PREPARATION AND EVALUATION OF IGURATIMOD ORAL FORMULATION USING CYCLODEXTRIN NANOSPONGES

Abstract

Objective: Cyclodextrin nanosponges have unfolded themselves as budding delivery aids for intractable molecules that face difficulty in formulation. Methods: The present research aimed at the preparation of cyclodextrin-based nanosponges employing diphenyl carbonate crosslinker as reported elsewhere. Box-Behnken design was adopted to evaluate the effects of factors (reaction temperature, reaction time and stirring speed) on practical yield and particle size. Based on a numerical optimization technique, five batches of nanosponge formulations with varying molar ratios (1:2, 1:4, 1:6, 1:8 and 1:10) were formulated and evaluated. Results: The drug loading into optimized β–CD (NS14, NS16) was carried out by by freeze-drying method with a maximum drug loading of 32% displayed by IGNS14. The particle sizes of Iguratimod-loaded nanosponges range between 178 to 181 nm with lower polydispersity indices. The formulation IGNS14 and IGNS16 displayed optimal zetapotential of-27 and-26 mV, which is sufficient to stabilize the colloidal nanosuspension. The dissolution of both nanosponges was significantly higher (>98%) and controlled when compared to pure drug (34%). Retention of the drug in the optimized nanosponges was observed, which was released slowly over time. The PXRD confirm the formation of paracrystalline nanosponges that are spherical in shape with no interaction amongst the drug and excipients. Conclusion: The cyclodextrin-based NS of Iguratimod were a probable alternative for drug delivery with improved physicochemical properties and therapeutic efficacy.