Dissolution enhancement by bio-inspired mesocrystals: the study of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate.

PURPOSE

The aim of this paper is to enhance the dissolution rate of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate via a bio-inspired method of growing mesocrystals.

MATERIALS AND METHODS

Mesocrystals of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate were successfully prepared from a supersaturated aqueous solution of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate having the initial degree of supersaturation, S ( 0 ), of 1.326 and the initial saturated concentration, C*, of 0.986 mol/l at 25 degrees C with sodium dodecyl sulfate (SDS) at a concentration of 0.10 g/l. Dynamic light scattering, scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and optical microscopy with cross polarizers were employed to understand the formation mechanism and to characterize the superstructures of the SDS generated mesocrystals.

RESULTS

The SDS generated mesocrystals were the assembly of the oriented attachment of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate nano-sized platelets under the mediation of the side-to-side interaction between SDS and racemic (R,S)-(+/-)-sodium ibuprofen dihydrate. The SDS generated mesocrystals contained a mixture of the racemic compounds in alpha- and beta-forms and the resolved racemic conglomerate in gamma-form with no detectable amount of SDS. The dissolution rate of the SDS generated mesocrystals was more rapid than the one of its counterpart made by conventional crystallization pathway.

CONCLUSIONS

The crystallization of racemic (R,S)-(+/-)-sodium ibuprofen dihydrate in the presence of SDS yielded well-faceted, well-separated, but almost perfectly three-dimensionally aligned nano-sized platelets. This kind of bio-inspired mesocrystal superstructure has definitely opened a new doorway for crystal engineering and pre-formulation design in pharmaceutical industry. The future work is to study the mesocrystal formation of some other active pharmaceutical ingredients in organic solvent systems and to develop an efficient method for screening the additives.