility and hygroscopicity -type and conc of disintegrant, binder, and lubricant -compression of granulation or tablet
What types of substances can be used to fill capsules?
-powder or granules -pellet mixture -paste -capsule -tablet
Why are some tablets sugarcoated
-quickly dissolves after swallowing bc water soluble -provides a barrier to unpleasant taste/odor -enhances appearance and taste disadvantage - may add 50% to weight and bulk must be imprinted
Disadvantages of capsules
-sensitive to relative humidity -not suitable for liquids that dissolve gelatin not suitable for highly soluble salts (KCl, NH4Cl) bc sudden release of these compounds in the stomach can cause stomach irritation -not suitable for pediatric patients -capsule filling process is slower than tablets -not suitable for efflorescent or deliquescent material - soften or produce bitterness
How to minimize efflorescent problem
-use anhydrous from of drug -use bulky drying powder -avoid compacting method of mixing
what is the range of very slightly soluble?
0.1 - 1 mg/mL
Steps using the rule of 7s
1. convert weight of powder to grains 2. subtract from 7 3. match size to rule of 7s list
what is the range of slightly soluble
1 - 10 mg/mL
A good effervescent blend consists of both citric and tartaric acid in what type of ratio
1 : 2 ratio
1 grain = ? g 1000 mg (1g) = ? grains
1 grain = 0.0648 g 1000 mg = 15.43 grains
To increase gastric emptying time - when should the patient take their drug?
1 hour before meals OR wait 2-3 hours after consuming a heavy fatty meal
What is the range of particle sizes from fine to coarse
1 um - 1 cm
Friability test: max weight loss of no more than _________ is generally acceptable
1% (hardness and friability - tendency to break into smaller pieces)
What particle size can reach the lungs?
1-5 um
Food effect s more pronounced when the drug is taken which 3 ways?
1. 20 mins before a meal 2. with a meal 3. 2 hrs after a meal
What physiological factors affect oral absorption?
1. Dissolution 2. pH effect 3. Solubility on GI tract 4. Drug Transport
How are effervescent tablets prepared?
1. Dry/fusion method 2. Wet method
Name 2 characteristics of effervescent tablets (Alka Seltzer)
1. Fast disintegration 2. Release CO2
What are the steps in preparing a powder formulation?
1. Obtain raw materials 2. analyze materials - particle characterization
How do drugs cross the mucous membrane of the epithelial cells in the GI tract?
1. Paracellular transport - between cells 2. Passive diffusion - through cells 3. carrier-mediated transport - facilitated 4. Efflux - flowing out of the cell
What 3 main factors affect oral rug absorption?
1. Physiochemical factors 2. Physiochemical properties - anatomic features -food factors -disease states and drugs 3. Dosage form factors
How can we minimized segregation when mixing/blending particles?
1. Select excipients with DENSITY similar to API 2. Granulation of powder 3. selection of narrow size fraction range
What tools can be used to blend powders?
1. V - blender 2. Ribbon blender 3. Fluidized bed mixer
What formulations strategies improve absorption for BCS II drugs?
1. addition of surfactants 2. reduction of particle size 3. suitable polymorphs or amorphous materials
Addition medicated powders from routes other than oral admin
1. aerosol powders - blowing or inhaling into body cavity 2. dry powder inhalers (DPI) - lungs 3. topical powders - skin Granules
What factors may influence powder blending?
1. amount of ingredients 2. density 3. surface area 4. particle size and shape 5. particle charges 6. powder flow
What should you do if the particles of all the ingredients are different in size?
1. change the excipient/material grades 2. Perform dry/wet granulation
What are the health risks of counterfeit drugs?
1. counterfeit drugs may not contain the active ingredient = no therapeutic effect to the patient 2. improper dosages of correct ingredients or hazardous ingredients = unexpected side effects, allergic reactions, worsening medical condition
components of film coated tablets
1. film forming polymers 2. plasticizers 3. colorants 4. binder/ filter
What are the 6 different powder blending techniques?
