Formulation development and in-vitro/in-vivo correlation for a novel Sterculia gum-based oral colon-targeted drug delivery system of azathioprine.

ABSTRACT

The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6 h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T(max), prolonged absorption time, decreased C(max) and absorption rate constant (Ka) indicating reduced systemic toxicity of the drug as compared to other dosage forms.