For an alternative view on combination drugs, go to http://www.pharmtech.com/unstable
What are the stability issues?Stability problems in combination products can be attributed to three types of interaction:
The incompatibility interactions are often facilitated by the close contact between drugs and excipients. There are other factors such as the pH of the formulation microenvironment, temperature and moisture — all of which initiate and catalyse chemical reactions.
The instability of combination drugs is manifested in various forms that can be broadly classified into three groups: physical instability, which includes changes in physical appearance (e.g., colour, precipitation, hardness, etc.); chemical instability — variation in drug content and impurities; and functional instability — changes in the drug release pattern.
We can address incompatibility challenges
Significant research has been conducted to understand the root cause of drug incompatibility issues. The vast amount of literature and knowledge on the structural and chemical properties of drugs and excipients can help development teams to assess possible incompatibilities and make a development strategy that addresses such challenges effectively.
As previously mentioned, the instability of combination products is mainly the result of incompatibility between formulation components; for example, drug and excipients. A systematic development strategy is the first step to detect any potential compatibility issues and accordingly design the product. It is, therefore, possible, to safely develop a combination drug product that is stable and has a sufficient shelf-life, so long as the following key factors are considered: preformulation and degradation; dosage form selection; packaging development; preclinical studies; and product specification.