1. geometric dilution 2. spatulation 3. trituration 4. V-blender 5. Ribbon blender 6. Fluidized bed mixer
What types of drugs are offered as powders for oral administration?
1. laxatives 2. analgesics 3. antibiotics
What are 2 ways you can slow down or control drug release disintegrating?
1. minimal/delayed increase in SA = erosion 2. thickening the diffusion barrier by increasing h = swelling
What strategies can be used to increase dissolution?
1. reduce particle size (to increase SA!) 2. increase dissolution rate constant k by -increasing cs with increased temp -reducing the viscosity
How do drugs overcome barriers/biological membranes?
1. simple diffusion 2. facilitated diffusion (3. active diffusion)
Name 2 characteristics of orally disintegrating tablets (ODT)
1. they disintegrate in the mouth without chewing 2. good for pediatric or geriatric patients
Event/barrier sequences for oral administration
1. transverse GI membranes 2. gain entrance into general circulation 3. pass to organ or tissue it has affinity with 4. gain entrance to that tissue 5. enter its individual cells
How does the USP define particle size?
1. very coarse No 8 2. coarse No 20 3. moderately coarse No 40 4. fine No 60 5. very fine No 80 -determined by the percentage of particles that pass through standard sieves of varying fineness while being mechanically shaken
What factors MUST be controlled for tablets
1. weight 2. weight variation 3. content uniformity 4. thickness 5. hardness 6. friability 7. disintegration time 8. dissolution profile
What is the range of sparingly soluble
10 - 33 mg/mL
range of granules sometimes used in tablets
12 - 20 mm
hard gelatin capsules normally have a moisture content of _________%
13-16%
What bloom strength is suitable for capsules?
150 - 180 g
How many pieces are shells composed of? What are the pieces called?
2 pieces - a body and a cap
Excellent repose angle
25-30
What is the repose angle of powders with excellent flow? Poor flow?
25-30 46 -55
particle sizes range from _________ - _________ to flow freely if shape is amenable
250 - 2,000 mm
freeze dried tablets dissolve in the mouth in __________
3 seconds
Stomach emptying time for liquid - small meal?
30 mins
oral disintegrating tablets (ODT) dissolve in the mouth in _____________
30 seconds
True or False: Disease states do not affect gastric emptying time
False
a physician prescribes 30 capsules each containing 300 mg of ibuprofen for a patient. The pharmacist only have 400 mg tablets on hand - how many tablets would be needed to obtain the correct amount of ibuprofen prescribed by the doctor?
30 x 300 = 9,000 mg 9,000 / 400 = 22.5 tablets
Good repose angle
31 - 35
What is the range of soluble in mg/mL
33-100 mg/mL
Fair repose angle
36 - 40
typical range of granule size
4 - 12 mm
A pharmacist needs to prepare 50 capsules each containing 4 mg of estriol and 1 mg of estradiol. A size 3 capsule is selected for use. Capsules are filled individually with the following Estriol = 250 mg Estradiol = 190 mg Lactose = 320 mg How many mg of each component are needed in total?
4 x 50 = 1 x 50 =
passable repose angle
40 - 45
poor repose angle
46 - 55
very poor repose angle
56 - 65
the active ingredient in each dosage form must range between 85 -115% with a SD of _______ %
6 %
very very poor repose angle
66 and higher
Stomach emptying time for a solid meal?
70 - 130 mins
Stomach emptying time for liquid - fasted state?
8-15 mins
Gastric pH fasted vs. fed
Fasted = 1.4 - 2.1 Fed = 4.3 - 5.4
What are the % ionization equations from acids and bases?
Acids: % ionization = 1 / 1 + 10^pka - pH x 100 Bases: % ionization = 1 / 1 + 10^pH - pka x 100
What is a granule?
