Relation Between Polymorphic Transformation Pathway During Grinding and the Physicochemical Properties of Bulk Powders for Pharmaceutical Preparations

Abstract

The polymorphic transformation pathway during grinding of cephalexin (CEX), chloramphenicol palmitate (CPP) and indomethacin (IMC) were investigated. CEX was converted into noncrystalline solid at room temperature. The meta-stable forms B and C CPP was transformed into stable form A at room temperature. IMC was transformed into noncrystalline solid during grinding at 4°C, but it transformed into meta-stable form a during grinding at 30°C. The melting point (mp) of CPP and IMC were about 90°C and 160°C, respectively. CEX does not have the mp, but have the decomposition point at 190°C. The mp of CEX is higher than the decomposition point. The order of the mp for these drugs is CPP < IMC < CEX. The proportional relation between the mp and the glass transition point of the drugs had reported, therefore, in general the higher mp material has the higher glass transition point. The order of the stability for a noncrystalline solids of these drugs is CPP < IMC < CEX. The noncrystalline solid of CEX is very stable at 35°C under lower than 66% of relative humidity. The noncrystalline solid of CPP was very unstable at about 20°C, therefore, it transformed into a crystalline form very rapidly. The noncrystalline solid of IMC was stable at 4°C, but it was unstable at 30°C, therefore, after grinding it transformed into a form. These results suggest that there is a very important relation between the transformation pathway of the crystalline form during grinding and the physicochemical properties. The transformation pathway is controlled by the stability of noncrystalline solid and the presence of meta-stable crystalline form.