Exploring the Myth of Inert Excipients
Stable active pharmaceutical ingredients (APIs) represent a critical success factor for drug formulation for four main reasons.
Firstly, the potential instability of APIs can represent a critical threat to patient safety. This risk can be generated through the decline in the actual dosage of the drug as its content degrades over time, or via the creation of toxic degradation products.
Secondly, the stability of an API is a prerequisite for regulatory acceptance of the drug. Thirdly, greater API instability reduces the potential shelf-life of a drug, risking excessive wastage and damaging revenues and profits if demand is lower than anticipated.
Finally, API instability can increase the complexity and cost of drug storage requirements, such as extra cooling, which also harms the economic viability of the drug, increasing costs and eroding convenience for both physicians and patients.
The factors that cause an API to become unstable include, but are not limited to:
- Exposure to heat and/or changes in temperature
- Exposure to moisture
- pH sensitivity
- Biological contamination
- Light sensitivity
- Interaction with other formulation components
The relevance of each factor is dependent upon the API used. This also means that preventive measures have to be considered on a case-by-case basis. However, exposure to heat, moisture and oxidation are factors that are known to induce instabilities across a broad range of APIs.
This white paper examines the potential impact of poor API stability in solid dose drug development, explores the causes of instability and explains how excipients can help in creating stable formulations. Finally, it also presents some case studies to illustrate their potential effectiveness.
Authors: Hans-Leonhard Ohrem, Adela Kasselkus