Development of colon‐targeted albendazole‐β‐cyclodextrin‐complex drug delivery systems

Abstract

Abstract Albendazole, a drug for the treatment of gastrointestinal nematode infection, is variably and erratically absorbed from the gastrointestinal tract after oral administration. The present study was aimed at developing matrix tablets of albendazole using guar gum as carrier for colon targeting in order to provide an effective and safe therapy for helminthiasis. To improve its bioavailability, the formation of inclusion complexes of albendazole with β‐cyclodextrins was investigated. Matrix tablets of albendazole–β‐cyclodextrin complex were prepared by the wet granulation method using guar gum as matrix carrier in various proportions: 20% (SAC‐20), 30% (SAC‐30), and 40% (SAC‐40). A high‐performance liquid chromatography–ultraviolet method was developed to quantitate albendazole using mebendazole as internal standard at 254 nm. The granules were compressed using 12‐mm round, flat, and plain punches. Tablets were evaluated for various physical characteristics such as thickness, hardness, and drug content uniformity. The matrix tablets were subjected to in vitro drug release studies in 0.1 N HCl (2 h), pH 7.4 Sorensen's phosphate buffer (3 h) and simulated colonic fluids. The SAC‐30 released 67.7±1.9% of albendazole in the presence of rat caecal contents, whereas in the control study the formulation released only 29.7±0.2% of albendazole. A significant difference ( P <0.001) was observed at 24 h in the amount of albendazole released from SAC‐30 when compared to the dissolution study without rat caecal contents. The study shows that the release of albendazole in the physiological environment of colon is due to the microbial degradation of guar gum compression‐coated tablets in the presence of rat caecal contents. Stability studies were carried out at 40°C/75% relative humidity for 6 months to assess their long‐term (2 years) stability. No change either in their physical appearance or in drug content was observed. Drug Dev. Res. 65:76–83, 2005. © 2005 Wiley‐Liss, Inc.