Glyceryl monooleate functionalized matrix with an inter polyelectrolyte complex system for the management of drug resistance in tuberculosis

Abstract

ObjectiveInter polyelectrolyte complexes (IPECs) are an emerging biocompatible polymeric carrier system to transport active substances at target sites. The aim of this study was to evaluate the use of hydrophobic waxy retardant polymer glyceryl monooleate in hydrophilic inter polyelectrolyte matrix system containing three principal anti-tubercular drugs (ATDs). Sustained release polymeric matrix system was prepared by melt granulation technique, which allowed for the manufacture of the multi-layered tablets for segregated delivery of rifampicin, isoniazid and pyrazinamide.The matrix system consisting of hydrophilic IPEC of chitosan and carboxymethyl guar gum in combination with hydrophobic waxy retardant polymer, prepared by melt granulation technique was found to achieve segregated delivery of rifampicin, isoniazid and pyrazinamide. The applicability of piperine, an organic alkaloid as bio enhancer and rifampicin-sodium lauryl sulphate (SLS) complex was tested for improvement in bioavailability of antituberculosis fixed dose combination (FDC), lowering dosage levels and shortening the treatment course.ResultsThere was no incompatability observed between drug and excipeints based upon FTIR, DSC and X-RD studies. The optimized tablet (composition IPEC 46 % w/w (275mg), glyceryl monooleate 2 % w/w (11.5mg), piperine 1 % w/w (5 mg), pyrazinamide (150mg), isoniazid (50mg) and rifampicin-SLS complex (95.2mg) sustained the delivery of drugs for 12 h. IPECs alone lack sufficient mucoadhesion hence, suitable combination of polymeric blends along with IPEC played a key role in controlling the initial burst release pattern, desired bioadhesion (14.25g) and swelling index (1248.8%).This biocompatible, biodegradable and naturally renewable polymeric matrix system could be successfully utilized in a FDC to maximally release ATDs in a sustained manner achieving complete dissolution.