An AGGLOMERATE of powdered materials. (They are made from powders, we get powders and agglomerate them and get bigger particle size to get granules)
Drugs that decrease acid secretion in stomach
Anticholinergic drugs (atropine) Proton pump inhibitors (omeprazole) H2 receptor blockers (formatidine) Antacids
Bulkiness equation
B = 1 / Pa
Formulation strategies are important for which drugs according to the BCS?
BCS Class II
Bioequivalenet drug products vs. therapeutic equivalents
Bioequivalent = pharmaceutical alternatives whose rate and extent of absorption do not show significant differences therapeutic = pharmaceutical equivalents that provide essentially the same therapeutic effect when administered to individuals using the same dosage regimen
What are the differences between hard and soft shell capsules?
Capsules made of 2 pieces - body and cap - are referred to as HARD shell capsules One-piece capsules are referred to as SOFT shell capsules
Biopharmaceutical classification system (BCS) Class I Class II Class III Class IV
Class I = high solubility, high permeability Class II = low solubility, high permeability Class III = high solubility, low permeability Class IV = low solubility, low permeability
Most drugs fall into which class?
Class II = low solubility, high permeability
Conc gradient equation
Cright - Cleft / xright - xleft = deltaC/deltaX x = position
A selected powder has a true density (p) of 3.5 g / cc. Experimentally, 2.5 grams of the powder measures 40 mL in a cylindrical graduate. Calculate true volume, void, porosity, apparent density, and bulkiness.
D = m / v ---> 3.5 g / cc = 2.5 / v true volume = 0.714 cc void = V bulk - V / V bulk ---> 40 - 0.715 / 40 void = 0.982 Porosity = void x 100 = 0.982 x 100 = 98.2% Apparent density = mass / bulk volume ---> 2.5 / 40 apparent density = 0.0625 g/mL Bulkiness = 1 / Pa ---> 1 / 0.0625 = 12 mL / g
What is an example of dry powder dosage forms?
DPI - Dry Powder Inhaler
Bioavailability equation for IV
F = 1 - E F = bioavailable E = hepatic extraction ratio
Bioavailability equation for other routes of administration besides IV?
F overall = (1 - E)F absorbed
Where can a pharmacist look up to see which drugs are experiencing a shortage?
FDA drug shortage website and the ASHP drug shortage website
What is the difference between the FDA drug shortage website and the ASHP (american society heath-system pharmacists) drug shortage webpage?
FDA is available for the public and the ASHP is only available for healthcare professionals ASHP also lists more shortages than FDA
What happens when a drug isn't available?
Find a pharmaceutical equivalent or a pharmaceutical alternative
Flux equation and units
Flow rate (mol s-1) / area mol m-2 s-1 or mol/s/m2
What disease states increase stomach emptying time?
HIV-AIDS celiac disease (same as increasing intestinal motility)
What disease states increase intestinal motility?
HIV-AIDS (diarrhea) Celiac disease
USP dissolution apparatus I and II
I - tablet is placed in the basket II - tablet is placed at the bottom under the paddle
In-vivo vs. In-vitro
In-vivo (in living organisms) 1. PK studies 2. PD studies 3. Bioavailability (BA) 4. Bioequivalence (BE) In-vitro (outside of living organisms) -Dissolution rate -Drug release rate -Permeation studies -Pre-formulation studies
Which comes first? - In-vitro or In-vivo?
In-vivo comes first! - studies occurring in living organisms = PK, PD, BA,BE
Medications may increase, decrease, or delay absorption of drugs. Give examples of each.
Increase: -Propanolol & metoprolol -Vitamin A derivatives -Riboflavin Decrease: -Warfarin -Penicillins -Erythromycin Delay: -Valproate -some NSAIDs (diclofenac) -aspirin
Which disease states changes the permeability of the gut wall and GI flora?
Inflammatory bowel disease (Crohn's)
What is sieving?
the process of particles passing a series of sieves/screens by mechanically shaking
What are the different types of bloom categories?
Low bloom medium bloom high bloom
What is MedWatch? What do they do?
