摘要：

The pharmaceutical literature cites many examples which indicate that hard gelatin capsule brittleness is a function of moisture content. Likewise, brittleness can be correlated with relative humidity. In this study, brittleness of empty capsules was noted at relative humidities below 40%. Mexitil capsules exhibited a similar profile, suggesting that relative humidity in the vapor phase is an important factor that can be monitored and controlled. It is known that moisture will redistribute between the various components in a given system until a single relative humidity is attained in the vapor phase. Thus, a priori prediction of the value of this thermodynamic variable for known conditions will allow prediction of capsule brittleness. For a closed system, the final value is intimately dependent upon the affinity of the various materials for water. As such, the sorption-desorption moisture transfer (SDMT) model, which is based on isotherms for the respective materials, was employed to estimate the final relative humidity for the Mexitil/gelatin capsule system. Results are presented that demonstrate the general applicability of the SDMT model for predicting the incidence of brittleness problems, as well as selecting optimal initial loss on drying (LOD) values for the empty gelatin capsules and the formulation to ensure the absence of brittleness.

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