Formulation and Evaluation of Raloxifene Hydrochloride Co-Crystals with Bioenhancer – a Potential Approach for Solubility and Bioavailability Enhancement

Purpose

The main purpose of the research work was to formulate cocrystals of Raloxifene Hydrochloride(RXL-HCl) in order to increase its solubility and oral bioavailability. The effect of addition of bioenhancer on the oral bioavailability was also examined.

Methods

Co-crystals of RXL HCl with tartaric acid as a coformer were successfully formulated with salt to coformer stoichiometric ratio of 1:1 by using solvent evaporation method. Characterization was done by FTIR analysis, SEM, DSC, pXRD, solubility, in- vitro dissolution, and in-vivo pharmacokinetic study.

Results

Optical microscopy and SEM analysis revealed the formation of plate-shaped crystals. The stretching and bending vibration patterns were different in the FTIR spectra of the developed formulation in comparison to the RXL HCl indicating the formation of the co-crystals. DSC analysis showed a melting endotherm at 235ºC which is less than that of RXL HCl indicating the formation of co-crystals. The pXRD pattern of co-crystals was different compared to that of the RXL HCl. The solubility of co-crystals in aqueous media was found to be 14.1 mg/mL which is almost 80 folds higher compared to RXL HCl. The in-vitro dissolution study of co-crystals showed 82.9%, 57%, and 65% drug dissolution after 120 min in water, acidic media, and alkaline media respectively, which is significantly greater compared to the RXL HCl. The in-vivo pharmacokinetic study showed almost 6 folds higher bioavailability compared to the marketed product.

Conclusion

Administration of cocrystals of Raloxifene Hydrochloride with Naringin as a bioenhancer led to a significant enhancement in oral bioavailability.