MedWatch is the FDAs product safety reporting program for heath professionals, patients, and consumers MedWatch receives reports from the public and publishes safety alerts for FDA-regulated products
US NIST
National institute of standards and technology
Dissolution as a function of time correlates to which equation
Noyes-Whitney Equation
The rate of dissolution is described by which equation?
Noyes-Whitney Equation dc / dt = kA (cs - ct) or dc / dt = D / h A(cs - cb) when K = D / h
Pharmacokinetics vs. Pharmacodynamics
PK = "what the body does to the drug" - the study of the time course of drug movement (kinetics) in the body during ADME PD - "what the drug does to the body" - the study of the relation of the drug conc at the site of action (receptor) and its therapeutic response as a function of time
What disease states slow intestinal motility?
Parkinson's disease Depression CHF (congestive heart failure)
How is tapped density measured?
by tapping on a graduated cylinder containing a sample until little to no volume change/reduction is seen
Porosity equation
Porosity (%) = void x 100% OR V bulk - V / V bulk x 100
Trituration
Small scale = the process of reducing particle size by grinding with a mortar and pestle Large scale = particle size is reduces by using a jet-Mills / Mechanical- Mills and pulverizers
List the smallest to largest size capsules
Smallest: 5 4 3 2 1 0 00 000 Largest:
Dry granulation method
Specifically designed for preparations that cannot be wetted (degrade in the presence of moisture or high heat) 1. roll compaction 2. slugging
What machine is used to reduce particle size?
Spiral Jet-mill
Method used for Particle Size Analysis
The Sieving Method - USP
Who set the standard and were to find the standard of measurement?
The US NIST (national institute of standards and technology)
Gelatin shells can be a)hard b)soft C)both
c - both hard and soft
What order of kinetics correlates to liquids and solids? a) first order b) second order c) zero order
liquids = first order (bc faster) solids = zero order (bc constant)
Acid liable drugs require what type of coating?
enteric coating
What is bloom strength?
a measure of the strength a stiffness of the gelatin
What is a gelatin?
a protein obtained by partial hydrolysis of collagen (protein from collagen) - derived from skin, connective tissue, and bones of animals
What is a capsule?
a solid dosage form in which the drug is enclosed a hard or soft container or shell.
What is a powder?
a solid substance composed of finely divided particles - powders are dosage forms of a solid or mixture of solids
What is the grey market?
a supply channel that is unofficial, unauthorized, or unintended by the original manufacturer
Which type of coating has delayed release features?
enteric coatings - designed to protect tablet in gastric acid and deliver to the intestines
Angle of repose is used to
estimate the flow properties of a powder
True or False: Most drugs must pass more than one of these membranes types before it reaches its site of action
True
True or False: What you eat will change the GI emptying time
True
powders become sticky or even liquify when mixed together
eutectics
Type A vs Type B gelatin
Type A = skin gelatin Type B = bone gelatin
What does USP stand for?
United States Pharmacopeia
What does the US NIST stand for?
United States national institute of standards and technology
Void equation
V bulk - V / V bulk
Particle Size: No 8
Very coarse
How are granules prepared?
Wet granulation and dry granulation methods
Besides oral administration, how else might tablets be administered to patient?
buccally sublingually vaginally
Food in the GI tract may affect the _______________ of drugs
absorption
What disease states increase gastric pH?
achlorhydria HIV-AIDS (achlorhydria) Aging
What happens if the active drug powder is too little to fit into a capsule?
add diluent to increase size of capsule
when making a powder formulation, particle size of ingredients should be... a) different b) larger c) similar d) larger
all ingredients should be similar in size!
are crystalline or amorphous drug forms more soluble?
amorphous
no definite structure, not ordered, metastable
amorphous
the (anhydrous/hydrated) form is usually more soluble than the (anhydrous/hydrated)
anhydrous = more soluble than hydrated
What disease state increases gastric emptying rate?
anxiety
Pa
apparent bulk density
If a company wanted to make a non-disintegrating dosage form what type would they make? a) tablet b) erosion c) swelling d) powder
b - erosion
how would you decrease viscosity of a solvent?
by drinking water
How is sedimentation rate determined?
by measuring the particle settling viscosity in a liquid medium via stokes law
What disease states decrease stomach emptying time?
long standing diabetes
Administered drug must overcome ____________ to arrive to the site of action in effective concentrations
barriers -biological membranes
spherical powders flow ___________ than needle shaped powders
better
Angle of repose: SMALLER the angle means
better flow!
