Gelatin microspheres of rifampicin cross-linked with sucrose using thermal gelation method for the treatment of tuberculosis

Abstract

Oral controlled release microspheres of rifampicin (RIF) were prepared in order to circumvent the required regular high dose of the conventional dosage forms for the treatment of tuberculosis. Rifampicin containing microspheres were designed by using a biodegradable and biocompatible polymer, gelatin B, using a thermal gelation method. The microspheres were cross-linked with natural cross-linker, sucrose, to avoid the toxicities due to the synthetic di- and poly-aldehydes. This formulation was found to be controlled release for drug in the gastro-intestinal tract. Drug encapsulation efficiency was found to be in the range of 52–83%. These microspheres were characterized for; particle size analysis by optical microscopy and scanning electron microscopy; in vitro release study by USP paddle apparatus and drug polymer interaction study using DSC and FT-IR. The results suggested that microspheres prepared by the above method were smaller in size, i.e. less than 60 µm and sucrose could be used as an interesting means to cross-link gelatin B microspheres, allowing the use of this formulation for controlled release of rifampicin. Microspheres could be observed in the intestinal lumen at 4 h and were detectable in the intestine 24 h post-oral administration, although the percentage of radioactivity had significantly decreased (t_1/2 of ^99mTc = 4–5 h). Dissolution and scintigraphy studies have shown promising results, proving the utility of the formulation for the whole intestine.

• Sugar
• rifampicin
• cross-linked
• thermal gelation method
• DSC
• FT-IR