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

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 b-cyclodextrins was investigated. Matrix tablets of albendazole-b-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 67.771.9% of albendazole in the presence of rat caecal contents, whereas in the control study the formulation released only 29.770.2% of albendazole. A significant difference (Po0.001) 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 401C/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.

A novel dissolution method for evaluation of polysaccharide based colon specific delivery systems: A suitable alternative to animal sacrifice

“…The methods that have been reported for evaluation of colon targeted delivery systems include triggering by enzymes (Philip et al, 2008;Fetzner et al, 2004;Macfarlane et al, 1989;Maculotti et al, 2009;Maestrelli et al, 2008;Liu et al, 2012;Semde et al, 2000a,b Omar et al, 2007Jain et al, 2007a,b et al, 2010), rat caecal contents (Rubinstein et al, 1993;Jain et al, 2007a,b;Watanabe et al, 1998;Takemura et al, 2000;Tiwari et al, 2011;Shukla et al, 2012Shukla et al, , 2011Krishnaiah et al, 2001;Shyale et al, 2005;Ravi et al, 2008;Varshosaz et al, 2010;Singhal et al, 2011;Wei et al, 2007;Seal and Mathers, 2001), human faecal slurries (Salunkhe and Kulkarni, 2008;Siew et al, 2000Siew et al, , 2004McConnel et al, 2007;Karrout et al, 2009;Krenzlin et al, 2011), and multi stage compound culture system (Yang, 2008;Kotla et al, 2014;Schacht et al, 1996). Despite a large number of research reports on microbially triggered delivery systems for colon delivery, no such product is commercially available.…”

Preparation and in vitro/in vivo evaluation of dextran matrix tablets of budesonide in experimental ulcerative colitis in rats

“…It is clear from these results that MT7 and MT10 formulations could target budesonide to the colon and may be considered as potential formulations for targeting of budesonide to the colon, especially because human caecal contents would be greater than that used in the present study (Shyale et al, 2005). MT10500 which was selected for in vivo studies showed a significant decrease in macroscopic and histological damage scores and colon wet weight/length ratio.…”

Microencapsulation of budesonide with dextran by spray drying technique for colon-targeted delivery: anin vitro/in vivoevaluation in induced colitis in rat

“…Shyale et al (2005) have also reported in their studies on guar gum, that 7-day enzyme induction was suitable for preparing rat caecal contents with enough concentration of the required enzymes. The rats were then sacrificed by decapitation and after midline incision; luminal contents of caecum and colon were removed and transferred to appropriate buffer solutions containing 0.5% sodium lauryl sulphate (SLS) to preserve the sink condition for budesonide.…”