Gastroretentive delivery of rifampicin: In vitro mucoadhesion and in vivo gamma scintigraphy

Rifampicin, a first line anti-tubercular drug, has maximum solubility and permeability in the stomach. An oral multi-particulate formulation with site specific sustained delivery of rifampicin was developed. This oral gastroretentive rifampicin formulation consisted of rifampicin pellets for immediate release as the loading dose and a bio/mucoadhesive rifampicin tablet for extended release. Immediate release pellets of rifampicin were prepared by extrusion-spheronization process and were evaluated for physico-mechanical properties: usable yield, size, shape, abrasion resistance, mechanical crushing force, residual moisture and drug release. For the mucoadhesive rifampicin formulation, statistical experimental strategy was utilized to simultaneously optimize the effect of two independent variables namely amount of Carbopol and MCC. The two dependent responses selected were, work of adhesion: estimated using Texture Analyzer and T-50%; determined from dissolution studies. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastroretentive formulation, the in vivo gamma scintigraphy was carried out in six healthy human volunteers, after radiolabeling the formulation with Tc-99m. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 320 min. The human data validates the design concept and signifies the potential of the developed system for stomach targeted delivery of rifampicin for improved bioavailability. (C) 2011 Elsevier B.V. All rights reserved.