Development of curcumin containing direct compressible gastro-retentive tablets

Abstract

Curcumin is the main active compound found in turmeric that exhibits many medicinal actions such as anti-inflammatory, anti-oxidative, antimicrobial and anti-cancer effects. However, the systemic delivery of curcumin by means of oral administration is severely limited due to its poor water solubility, instability in neutral and alkaline environments as encountered in certain regions of the gastrointestinal tract and susceptibility to first pass metabolism. The aim of this study was to circumvent these challenges by a formulation approach where functional excipients were incorporated with curcumin in a modified solid oral dosage form namely a gastro-retentive mini-tablet-in-capsule system. The capsule formulation contained both conventional immediate-release mini-tablets (to provide the loading dose) and floating matrix type gastro-retentive mini-tablets (to provide the maintenance dose). A floating matrix type gastro-retentive delivery system prolongs the residence time of the dosage form in the acidic stomach environment where curcumin is expected to be more stable. Incorporation of functional excipients (e.g. hydroxypropyl-β-cyclodextrin) increased its solubility thereby potentially also its bioavailability, while the sustained release formulation was intended to maintain blood plasma levels over an extended period of time. The suitable filler materials and quantities thereof required for the production of the gastro-retentive tablets was determined by using the SeDeM expert diagram system. The solubility of curcumin was noticeably enhanced by forming an inclusion complex with hydroxypropyl-β-cyclodextrin. The efficacy of the formulation approach in terms of curcumin delivery was evaluated across synthetic cellulose nitrate membrane filters in a Sweetana-Grass diffusion apparatus. This study has shown that the preparation of an inclusion complex of curcumin with hydroxypropyl-β-cyclodextrin markedly increased the solubility of curcumin (30 000-fold). Although the mini-tablet-in-capsule dosage forms showed promise with increased membrane transport of the prepared complex formulations compared to curcumin formulations, overall curcumin delivery was not on an acceptable level. Additional research would therefore be required to further increase the bioavailability of curcumin such as by incorporating drug absorption enhancers in the dosage form.