Lecture 1: Innovations Flashcards
Vaccine innovations: types of vaccines
-mRNA vaccine
-vector vaccine
-protein subunit vaccine
-whole killed vaccine
ADHD drugs
-methylphenidate
-amphetamine
-intuniv (nonstimulant)
Methylphenidate drugs
-ritalin and concerta
-Daytrana patch
Dissolution Testing
-method for insuring quality of tablets and capsules
-only method that can be lonked to blood levels and bioavailability
5 Methods for insuring quality of tablers and capsules
- dissolution testing
- Assay
- impurities
- content uniformity
- water
disintegration vs Dissolution
- Disintegrate FIRST
- then DISSOLVE
Tablet must first ehat before the drug caan dissolve?
disintegrate
Dissolution from dosage forms
-dissolution of drug in GI fluid needed before absorption can occur
DIssolution of drugs with high solubility
-few formulation problems
Dissolution of drugs with low solubility
-absorption rate may be governed by dissolution rate
-if dissolution too slow = absorption bad
Dissolution experiment
-place tablet in apparatus
-measure rate of dissolution
dissolution tests measure
rate of release of drug from tablet
Poorly soluble drugs can dissolve under:
-physiological conditions if its dose is sufficiently SMALL
dose solubility volume
-may be more relevant than solubility alone
-even poorly soluble drugs can completely dissolve if the dose is small enough
High solubilty definition
-largest human dose is soluble in 250mL or less of water throughout the physiological range of 1-8 at 37C
Low solubility drug definition
-more than 250 mL of water needed to dissolve the largest dose
-any pH at 37C
Why 250mL?
-estimated minimum gastric volume available
-based on volume of water recommended for ingestion during administration
Bioavailability depends on:
-having drug in solution
-drug permeabilty
Jejunal permeability
-high
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
