Biopharmaceuticals Flashcards
Components of a drug
- Active pharmaceutical ingredient (API)
- Excipients- everything else
Different routes of ingestion
-Oral
-Parenteral (IM/SC/IV)
-Topical vs. transdermal
-intra-mammary
-intranasal
-rectal
-buccal
Oral route
-can be solid, semi-solid (paste/suspensions), oral solution, feed premix (powder)
>think about different timing of drug release and absorption
>solids=longer expiry dates; liquids= short expiry dates
How much API gets absorbed?
-depends on how much of drug gets into the blood stream… Route will effect this (IV greater vs. oral)
**effects bioavailability
Parenteral (IM/SC/IV) route
-usually solution (water-soluble)
-sometimes non-aqueous
-must be sterile
-often irritating; companies will try to modify it the best they can
Topical vs. transdermal routes
-Topical: on top of skin; Transdermal: drug goes through skin into blood
-creams, liquids, gels, patches
-intended for local effect only
Intra-mammary route
-suspension
-stay in the teat/udder
Intranasal route
-liquid, aerosolize/nebulize (convert liquid to fine particles)
-drug either stays in nostril/head vs. nebulizer results in drugs reaching alveoli
Rectal route
-suppository
Buccal route
-fast dissolving tablet or paste
-absorbed through cheek epithelium which helps to avoid first pass through the hepatic metabolism
-need to make sure that it isn’t swallowed (difficult in animals)
Why do drugs need excipients?
-Can be used to change Cmax, Tmax, AUC. Can be used to modulate levels that reach systemic circulation
-avoid poor taste and irritation of GI mucosa
-can be used to modulate levels that reach systemic circulation
-stability of API in dose form
-help API stay on skin in topical route
-help API penetrate the skin in transdermal
Excipients of oral drugs
-binding agent
-coating or capsule
-flavouring agent
Binding agent purpose in oral meds
-delays disaggregation (break down tablet) and dissolution (solubilizes aPI) which ensures it makes it into the intestinal cell
Coating/capsule in oral meds
-protect API from stomach acid
-decrease irritation in proximal GI tract
-delay timing of absorption
Flavouring agent in oral meds
increase palatability
Excipients in parenteral injected meds
-pH adjuster
-salt or chelating agent
-preservative
pH adjuster in parenteral meds
-makes injection less irritating
-increases solubility of API allowing for smaller injection volume
-enhances stability of the API in solution
Salt or chelating agent in parenteral injection
-alters API solubility
-determines how long before APi is released
-vasoconstriction
Preservative in parenteral drugs
-maintain sterility
What is the difference between longer release drugs and other drugs on the market?
Longer release drugs will often have more of the active ingredient present than any other drug form (higher dose 100mg compared to slower release 50mg)
Pioneer drugs
-the original drug that came to market
-high cost
-requires all clinical, safety and efficacy studies
-Patent allows for exclusive marketing and when patent runs out, price will drop
Generic drugs
-copies of the pioneer drug
>proven safety and efficacy of pioneer drug so the generic drugs don’t need to reproduce studies but still need to prove quality
Compounded drugs
-pharmacy makes up the drug product… but not an approved drug product
Generic drug approval process
- Test for manufacturing and chemistry/drug product quality. Requires same potency (strength or concentration), purity (API, no excess impurities), stability and sterility
- Clinical efficacy and safety- must be same strength and dosage form, and demonstrate bioequivalence
Bioequivalence between pioneer and generic
Generic drug has equal plasma concentrations to pioneer drug resulting in clinical efficacy and safety (bioavailability and absorption)
Bioequivalence
When the rate and extent of absorption of two pharmaceutically equivalent formulations of drugs (pioneer or generic) are sufficiently similar, within allowable limits, when administered under similar experimental conditions
Clinically interchangeable
When a generic drug has the same strength, dosage form, and bioequivalence!
Drugs with equal amounts of identical medicinal ingredients in comparable dosage forms
Does not mean they have the same non-medicinal ingredients- as long as varying non medicinal ingredients doesn’t influence the absorption characteristics of the active ingredient
How to prove bioequivalence?
-Blood level Crossover study (2 groups, 2 treatments) to compare generic and pioneer products
>each animal gets both products with a washout period in between (10x half life)
>collect multiple blood samples (need early and late times) to determine plasma concentrations
>create concentration-time profiles (AUC, Cmax, Tmax)
What times do blood samples need to be collected over time?
Early: enough to capture absorption/Cmax
Late: At least 3x half life beyond Tmax
Compounding
-combining or mixing multiple ingredients (at least one has to be a drug) to create a final product in an appropriate dosing form
Why use compounded drugs?
1.available formulations are not appropriate for a specific patient- diluted formulation for very small animals
- Improve client compliance (palatability; non-oral formulation)
- no approved drug product commercially available (requires bulk ingredients)
-Ex. Cisapride, apomorphine, KBr
FDA rules on compounded drugs
-used to treat an unmet therapeutic need or reduce animal suffering
-cause no harm to treated animal
-do not result in therapeutic failures
-do not result in violative drug residues (food animals)
Order of drug choice
- approved vet drug on label
2.approved vet drug extra label
3.approved human drug
4.compounded drug- from approved vet drug - compounded drug- from approved human drug
- compounded drug from active pharmaceutical ingredient
Compounding concerns
- purity
- potency
- Stability of compounded formulation
- Pharmacokinetic changes due to formulation
Purity of compound drug
-quality of drug- drug that is present is supposed to be there, no other drugs should be there
Potency of compounded drug
-quantity of drug need to line up with accuracy of label quantity
**manufactured drug concentration must be within 10%
Meloxicam compounding example
-looked at 19 compounded products
-actual concentrations of meloxicam was from 37-132%
-majority of them did not meet drug potency!
Stability of compounded formulation
-hydrolysis- if it comes dry, needs to stay dry
-oxidation-change due to light or O2
-consistency- precipitates
-expiry date- 25% of time left on original expiry date. Usually very short.
*water-based compounds: 14 days
*Oil-based compounds: 180 days
Pharmacokinetic changes due to formulation
Compounded drugs can have alterations in terms of:
-Absorption (oral, transdermal)
-bioavailability
Compounded Transdermal products
-just because a pharmacy can make a gel or patch, but it does not mean it will be absorbed
>results can vary between individuals
>not uniform between pharmacies
**need to explain efficacy
What to tell clients about compounded drug products?
- Explain use for specific patient (different strength or route of administration is needed OR no approved drug is available)
- Have a method of assessing efficacy of compounded drug
3.Get informed consent from client, and document in medical record
**Compound and generic are not the same thing!!!
**do not use because it is cheaper!!
DIN
Drug ID number= approved drug
