Development of dissolution tests and their biomimetic value
Prediction of drug substance pharmacokinetics
Consideration of pKa and sites of absorption
Value of iViV correlations – regulatory viewpoint
Biostudy results vs. statistical requirements
Dissolution testing has been around for some 50 years. During that period we have put a man on the moon, we have made huge advances in computer software and hardware and have moved from vinyl through open reel tapes, cassettes, CD's and mpeg in terms of recording, and yet most dissolution testing is carried out on essentially the same equipment that was introduced into the Pharmaopias back in the '70's. However the regulatory authorities are demanding more and more data and interpretation of that data derived from equipment that was never intended as anything beyond a relatively crude quality control technique.
It is not surprising therefore that chemists, formulators and regulatory staff are still battling to provide answers to many of the regulatory demands. In order to meet these challenges it is necessary to understand the limitations of the equipment and the dosage form-equipment artifacts that can be created. Unfortunately very often dissolution testing suffers from the classic problem of silo thinking. The analytical chemist (dissolution scientist) looks at the test as a physicochemical process, often not understanding the principles involved in formulating products and the formulator looks at the results as a set of numbers which may or may not satisfy what may appear to be arbitrary requirements of QA or regulatory departments. This is all without even starting on the question as to the relevance or correlation with what is actually happening to the product in the patient.
This course will attempt to tear down the walls of these silos. We will be looking at dissolution from the limitations of the testing procedures, the way different formulations behave in test procedures through to the concepts of pharmacokinetics and the regulatory requirements for submission for marketing authorization.
by Malcolm Ross, President at Generapharm, Switzerland
How to design a bioequivalence study
The statistical design needed to getregulatory approval
The role of dissolution studies inscreening formulations and as a regulatory requirement
In vivo-In vitro correlation:connecting the dissolution data to pharmacokinetics
- About the predictive power of pilotstudies and fed stat
- The requirements for studies in fasting and fed state
How to develop dissolution tests and how to interpret them
About the use of dissolution studies to obtain biowaivers
- An understanding of the relationship between formulation and bioavailability
- A fundamental knowledge of drug absorption and its effect on dissolution and pharmacokinetics
An appreciation of what to look forwhen auditing a biostudy house in terms of validation
Project management skills in terms oftiming and planning of biostudies