Predictive stability of dissolution

The use of Predictive Stability tools is growing both within AZ and across the industry. Specifically Accelerated Stability Assessment Program (ASAP) predictions are being used to support extended shelf life claims in regulatory submissions. A recent survey of IQ member companies reported that over 23 countries have accepted ASAP data in clinical submissions and "worldwide" acceptance was claimed in marketing submissions. ASAP studies are stressed short term stability studies focused on the kinetics of chemical degradation with the aim of extrapolating to long term storage conditions. However it also needs to be demonstrated that other stability indicating attributes will not fail specification during the extended shelf life claim. Dissolution is one such attribute specifically relevant for oral solid dosage forms. There is currently a significant gap in the understanding of why dissolution performance can change on storage and current knowledge is very project specific.

In this PhD changes in dissolution performance of both tablets and capsules on storage will be studied from first principles. The project will look to manufacture representative placebo tablet platforms using AZ standard excipients and processes (RC/WG), which will then be fully characterized and subjected to short term stressed conditions focusing on temperature and humidity. Characterization will include disintegration, excipient dissolution, water content, hardness and porosity as well as the possible application of advanced technologies for example nanoCT.