Accelerated physical stability testing and long-term predictions of changes in the crushing strength of tablets stored in blister packages

Abstract

A physical model is presented which permits the amount of sorbed moisture and the crushing strength of compressed tablets stored in blister packages to be predicted based on a knowledge of: (1) tablet moisture sensitivity; (2) package moisture permeability; and (3) relative humidity storage conditions. The tendency of tablets to sorb water can be characterized in approximately one week by storing unprotected tablets at several relative humidities. This information, in combination with package moisture permeability data, permits changes in tablet crushing strength and sorbed moisture to be made under a variety of storage and packaging conditions. These predictions are useful in establishing long-term stability testing protocols. They are also useful in predicting what tablets stored in blister packages might reasonably be expected to experience in the market place where short-term and long-term oscillating conditions are likely to occur. Theoretical predictions based on the physical model indicate that, in general, tablets stored in relatively permeable blister packaging materials will be protected from large, short-term humidity fluctuations of several hours or days. Long-term fluctuations due to monthly and seasonal variations in humidity will be important. Tablets stored in relatively permeable blister packages at relative humidities representative of marketplace conditions can be expected to experience humidities varying between 30% and 70% while less permeable packages will show less variation. This suggests that oscillating unprotected tablets between 30% and 70% relative humidity every 2–3 days for a 2–3-week period may produce changes similar to those observed for tablets stored in marketed blister packages. Tablets tested using these conditions showed changes in crushing strength similar to those packaged in blister packages and used in a 3-year field study. The theoretical predictions and experimental results emphasize the importance of matching the dosage formulation characteristics to the package material and testing conditions. In this way, a more rational selection of packaging material and testing protocols can be made.