10 – Biopharmaceutics & Drug Types Flashcards
1
Q
Drug product is comprised of different components
A
- Active pharmaceutical ingredients (API)=’drug substance’
- Everything else (‘excipients’)
2
Q
Oral route: dosage forms
A
- Solid
- Semi-solid
- Oral solution
- Feed premix
*usually have longer expiry dates
3
Q
Capsule vs. pill/tablet
A
- Tablets can be split
4
Q
Parenteral (‘injectable w/needle’) (IM/SC/IV) route: dosage forms
A
- Usually solution (water-soluble)
- Sometimes non-aqueous (ex. oil)
**needs to be sterile
5
Q
Topical (stay on skin) vs. transdermal (through the skin) route: dosage forms
A
- Cream
- Liquid
- Gels
- Patches
**intended for local effect
6
Q
Intra-mammary (IMM) route: dosage forms
A
- Suspension
7
Q
Intranasal (IN) route: dosage forms
A
- Liquid
- Aerosolize/nebulize (convert liquid to fine particles)
8
Q
Rectal route: dosage forms
A
- Suppository
9
Q
Buccal route: dosage form
A
- Fast dissolving tablet or paste
**avoids first pass (hepatic) metabolism (BUT make sure it isn’t swallowed)
10
Q
Why not just administer the active pharmaceutical?
A
- Just dosing API probably won’t MAXIMIZE its efficacy or safety
- Ex. how much reaches systemic circulation, stability, taste
11
Q
If use a drug product with a delayed absorption what changes?
A
- Usually C max
- Tmax
- AUC (elimination half-life)
12
Q
Oral administration excipients
A
- Binding agent
- Coating or capsule
- Flavouring agent
13
Q
Oral administration: binding agent
A
- Delays DISAGGREGATION (break down tablet) and DISSOLUTION (solubilizes API)
- *both necessary to permeate intestinal cell
14
Q
Oral administration: coating capsule
A
- Protect API from acid in stomach
- Decrease irritation in proximal GIT
- Delay timing of absorption
15
Q
Parenteral injection (IM, SC, IV) excipients
A
- pH adjuster
- salt or chelating agent
- preservative
16
Q
Parenteral injection: pH adjuster
A
- makes injection less irritating
- increase solubility of API
- enhance stability of API in solution
17
Q
Parenteral injection: salt or chelating agent
A
- alters API solubility
- determines how long before API is released
- vasoconstriction: impact on absorption?
18
Q
Parenteral injection: preservative
A
- maintain sterility
19
Q
Long story short of biopharmaceutics
A
- formulation matters
- different forms of same API can have BIG differences
- messing with formulation changes the drug product
20
Q
Pioneer drug product
A
- innovator
- first one that came to market
21
Q
Generic drug product
A
- copy of the pioneer
22
Q
Compounded drug product
A
- making up a drug product in the clinic, but not approved
23
Q
What is the point of generic drugs?
A
- More drug product availability
- More competition = decrease prices
- Only once pioneer drug patent has expired
24
Q
How come pioneer drugs are more expensive?
A
- High costs for initial drug approval
- Patents allow for exclusive market ($$$)
- When patent runs out=price typically drops
25
How come generic drugs are cheaper?
- ‘proven’ safety and efficacy of pioneer drug
- NOT required to reproduce efficacy and safety studies that pioneer did
26
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
27
Clinical efficacy and safety of generic drugs
- Must be same STRENGTH and DOSAGE FORM
- Demonstrate BIOEQUIVALANCE with pioneer product
- *’clinically interchangeable’
28
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
29
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
30
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)
31
If below 80% CI: blood-level study
- Worried about efficacy
32
If above 80% CI: blood-level study
- Worried about safety
33
Compounding
- Combining or mixing multiple ingredients (at least one is a drug) to create a final product in an appropriate dosing form
34
Why use compound drugs?
1. Available formulations are NOT appropriate for a specific patient (diluted form for very small animals)
2. Improve client compliance (more palatable oral product, non-oral formulation)
3. No approved drug product commercially available
**COST is NOT a valid reason
35
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)
36
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
37
Compounding concerns
1. PURITY of compound drug
2. POTENCY of compounded drug
3. Stability of compounded formulation
4. Pharmacokinetic changes due to formulation
38
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
39
Potency of compound drug
- ‘quantity’ of drug
- ACCURACY with label quantity
- Manufactured drugs: concentration must be within +/- 10%
40
Meloxicam example: compounding
- Tested compounded products
- Potency: 37-132% claimed concentration
- *what batch did you get? You don’t know!
41
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)
42
Compound stability case: in UK with epidural injection
- ‘preservative free’
- Fungal contamination of ‘sterile’ MPA vials
43
Pharmacokinetic changes due to formulation
- Absorption (oral, transdermal)
- Bioavailability
44
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
45
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
46
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