_________________ is a measure of the amount of drug that can reach systemic circulation
bioavailability
What is the full name of BCS for drug classification?
biopharmaceutical classification system
the noyes whitney equation (can/cannot) describe the condition when the drug particle first encounters the solvent when the particle is completely dissolved into the solvent
cannot - only in between
Bioavailability is better in ___________ rather than ___________
capsules, tablets
__________ empty faster than ____________ which empty faster than ___________
carbs, protein, fats
What are some examples of colorants
change color -azo -xanthene dyes -iron oxide pigments
Particle Size: No 20
coarse
Tablets are prepared primarily by ______________
compression
What disease states reduce intestinal blood flow?
congestive heart failure (CHF)
What should you do if you believe a patient has received a counterfeit drug?
contact the FDA immediately via MedWatch - to report the fake drug
definite identifiable shape, ordered, low energy state
crystalline
some combinations of powders react when mixed - commonly ______________ and _____________ agents
explosive mixtures - oxidizing and reducing agents
What do the variables in the Noyes-Whitney equation mean? dc/dt = kA (cs-ct)
dc/dt = dissolution rate (kg/s) k = dissolution rate constant (also written D / h) A = surface area Cs = saturated diffusion layer Ct = concentration of the drug in bulk solution (also written as Cb)
What is this equation solving for? What does each variable mean? dc/dt = DA/h (cs - cb)
dc/dt = rate of dissolution D = diffusion coefficient A = surface area (of the barrier) h = thickness (of the stagnant layer/diffusion layer) cs = saturation conc of drug in diffusion layer cb = conc of drug in bulk of solution
How would you decrease dissolution? dc/dt = kA (cs-ct)
decrease dissolution constant (D/h), decrease A, and decrease concentration gradient
How might you increase the dissolution rate?
decrease particle size and decrease viscosity
When may polymorphs be formed?
dependent on conditions of crystallization - temperature, solvent, and time
What disease states decrease gastric emptying rate?
diabetes and migraines
Noyes-Whitney equation determines the rate of ________________
dissolution
If the dissolution of a drug particle is slow - the absorption rate is dependent on what?
dissolution itself is the rate limiting step
counseling points for effervescent tablets
dissolve in water - do not swallow
What is a drug delivery system?
drug formulation and the interactions among the drug, its formulation matrix, its container, and the patient
What is a counterfeit drug?
drugs sold under a product name without prior authorization
Granules are defined as
dry aggregates of powder particles - typically 4 - 12 mm
What is the best dosage form for lung delivery?
dry powder inhalers (DPI)
What are the sections of the small intestine? Length, Diameter, and pH
duodenum, jejunum, ileum length = 6.25 m diameter = 4-5 cm pH = 6-8
Bile acids are secreted into the ___________ and reabsorbed in the ____________
duodenum; ileum
crystalline powder that contains water of hydration or crystallization, may become sticky, pasty, or liquify
efflorescent powders
Powders mixed in water are ideal in which populations?
elderly and pediatrics due to difficulty swallowing
True or False: There are no tablets that can be 3D printed
false - spritam
What types of food dramatically inhibit emptying of stomach?
fatty acids (fats), carbs, and amino acids high energy meals = decreased emptying
What is the "punch method" used for?
filling capsules -an extra 2 doses or 10% whichever is greater must be added to account for loss
Particle Size: No 60
fine
The rate in which particles flow through an area is called
flux
Levigation
forming a paste with a liquid (levigating agent) that the powder is insoluble - used when preparing ointments and suspensions
Capsule shells are usually made of what type of material?
