Screening of Incompatibility between Drug and Excipient
An important step in the design and development of optimal formulations for a pharmaceutical product is the selection of excipients to be used together with the active ingredient. Especially for low dose tablets there will be a significant number of points of interaction between the API and the different excipients. Hence, it is vital to select excipients that not only fulfil manufacturing and product performance demands but also to avoid any kind of incompatibility.
The traditional way of selecting these components is to manufacture a number of different prototype formulations, examine their handling and processing behaviour and then initiate a stability study on the best alternatives with read out after several months if no accelerated conditions are applied.
- Time is always an issue and an iterative “trial and error” approach might mean a waste of several months in case alarming degradation is seen after storage at normal conditions.
- Applying too accelerated conditions introduces another disadvantage since there will be a significant risk of obtaining false negatives due to alternative degradation mechanisms.
The Adroit alternative is here to exchange conventional stability studies with ultrasensitive microcalorimetrical investigation providing read outs of incompatibility tendencies within a few days.
By simultaneously investigating different API:excipient combinations at relevant conditions, e.g., at 40°C and 75%RH, it was possible to identify and point out a single incompatible excipient already after a few days of experiment, saving almost 3 months in development time which made it possible to replace this excipient already at an early development stage.