Identification of stabilizing and destabilizing effects of excipient-drug interactions in solid dosage form design

Abstract

The compatibility of pyridoxal hydrochloride with various tableting excipients has been investigated by isothermal stress testing of multicomponent mixtures and by differential scanning calorimetry (DSC) screening of binary drug excipient mixtures. A Plackett-Burman factorial design was used to conduct the isothermal stress testing experiment. Elevated moisture and temperature were found to be the dominant destabilizing factors. The factorial design experiment also revealed chemical incompatibilities with mannitol, lactose and corn starch. Simultaneously, the strong stabilizing influences of various cellulose derivatives and colloidal silicone dioxide were identified. It appears that these excipients function as moisture scavengers, thus decreasing the amount of free water available for interaction with pyridoxal hydrochloride. The major incompatibilities were also detected by DSC screening. The study demonstrates the value of employing a compatibility screening procedure capable of detecting both positive and negative drug-excipient interactions.