Amphiphilic Block Copolymer as a Crystal Habit Modifier

Abstract

The purpose of this study is to evaluate amphiphilic block copolymers, a new class of additives, for the habit modification of pharmaceuticals. The additive chosen is poly(ethylene glycol)- block -poly(lactic acid) (PEG- b -PLA). The model compound chosen is tolazamide, an oral hypoglycemic pharmaceutical agent. Crystallization was carried out in aqueous media by pH adjustment, with or without additives. PEG- b -PLA was found to be very effective in modifying the crystal habit of tolazamide. The habit changed from a needle shape to a plate shape at a concentration of 12.5 μg/mL. This change in habit required both blocks and could not be achieved in the presence of either block alone. A small amount of copolymer (0.55% weight) was found on/in tolazamide particles crystallized in the presence of 30 μg/mL of copolymer. Washing the crystals with toluene effectively removed the copolymer. It is thus concluded that the block copolymer is mainly adsorbed on the crystal surface(s) rather than being incorporated into the lattice of tolazamide crystals. The recrystallized tolazamide is of the same crystal form as that of the original solid, regardless of the concentration of the copolymer used.