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)