Lecture 1: Innovations Flashcards by Brooke Thornburg

Vaccine innovations: types of vaccines

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

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ADHD drugs

-methylphenidate
-amphetamine
-intuniv (nonstimulant)

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Methylphenidate drugs

-ritalin and concerta
-Daytrana patch

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Dissolution Testing

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

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5 Methods for insuring quality of tablers and capsules

dissolution testing
Assay
impurities
content uniformity
water

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disintegration vs Dissolution

Disintegrate FIRST
then DISSOLVE

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Tablet must first ehat before the drug caan dissolve?

disintegrate

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Dissolution from dosage forms

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

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DIssolution of drugs with high solubility

-few formulation problems

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Dissolution of drugs with low solubility

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

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Dissolution experiment

-place tablet in apparatus
-measure rate of dissolution

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dissolution tests measure

rate of release of drug from tablet

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Poorly soluble drugs can dissolve under:

-physiological conditions if its dose is sufficiently SMALL

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dose solubility volume

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

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High solubilty definition

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

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Low solubility drug definition

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

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Why 250mL?

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

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Bioavailability depends on:

-having drug in solution
-drug permeabilty

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Jejunal permeability

-high

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permeability determined by:

-90% or more of drug absorbed

Least rigorous dissolution test for drugs with:

-HIGH solubility
-HIGH permeability

Rigorous dissolution testing is needed for drugs with:

-HIGH solubility
-LOW permeability

the most rigorous testing is needed for drugs with:

-LOW solubility
-HIGH permeability

-theses are BCS class 2 drugs

BCS class 2 drugs

-LOW solubility
-HIGH permeability

Methylphenidate

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

Methylphenidate USP

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

Methylphenidate SR

-sustained release -utilize polymers -matrix and coated beads

Metadate CD

-extended release beads -medium: water

extended release beads

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

Methylphenidate vs metadate dissolution rate

-methyl plataues and requires another dose -metadate keeps increasing

Film Coating steps

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

coating pans

-accelacota -grover -vector

Fluid Bed coating

-blows hot air to circulate solvent particles to coat tablet

Coating Process

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

Nozzles

-liquid feed -sometimes with air on either side

Polymers for film coating: NONENTERIC

-HPMC -Methyl hydroxyethylcellulose -Ethylcellulose -HPC

ENTERIC polymers for coating

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

Matrix tab;et

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

Elementary Osmotic Pump (EOP) in CONCERTA (OROS)

-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

Single chamber oros

-water comes in and pushes drug MOLECULES out

Double chamber Oros

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

Dissolution rates of methylphenidate vs oros

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

Dissolution vs blood levels

-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)

Generic concerta

-does not work the same

Intuniv

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

Guanfacine base

insoluble

fumaric acid

-acidifies matrix -prevents guanfacine base from precipitating

Intunivir WITHOUT fumaric acid

-guanfacine precipitates at pH 6.8 -does not fully dissolve

Omeprazole

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