An ester derivative of the drug gabapentin: pH dependent crystal stability

Gabapentin solutions with different pHs were prepared and slow crystallization was allowed to occur. Different crystalline forms were obtained at pHs up to 7, whereas alkaline media (pH 9) gave rise to an amorphous product. A new crystal structure of an ethyl ester derivative, obtained at pH 2 under Fischer esterification conditions, is described herein. Esterification blocked the supramolecular interactions typically observed through the carboxyl group of gabapentin, which resulted in a dramatic change in the solid-state structure. As it is known, this change could have a marked influence on the physiological absorption characteristics of the drug, which supports the search for ester-based gabapentin prodrugs as a means of improving the limited bioavailability of the drug. (C) 2010 Elsevier B.V. All rights reserved.