Temperature/Humidity Sensitivity of Sustained‐Release Formulations Containing Kollidon® SR

Abstract

The effects of temperature and humidity on tablets containing Kollidon® SR have been evaluated using diphenhydramine HCl as a model drug. Exposure of tablets to ICH accelerated stability condition (40°C/75%RH) in an open dish resulted in rapid increases in tablet hardness, accompanied by step‐wise decreases in dissolution rate. Such a change can be observed as fast as an hour upon exposure. The tablet matrix appears to rapidly absorb atmospheric moisture, as demonstrated by tablet weight gain and moisture adsorption isotherms. Exposure to 25°C/60%RH similarly resulted in increases in tablet hardness, although with minimal impact on dissolution. Potential implications of such rapid moisture uptake during aqueous film‐coating were further evaluated by spraying either water or an Opadry solution in a coating pan. Exposure of Kollidon SR tablets to the aqueous coating process indeed resulted in noticeable changes in both hardness and dissolution. Application of the Opadry solution appears to affect tablet behavior to a lesser degree, compared to water, most likely due to protection via formed barrier film. Attention needs to be paid to the extreme sensitivity of Kollidon SR matrix tablets to temperature and moisture during product development.