Solvent-Mediated Nonoriented Self-Aggregation Transformation: A Case Study of Gabapentin

A good powder performance is one of the essential targets for gabapentin (GBP). However, the low bulk density and flowability of GBP are still the industrial problems in practical production. The main purpose of this paper is to investigate the phase transformation of GBP from form I to form II in methanol, ethanol, propanol, acetone, acetonitrile, and ethyl acetate and improve the powder properties. The results suggested that there are two kinds of phase transformation mechanisms of GBP. One is the classic solvent mediated transformation in alcohols, and the other is the solvent-mediated nonoriented self-aggregation transformation in other solvents, which is proposed for the first time. On account of the low water activity and solubility, there is a self-cleaving phenomenon caused by the dehydration in the form I particles, and then the unstable phase transforms into form II, but the growth of the stable form is confined by the size and shape of the initial metastable particle and the products are aggregates. These aggregates with a well-defined shape and size have good performance in the dissolution rate with improved bioavailability.