gelatin
Hard gelatin capsules are made of ______________, ________________, and ______________
gelatin, sugar, and water
smallest quantity of AI is mixed with equal amount of diluent, repeated until all material is mixed
geometric dilution
particle smaller than 100 mm -
have a problem with flow
What does E represent?
hepatic extraction ratio (E)
Bioavailability is dependent on the ______________
hepatic extraction ratio - the fractions of absorbed drug (Fabs)
Diffusion flux goes from __________ to __________ conc
high to low
Blending powders in important for obtaining a _________________ mixture
homogenous
HLB
hydrophilic-lipophilic balance
Vegetarian capsules do not contain animal by-products...so what are they made of?
hydroxypropyl methylcellulose (HPMC), starch, and carrageenan
____________ powders absorb moisture from the air while ___________ powders absorb moisture from the air and partially/completely liquify
hygroscopic; deliquescent
lipid based systems and solid lipid nanoparticles (improve/don't improve) drug absorption
improve
IVIVC
in vitro, in vivo correlation
dc/dt = kA (cs-ct) or dc/dt = D/h A (cs-ct) what happens when you increase K? what happens when A is decreased? what happens when h is increased what happens D is increased? What happens when conc gradient is increased?
increased k = faster dissolution rate decreased a = slower dissolution rate increased h = slower dissolution rate increased d = faster dissolution rate increased conc gradient = faster ≥
How does erosion effect the equation dc/dt = (D/h) A (cs-cb) ?
increases A (surface area)
Drugs administered by _______________ injection are introduced directly into the circulatory system
intravenous
Name a benefit of intravenous administration?
intravenous administration avoid absorption
The (ionized/unionized) form of a drug is more soluble
ionized
Particle size and shape in a powder is _________
irregular
Can you split a extended/delayed release tablet for patients?
it depends if the extended release features are coming from the coating - if so then no because when you split the tablet the center wont be coated
If the dissolution of a drug particle is rapid - the absorption rate is dependent on what?
its ability to pass the membrane barrier
diluent
lactose, microsrystalline cellulose, starch, dicalcium phosphate
Do fine or large particles flow more freely?
large
generally capsules can hold (more/less) than 1 gram of material
less
ionized form is (more/less) lipophilic than the nonionized form
less
What is the range of practically insoluble in mg/mL
less than 0.1 mg/mL
advantages of granules vs. disadvantages
lower surface area - better for flow enhancement more stable to atmospheric problems minimizes powder segregation less likely to cake more easily wetted more time a labor required to prepare
what might you want to add to a eutectic mixture?
magnesium carbonate, kaolin, or light magnesium oxide (diluent or absorbant)
Geletin coated tablets do what to the surface? Another name? Advantages
make the surface smoother more tamper evident Gel-caps
What are some examples of opacifiers
makes clear gelatin opaque - protects contents from light -titanium dioxide
What are some examples of flavorings
mask the taste of the drugs -ethyl vanillin -essential oils -sucrose
particle size within 75 - 250
may be a problem or may flow freely
What type of meal is most likely to affect GI physiology?
meals high in calories and fat
Drugs that increase GI mobility
metochlopramide Cisapride
What levigating agents are commonly used during the levigation process of making ointments and suspensions?
mineral oil and glycerin
Eutectic mixtures
mixture of two or more substances that may liquefy when intimately mixed
Particle Size: No 40
moderately coarse
Effervescent granules must be protected from what in their packaging
moisture
simple diffusion
molecules pass cell membrane driven by a conc gradient (high to low)
Active transport
molecules pass membrane by moving from low to high concentrations assisted by transmembrane carriers - USES E
Facilitated diffusion
molecules pass membrane from high to low conc using transmembrane carriers
The pH of the stomach when fed is more (basic/acid) compared to the pH of the stomach when fasted
more basic
film coated tablets are better than sugarcoated bc
more durable, less bulky, and less time consuming to apply
multiple compressed method is used to make which types of tablets
multiple layered tablets or tablet within a tablet = multiple compression
What is Flux?
