Use of isothermal microcalorimetry in pharmaceutical preformulation studies

Excipient compatibility of a new chemical entity was assessed using an isothermal microcalorimeter. Mixtures of an active pharmaceutical ingredient with a primary amine group and excipients were prepared in a 1:1 ratio and compatibility monitored by exposing to 50, 60 and 70°C in presence of 200 mL of water. The new chemical entity, a primary amine, reacted with reducing sugars such as lactose and resulted in a brown discoloration. This reaction is the Maillard type condensation reaction between amines and reducing sugars. The rate of reaction was dependent on the temperature with rapid degradation at higher temperatures. No other incompatibility was apparent between the primary amine and other excipients This revised version was published online in July 2006 with corrections to the Cover Date.