Biopharmaceutics 4 Flashcards
In-vitro dissolution testing models
profile similarity determination
what is considered similar, so…
Comparing immediate release products if test and reference product if more than or equal to 85% dissolution within 15 minutes
so no calculations are require
In-vitro dissolution testing models
profile similarity determination
what happens if the test and reference product are similar?
Calculate the f2 value
if f2 is more then or equal to 50 then it is similar
what do we do if f2 is below 50
more investigation must be initiated to determine the cause of apparent dissimilarity
Table
Apparatus
Dissolution media
Volume of media
Temperature
Sampling points
Units (vessels)
Apparatus: paddle 75 rpm / basket 100 rpm,
Disso media: pH 6.8 phosphate buffer
pH 4.5 acetate buffer
buffer pH 1.2 or 0.1 M HCl,
Media vol: 900 ml,
Temp: 37 °C +/- 0.5 °C,
Sampling points: 5, 10, 15, 20, 30, 45, 60, 120 mins etc,
UNITS: 12
What is the objective of the biopharmaceutics classification system
to predict in-vivo performance of drug products from in-vitro measurements of membrane permeability and aqueous solubility
Benefit of the BCS
drug products may qualify for a waiver i.e. no human studies / clinical trial, save time / money
It can save both time and money – if the immediate release, orally administered drug meets specific criteria, the FDA will grant a waiver for expensive and time-consuming bio-equivalence studies.
This step will reduce timelines in the drug development process and reduces unnecessary drug exposure in healthy volunteers.
AVOIDS UNCESSSARY HUMAN EXPERIMENTS
What are the 4 classes based on
Solubility
permeability
dissolution
( they provide a basis for in vitro- in vivo correlations)
What is in vitro in vivo correlation
A mathematical model that described the relationship between in vitro and in vivo properties of a drug product
so that in vivo properties can be predicated from its in vitro behaviour
Applications of IVIVc
1) early development of drug product and optimisation
2) biowaiver for minor formulation and process changes
3) setting dissolution specifications
BCS criteria
Highly soluble (≤250 ml – bioequivalence study), highly permeable (≥ 90% of dose), rapid dissolving (85% 15m)
Class I
High solubility, high permeability
high absorption, high dissolution + low dose number e.g metoprolol, propranolol
Class II
Low solubility, high permeability,
high absorption, low dissolution + high dose number e.g griseofulvin, phenytoin
Class III
High solubility, low permeability,
low absorption, high dissolution + high dose number e.g cimetidine, acyclovir
CLASS IV
Low solubility, low permeability,
low absorption, low dissolution + high dose number e.g Furosemide, retonavir
Benefits of knowing BCS category of compound
It can save both time and money – if the immediate release, orally administered drug meets specific criteria, the FDA will grant a waiver for expensive and time-consuming bio-equivalence studies.
This step will reduce timelines in the drug development process and reduces unnecessary drug exposure in healthy volunteers.
In early drug development, knowledge of the class of a particular drug is important factor influencing the decision to continue or stop development.
Help pharmaceutical manufacturers to avoid unnecessary human experiments and reduce cost and time of the product development. This is of particular interest in countries with considerably limited health care budget.
Target compounds showing optimal properties.
Limitations of BCS
- Absorption transporters and efflux pumps are not considered
- Drugs undergoing first pass metabolism or secondary metabolism are not factored in appropriate manner.
- Solubility and permeability measurements are loosely defined
- Food effects is not considered
- Chances of misclassification
- It’s based on highest doses but what about smaller doses of same products?
Intended only for immediate release (IR) products that are absorbed throughout GIT.
What is a biowaiver
approval of a drug product without having to conduct an in-vivo bioavailability and / or bioequivalence (BE) study.
Instead of conducting expensive and time consuming in-vivo studies, a dissolution test could be adopted as the surrogate basis for the decision as to whether the two pharmaceutical products are equivalent.
Advantage of biowaiver
avoiding unnecessary human experiments, simplification of time required for product approval, thus reducing the cost of bringing new products to the market.
Which pharmaceutical formulations can be considered for a Biowaiver according to the FDA?
Should contain a Class I drug substance