net rate at which particles move through a certain area - net movement of particles across and specified area in a specified period of time = flow rate / area ex) cars through pay toll, molecules through cell membrane
What does acid liable mean?
not stable in acid/ degraded in acid
Reducing the particle size increases ___________ and ____________
number of particles; total surface area
What type of tablet is best for elderly and children?
orally disintegrating tablets (ODT)
The unit of matter having a defined physical dimensions
particle
If smaller particles go deeper in the lungs, why don't we use the smallest particles possible for inhalers?
particles that are too small wont stay in the lungs - they will simply be exhaled out which will not provide the appropriate therapeutic effects to the patient
Which diffusion type describes Fick's First law of Diffusion?
passive diffusion - driven by high to low conc
pharmaceutical equivalent vs. pharmaceutical alternative
pharmaceutical equivalent = drug product that contains identical amounts of active drug ingredient (same salt or ester) in identical dosage forms pharmaceutical alternative = contain identical therapeutic moiety but not necessarily in the same amount or dosage form (as the same salt or ester)
What are some examples of plasticizers
plasticizers reduce rigidity of gelatin and make it more pliable -glycerol -sorbitol -propylene glycol
The ability of a solid to exist in more than one from or crystal structure is
polymorphism
a substance that exists in more than one crystalline form
polymorphism
Angle of repose: LARGER the angle means
poor flow
_______________ is used to make powders and capsules
powder
What happens if the particles are not uniform in shape - porosity is low
powder cant be properly mixed
Wet granulation method
powder is moistened with water or other liquid 1. oven dry method 2. fluidized bed processing 3. high shear granulation
Classification of the USP solubility in order
practically insoluble = less than 0.1 very slightly soluble = 0.1 - 1 slightly soluble = 1 - 10 sparingly soluble = 10 - 33 soluble = 33 - 100
pre-compression vs main compression rollers
pre-compression = removes air main compression rollers = full force compression
disintegrants
pregelatinized starch, croscarmellose, sodium starch glycolate
What are some examples of preservatives
prevent bacterial and fungal growth/ microbial growth -methylparaben -propylparaben
the shape and dimensions of tablets are determined by the use of various shaped __________ and __________
punches and dies
absolute bioavailability equation - IV administration
ratio of AUC and dose (AUC / D) po / (AUC / D) iv slide 79 and 80
Comminution is the process of
reducing particle size
What should you do if the packaging or labeling of a drug looks irregular? (counterfeit drug)
report to the FDA and manufacturer immediately
The rule of 6s and 7s are used to determine what?
rules for selecting capsule size
What happens to sedimentation rate as viscosity increases?
sedimentation rate increases
What is a potential issue when mixing/blending powders?
segregation can occur due to particle size variation -->recall brazil nut effect - large molecules tend to sit on top hygroscopic and deliquescent powders efflorescent powders eutectics explosive mistures incorporating liquids
Immediate release (IR) disintegrate in a (long/short) period of time - less than how many minutes
short period of time - less than 30 mins
Particle ________ and ___________ can be determined by the % of powder that passes through the standardized sieves while being mechanically shaken (sieving)
size and distribution
______ is composed of several layers of cells while the ________ is made up of a single layer of cells, and the _________ is made of less that one cell thick
skin; intestinal epithelium; membrane of a cell
Calculating average particle size
slide 22 (N)(D) OR ND / sum of numbers
______________ particle sizes are more soluble
smaller
Why do you need lubricant in tablets?
so that they dont stick to the punches
Polymorphs only exist in the _________________ state and never in _____________
solid state, never in solution
Dissolution is dependent on _______________ and ________________
solubility and surface area
Salt forms are generally more __________, but have lower permeability
soluble
Put in order of fasted disintegration and gastric emptying time to the slowest capsules, suspensions, tablets, solution
solution, suspension, capsules, tablets
combining and mixing substances by means of a spatula
spatulation
What happens if the active drug powder is too large to fit in a capsule?
