Lecture 1: Innovations

Question 1

Vaccine innovations: types of vaccines

Answer 1

-mRNA vaccine
-vector vaccine
-protein subunit vaccine
-whole killed vaccine

Question 2

ADHD drugs

Answer 2

-methylphenidate
-amphetamine
-intuniv (nonstimulant)

Question 2

Methylphenidate drugs

Answer 2

-ritalin and concerta
-Daytrana patch

Question 3

Dissolution Testing

Answer 3

-method for insuring quality of tablets and capsules
-only method that can be lonked to blood levels and bioavailability

Question 4

5 Methods for insuring quality of tablers and capsules

Answer 4

1. dissolution testing
2. Assay
3. impurities
4. content uniformity
5. water

Question 5

disintegration vs Dissolution

Answer 5

1. Disintegrate FIRST
2. then DISSOLVE

Question 6

Tablet must first ehat before the drug caan dissolve?

Answer 6

disintegrate

Question 7

Dissolution from dosage forms

Answer 7

-dissolution of drug in GI fluid needed before absorption can occur

Question 8

DIssolution of drugs with high solubility

Answer 8

-few formulation problems

Question 9

Dissolution of drugs with low solubility

Answer 9

-absorption rate may be governed by dissolution rate
-if dissolution too slow = absorption bad

Question 10

Dissolution experiment

Answer 10

-place tablet in apparatus
-measure rate of dissolution

Question 11

dissolution tests measure

Answer 11

rate of release of drug from tablet

Question 12

Poorly soluble drugs can dissolve under:

Answer 12

-physiological conditions if its dose is sufficiently SMALL

Question 13

dose solubility volume

Answer 13

-may be more relevant than solubility alone
-even poorly soluble drugs can completely dissolve if the dose is small enough

Question 14

High solubilty definition

Answer 14

-largest human dose is soluble in 250mL or less of water throughout the physiological range of 1-8 at 37C

Question 15

Low solubility drug definition

Answer 15

-more than 250 mL of water needed to dissolve the largest dose
-any pH at 37C

Question 16

Why 250mL?

Answer 16

-estimated minimum gastric volume available
-based on volume of water recommended for ingestion during administration

Question 17

Bioavailability depends on:

Answer 17

-having drug in solution
-drug permeabilty

Question 18

Jejunal permeability

Answer 18

-high

Question 19

permeability determined by:

Answer 19

-90% or more of drug absorbed

Question 20

Least rigorous dissolution test for drugs with:

Answer 20

-HIGH solubility
-HIGH permeability

Question 21

Rigorous dissolution testing is needed for drugs with:

Answer 21

-HIGH solubility
-LOW permeability

Question 22

the most rigorous testing is needed for drugs with:

Answer 22

-LOW solubility
-HIGH permeability

-theses are BCS class 2 drugs

Question 23

BCS class 2 drugs

Answer 23

-LOW solubility
-HIGH permeability

Question 24

Methylphenidate

Answer 24

-LOW solubility
-HIGH permeability
-BCS class 2
-controlled release into blood stream

Question 25

Methylphenidate USP

Answer 25

-immediate release
-dissolution test:
-medium: water, 900mL
-requires >75% dissolved in 45 min

Question 26

Methylphenidate SR

Answer 26

-sustained release
-utilize polymers
-matrix and coated beads

Question 27

Metadate CD

Answer 27

-extended release beads
-medium: water

Question 28

extended release beads

Answer 28

-beads have varying coatings
-some immediate release and some extended release

Question 29

Methylphenidate vs metadate dissolution rate

Answer 29

-methyl plataues and requires another dose
-metadate keeps increasing

Question 30

Film Coating steps

Answer 30

-spray tablet with solution, solvent, plasticizer
-solutions wets surface and spreads
-solvent evaporates
-polymers entangle
-film forms by coalescence
-adhesion between coat and surface

Question 31

coating pans

Answer 31

-accelacota
-grover
-vector

Question 32

Fluid Bed coating

Answer 32

-blows hot air to circulate solvent particles to coat tablet

Question 33

Coating Process

Answer 33

-equipment
-parameters (nozzles)
-facility and ancillary equipment
-automation

Question 34

Nozzles

Answer 34

-liquid feed
-sometimes with air on either side

Question 35

Polymers for film coating: NONENTERIC

Answer 35

-HPMC
-Methyl hydroxyethylcellulose
-Ethylcellulose
-HPC

Question 36

ENTERIC polymers for coating

Answer 36

-release drug in small intestine
-acrylate polymers
-CAP
-HPMCP
-PVAP

Question 37

Matrix tab;et

Answer 37

-drug embedded in polymer matrix
-release by EROSION or DIFFUSION

Question 38

Elementary Osmotic Pump (EOP) in CONCERTA (OROS)

Answer 38

-semipermeable membrane
-CONTROLLED RELEASE
-keeps plasma levels stable
-water enters drug and creates pressure and pushes drug out into blood stream
-delivery oriface
-single or double chamber

Question 39

Single chamber oros

Answer 39

-water comes in and pushes drug MOLECULES out

Question 40

Double chamber Oros

Answer 40

-water comes in, fills, then pushes out drug SUSPENSION

Question 41

Dissolution rates of methylphenidate vs oros

Answer 41

-oros increases rapidly until leveling off at 100
-equals 3 doses of methyl

Question 42

Dissolution vs blood levels

Answer 42

-dissolution has no metabolism or excretion = all drug remains (graph increases to 100%)
-in blood levels drug is metabolized and excreted (graph goes to zero)

Question 43

Generic concerta

Answer 43

-does not work the same

Question 44

Intuniv

Answer 44

-ADHD drug
-NOT a stimulant
-Guanfacine HCL in polymer MATRIX

Question 45

Guanfacine base

Answer 45

insoluble

Question 46

fumaric acid

Answer 46

-acidifies matrix
-prevents guanfacine base from precipitating

Question 47

Intunivir WITHOUT fumaric acid

Answer 47

-guanfacine precipitates at pH 6.8
-does not fully dissolve

Question 48

Omeprazole

Answer 48

-degrades in acid
-made patients drink baking soda to lower stomach acid
-innovations in enteric coatings
-can be stabilized by basic microenvironments