Polymorphic Transformation of Some Drugs Under Compression

Abstract

The existence of various crystalline forms in drugs is a phenomenon frequently encountered (about 40% of the USP XX tablet monographs with dissolution tests are concerned with such compounds). Some studies concerning trituration or grinding of polymorphs have been published; surprisingly little information is available on the transformation under compression, although of great relevance. In this work, thirty-two drugs known to exist as polymorphs were submitted to a trituration test for possible transitions. Out of the eleven transforming substances (approximately 34%), three model drugs, namely caffeine, sulfabenzamide and maprotiline hydrochloride were chosen for tabletting tests. Differential scanning calorimetry and hot stage microscopy were used to investigate polymorphic changes on the upper and lower surfaces, middle region and side of the compacts. The relationships between the extent of transformation and the compression pressure, and the energy of compression were examined, as well as the effect of drug particle size.