Development of extended release matrices of rifampicin using hot melt extrusion technique.

ABSTRACT

Tuberculosis has metamorphosized over the decades from drug resistant to multidrug resistant to the lethal extensively drug resistant forms lately. With scarce newer anti-TB drugs emerging, there is a pressing need to ameliorate the current treatment therapy by modulating the formulation approaches towards the first line treatment drugs. In the present study an attempt has been made to formulate Rifampicin (RIF), the first line treatment drug for TB as an extended release oral formulation using melt extrusion technique. The total dose of RIF was divided into two components- Immediate release (IR) pellets of RIF as the loading dose (300mg) and extended release tablet as the maintenance dose (150mg). Extrusion trials were conducted using various class of extrudable polymers (cellulose, polyvinyl acetate, polyethylene oxide, poly(meth)acrylates). Based on the preliminary findings, IR pellets were formulated using Eudragit EPO whereas hydroxylpropyl cellulose (HPC) was further explored as the matrix former. The release rate was modified using addition of hydrophilic pH independent release modifier. The formulation was characterized with respect to in vitro dissolution behavior, thermal and chemical stability, miscibility, drug-polymer interactions and surface morphology followed by stability studies. The loading dose could adequately release RIF initially whereas a combination of hydrophilic pH independent polymer of varying viscosity could successfully control RIF release over 24 hours following zero order release mechanism. The developed formulation exhibited content uniformity, physical and chemical stability over a period of six months. The application of melt extrusion for developing extended release matrices for anti-TB drugs like RIF was sought. Melt extrusion being a continuous manufacturing process could be scaled up commercially thus enhancing the feasibility of the designed formulation.