Role of additives like polymers and surfactants in the crystallization of mebendazole

Abstract

Crystallization in the presence of additives like surfactants and polymers is a relatively less explored area but is important for polymorphic screening of a compound during its developmental stage. Surfactants and polymers act by various mechanisms to influence either the growth or the nucleation phase, resulting in modification of either the polymorphic form or the crystal habit. The present study was aimed at understanding the crystallization behavior of the model drug mebendazole (MBZ) in the presence of an inert polymer polyvinyl pyrrolidone (PVP) and an anionic surfactant sodium lauryl sulphate (SLS). Crystals were generated by the antisolvent approach using the surfactant and polymer solutions in water as the antisolvents. Change in habit from needles to plates took place as a result of modification of the crystallization process in the presence of additive molecules. This was confirmed by quantification of these additives using specific analytical methods, which revealed their presence in small amounts in the final product (0.02, 0.15, and 0.24- w/w SLS in crystals generated using 0.5, 1.0, and 2.0- SLS, respectively, and 0.94, and 1.24- w/w PVP K30 and PVP K90, respectively). Their presence in the crystals led to modification in the dissolution of the drug. SLS improved the extent of dissolution while PVP had a negative impact and led to reduction in the amount of MBZ released even below that of the pure drug. The study highlights the influence of polymeric and surfactant additives on the crystallization process leading to modified performance. © 2008 The Pharmaceutical Society of Japan.