Differential scanning calorimetry in compatibility testing of picotamide with pharmaceutical excipients

摘要

Differential scanning calorimetry with the support of X-nv powder diffractometry was used as a screening technique for testing the compatibility of picotamide (4-methoxy-N,N'-bis(3-piridinylmethyl)-1,3-benzenedicarboxamide, in the dehydrated form with various pharmaceutical excipients for solid dosage forms. The effect of dry grinding. wet grinding (i.e. kneading) and ageing on drug-excipient blends in the I:I (by weight) ratio on physicochemical and chemical stability of the drug was investigated. Chemical compatibility was in general observed with exception of combinations with tartaric and ascorbic acid, where acid/base interactions induced by heating were responsible for the drug degradation evidenced by the profound modification of the thermal effects of individual components. Analogous modifications (i.e. loss of melting peak of the drug) in mixtures with polyvinylpyrrolidone were due to amorphization of picotamide with no substantial alteration of its chemical integrity. Physical compatibility was seen in the systems with microcrystalline cellulose, corn starch, hydroxypropylmethylcellulose and hydroxyethylcellulose where dehydrated picotamide was stable except under wet grinding conditions. in combinations with sodium carboxymethylcellulose. veegum and arabic gum solid-state phase transformation of dehydrated picotamide to monohydrate occurred also by simple blending. probably because of the weak interaction between excipient and the associated water. (C) 1998 Elsevier Science B.V. [References: 15]