Effects of excipients on the crystallization of pharmaceutical compounds during lyophilization

Abstract

Many drug compounds fail to crystallize during lyophilization, producing the less stable amorphous form. During a study to screen various excipient materials for their effect on crystallinity, the addition of certain excipients (glycine, alanine, serine, methionine, urea, and niacinamide) to aqueous solutions of atropine sulfate, cefoxitin sodium, cefotaxime sodium, cefazolin sodium, doxycycline hyclate, procainamide hydrochloride, lactose, and polyvinylpyrrolidone induced these compounds to crystallize during the freeze drying process. Crystallinity was determined by microscopic examination under polarized light. This method of producing a crystalline freeze dried solid could prove useful in the production of stable, cost-effective freeze dried pharmaceuticals.