10 – Biopharmaceutics & Drug Types Flashcards
Drug product is comprised of different components
- Active pharmaceutical ingredients (API)=’drug substance’
- Everything else (‘excipients’)
Oral route: dosage forms
- Solid
- Semi-solid
- Oral solution
- Feed premix
*usually have longer expiry dates
Capsule vs. pill/tablet
- Tablets can be split
Parenteral (‘injectable w/needle’) (IM/SC/IV) route: dosage forms
- Usually solution (water-soluble)
- Sometimes non-aqueous (ex. oil)
**needs to be sterile
Topical (stay on skin) vs. transdermal (through the skin) route: dosage forms
- Cream
- Liquid
- Gels
- Patches
**intended for local effect
Intra-mammary (IMM) route: dosage forms
- Suspension
Intranasal (IN) route: dosage forms
- Liquid
- Aerosolize/nebulize (convert liquid to fine particles)
Rectal route: dosage forms
- Suppository
Buccal route: dosage form
- Fast dissolving tablet or paste
**avoids first pass (hepatic) metabolism (BUT make sure it isn’t swallowed)
Why not just administer the active pharmaceutical?
- Just dosing API probably won’t MAXIMIZE its efficacy or safety
- Ex. how much reaches systemic circulation, stability, taste
If use a drug product with a delayed absorption what changes?
- Usually C max
- Tmax
- AUC (elimination half-life)
Oral administration excipients
- Binding agent
- Coating or capsule
- Flavouring agent
Oral administration: binding agent
- Delays DISAGGREGATION (break down tablet) and DISSOLUTION (solubilizes API)
- *both necessary to permeate intestinal cell
Oral administration: coating capsule
- Protect API from acid in stomach
- Decrease irritation in proximal GIT
- Delay timing of absorption
Parenteral injection (IM, SC, IV) excipients
- pH adjuster
- salt or chelating agent
- preservative
Parenteral injection: pH adjuster
- makes injection less irritating
- increase solubility of API
- enhance stability of API in solution
Parenteral injection: salt or chelating agent
- alters API solubility
- determines how long before API is released
- vasoconstriction: impact on absorption?
Parenteral injection: preservative
- maintain sterility
Long story short of biopharmaceutics
- formulation matters
- different forms of same API can have BIG differences
- messing with formulation changes the drug product
Pioneer drug product
- innovator
- first one that came to market
Generic drug product
- copy of the pioneer
Compounded drug product
- making up a drug product in the clinic, but not approved
What is the point of generic drugs?
- More drug product availability
- More competition = decrease prices
- Only once pioneer drug patent has expired
How come pioneer drugs are more expensive?
- High costs for initial drug approval
- Patents allow for exclusive market ($$$)
- When patent runs out=price typically drops
How come generic drugs are cheaper?
- ‘proven’ safety and efficacy of pioneer drug
- NOT required to reproduce efficacy and safety studies that pioneer did
What do generic drugs need to be approved?
- Manufacturing and chemistry (PRODUCT QUALITY)
o Potency
o Purity
o Stability, sterility, etc - Clinical efficacy and safety
Clinical efficacy and safety of generic drugs
- Must be same STRENGTH and DOSAGE FORM
- Demonstrate BIOEQUIVALANCE with pioneer product
- *’clinically interchangeable’
Bioequivalence
- Rate and extent of absorption is the same between two pharmaceutically equivalent formulations of drugs within ALLOWABLE LIMITS when under similar experimental conditions
- *assumption: equal plasma concentrations=equal clinical efficacy and safety
- **Cmax and AUC=same
Pharmaceutically equivalent
- Two drugs that contain IDENTICAL AMOUNTS of IDENTICAL MEDICINAL INGREDIENTS in comparable DOSAGE FORMS
- Ex. if pioneer drug is tablet, generic version cannot be a solution
- *doesn’t necessarily contain the same non-medicinal ingredients
How to PROVE bioequivalence: blood-level study
- Each animal gets both products with a ‘washout period’
o 10x half life to avoid drug carry over into next period - Dosing same animal twice reduces inter-individual variability
- Collect multiple blood samples over time
- Determine plasma concentrations (REQUIRES VALIDATED ANALYTICAL METHOD
- *look at ratio of AUC and Cmax (needs to be between 0.8-1.25=80% confidence intervals)
If below 80% CI: blood-level study
- Worried about efficacy
If above 80% CI: blood-level study
- Worried about safety
Compounding
- Combining or mixing multiple ingredients (at least one is a drug) to create a final product in an appropriate dosing form
Why use compound drugs?
- Available formulations are NOT appropriate for a specific patient (diluted form for very small animals)
- Improve client compliance (more palatable oral product, non-oral formulation)
- No approved drug product commercially available
**COST is NOT a valid reason
FDA rules on compound drugs
- Used to treat an UNMET therapeutic need or reduce animal suffering
- Do NOT cause harm to treated animal
- Do NOT result in therapeutic failures
- Do NOT result in violative drug residues (food animals)
Compounded drug ‘ladder’
- Approved vet drug: on label
- Approved vet drug: extra-label
- Approved human drug
- Compounded drug: vet drug
- Compounded drug: human drug
- Compounded drug: active pharmaceutical ingredient
Compounding concerns
- PURITY of compound drug
- POTENCY of compounded drug
- 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 there if not supposed to be
Potency of compound drug
- ‘quantity’ of drug
- ACCURACY with label quantity
- Manufactured drugs: concentration must be within +/- 10%
Meloxicam example: compounding
- Tested compounded products
- Potency: 37-132% claimed concentration
- *what batch did you get? You don’t know!
Stability of compounded formulation
- Hydrolysis (comes dry=keep it dry)
- Oxidation (pink or amber colour change)
- Consistency (precipitates, settling out)
- Expiry date? (25% of time left on original expiry date)
- *if say water-based compound good for 3-6months=BS! (usually put 14 days)
Compound stability case: in UK with epidural injection
- ‘preservative free’
- Fungal contamination of ‘sterile’ MPA vials
Pharmacokinetic changes due to formulation
- Absorption (oral, transdermal)
- Bioavailability
Compounded transdermal products
- *just because there is a gel or patch with API in it does NOT mean it will be absorbed
- Some APIs will NOT permeate the skin
- Results vary BETWEEN and WITHIN patients
- Products no uniform between pharmacies
What to tell your clients about a compound drug product
- Explain why you are prescribing it (SPECIFIC PATIENT, no approved drug available)
- Have a method of assessing efficacy
- Get INFORMED CONSENT and DOCUMENTATION IN MEDICAL RECORD
What to NOT tell your client about a compound drug product
- Call it a ‘generic version’ or ‘the same thing’
- Use it strictly because it’s cheaper
