Development of novel budesonide pellets based on CODES[TM] technology: In vitro/in vivo evaluation in induced colitis in rats

Budesonide is the drug of choice for treatment of active inflammatory bowel disease [IBD]. The aim of this study was to develop budesonide pellets based on a novel colon drug delivery system [CODES]. Pellet cores containing lactulose or mannitol were prepared by extrusion/spheronization and coated with an acid soluble polymer [Eudragit E100], hydroxypropylmethyl cellulose [HPMC] and an enteric coat [Eudragit FS 30D] sequentially. In vitro drug release of coated pellets was studied using USP dissolution apparatus type II in buffers of pH 1.2 [2 hrs], pH of 7.4 [4 hrs] and pH of 6.8 containing 8% rat cecal contents [RCC] [18 hrs]. The efficacy of the optimized formulation [containing 50% lactulose coated with Eudragit E [30% w/w] and Eudragit FS 30D [12% w/w]] was evaluated against 2, 4, 6-trinitrobenzenesulfonic acid [TNBS]-induced colitis in rats. The results of the kind of bacteria in vitro dissolution tests indicated absence of drug release in pHs of 1.2 and 7.4 and controlled release in buffer of pH 6.8 containing RCC. It was found that release rate was controlled by the type and amount of polysaccharide and the thickness of the acid soluble layer. The prepared formulation showed promising results in alleviating the conditions of experimental model of colitis. The results of this study suggest that pellets based on CODES technology could be useful for colonic delivery of budesonide

Pharmacokinetic study of niosome-loaded insulin in diabetic rats

Encapsulation of human insulin in lipid vesicular systems such as niosomes was sought as a route to protect this protein against proteolytic enzymes and to improve its oral bioavailability The purpose of this study was to assess the effect of insulin encapsulation in niosomes on oral bioavailability in diabetic rats. Recombinant human insulin was entrapped in multilamellar niosomes composed of polyoxyethylene alkyl ether surfactants [Brij 52 and Brij 92] or sorbitan monostearate [Span 60] and cholesterol. The amount of insulin released in simulated intestinal fluid [SIF] and simulated gastric fluid [SGF] were measured at 37°C. The protection of entrapped insulin against pepsin, a-chymotrypsin and trypsin were evaluated in comparison with free insulin solution. Diabetes was induced by IP injection of streptozotocin [65 mg/kg] in male wistar rats and effects of orally administered niosomes and subcutaneously injected insulin on hypoglycemia and elevation of insulin levels in serum were compared. The extent and rate of insulin release from Brij 92 and Span 60 vesicles were lower than that of Brij 52 niosomes [P<0.05]. Vesicles protected insulin in comparison with free insulin solution against proteolytic enzymes [P<0.05] significantly Animals treated with oral niosome-encapsulated insulin [100 lU/kg] showed decreased levels of blood glucose and elevated serum insulin, which in the case of Brij 92 niosomes, hypoglycemic effect was significant [P<0.05]. Niosomes were also stable in solubilizing bile salt solutions and could effectively prolong the release of insulin in both SGF and SIF. Results of this study showed that niosomes may be utilized as oral carriers of insulin; however, to increase bioavailability of insulin, further studies on the protease inhibitor co-encapsulation in niosomal formulations might be helpful

[Formulation of insulin containing niosomes and the effect of their oral administration on blood glucose in streptozotocin-induced diabetic rats]

Multilamellar vesicles [noisome] of polyoxyethylene alkyl ether surfactants [Brij 52, 72, 76 and 92] were prepared using classic film hydration method. Vesicle formation ability of the surfactants was assessed in presence or absence of cholesterol. All used surfactants formed vesicles in the absence of cholesterol. Recombinant human insulin was used as a model protein drug to investigate encapsulation efficiency and release characteristics of the vesicles. The amount of insulin released in simulated intestinal fluid [SIF] and simulated gastric fluid [SGF] from Brij 92 vesicles was lower than the other ones. These vesicles also showed the highest protection of insulin against proteolytic enzymes, pepsin and trypsin. Diabetes was induced by IP injection of streptozotocin [65 mg/kg] in male wistar rats. Animals treated with oral niosome [Brij 52 and 92]-encapsulated insulin [100 IU/kg] showed decreased levels of blood glucose and elevation of serum insulin, which in the case of Brij 92 niosomes the hypoglycemic effect was significant [P< 0. 05]