split it into 2 and used 2 capsules /day
Tablet that are scored or grooved allow for patients to
split the tablet - to swallow smaller portions
Noyes-Whitney equation is only applicable under what type of conditions?
steady state
What is the pH of the stomach, duodenum, and ileum?
stomach: 1-4 ~2 duodenum: 5-7 ileum: 7-8
Which has a faster absorption/dissolution - buccal or sublingual
sublingual
Why is it not good to increase SA too much?
surface tension may prevent solent penetration - therefore fine particles will float on solvent
non-disintegrating tablet vs sustained release
sustained release = swelling non-disintegrating = erosion
large capsules may be hard to _____________ while smaller capsules may be hard to ____________
swallow handle
What does swelling do to the dc/dt = (D/h) A (cs-cb) equation
swelling increased h
capsules may be filled with mini ____________
tablets
Why might some tablets not be able to be split
tablets that have a special coating and/or drug release feature might be compromised by slitting the drug
What does steady state conditions mean?
the concentration at the surface of the particle is NOT time dependent
What is a drug product?
the finished dosage form that contains the active and inactive ingredients (excipients) that make up the vehicle or formulation matrix
Bioavailability definition
the percentage of the administered dose that reaches systemic circulation after passing through the liver
Porosity
the ratio of volume of interspaces to the volume of mass % of empty space porosity % = percentage of empty space
Micrometric definiton
the science of small particles
Biopharmaceutics
the study of the relation of the physical and chemical properties of a drug to its.... bioavailability pharmacokinetics pharmacodynamics toxicologic effects
What is dissolution rate?
the time it takes for the drug to dissolve, especially at the absorption site
molded tablets are not as common today because
they are manually prepared
What does moisture active adherent (mucoadhesive) often used for
to prolong contact time of action at the mucous membrane
Drugs that reduce GI mobility
tricyclic antidepressant and antipsychotics (phenothiazines) anticholinergic (propantheline bromide)
grinding or pulverizing powders to create fine particles
trituration
True or False: Patients who take inequivalent drug products may experience therapeutic failures
true
True or False: polymorphs may possess different physiochemical properties such as stability, solubility, rate of dissolution, rate of absorption, and melting points
true
True density vs. apparent/bulk density
true = density of the material ONLY (doesnt include proe and void volumes) - determined by helium pycnometry apparent/bulk density = density of the material including pore and void volumes
True or False: freeze drying is another way that tablets may be formed
true!
Which gelatin has plasticity and clarity? Which gelatin has firmness?
type A - skin type B - bone
How can we estimate the flow properties of a powder?
use the angle of repose technique
How to minimize hygroscopic and deliquescent
use tight containers with desiccant packs or formulate with an inert drying powder
Particle Size: No 80
very fine
What are some examples of a solvent
water
Why do we have to analyze particle size, distribution, and angle of repose?
we need to understand and characterize the particles before making an appropriate formulation
What test does the USP perform to determine the uniformity of uncoated tablets?
weigh 10 tablets individually and calculate the average size
apparent/bulk density
weight of sample (mass) / bulk volume
true density equation
weight of sample (mass) / volume
How can you determine the volume that can fit in a capsule? What units are used for volume of a capsule?
when given density ---> D = m / v ..... solve for V mL for units!
When does duration of action occur for a drug (graphically)?
when the concentration is greater than the MEC (minimum effective concentration)
How would you graphically represent bioavailability? What would the x and y axis be labeled?
x axis = time y axis = plasma concentration Cmax = max concentration Tmax = time to max conc MEC = min effective conc MTC = maximum toxic conc
Do the shape a size play a role in flowability of powders
yes
Does the dosage form play a role in gastric emptying time along with food?
yes! -Least effect = solution formulations -Less effect = suspension, powders, 1-2mm particles -Greatest effect = tablets with long disintegration time, enteric coated tablets, and non-disintegrating tablets (sustained release)
