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

[Preparation of diltiazem topical gel for the treatment of anal fissure and in-vitro, ex-vivo drug release evaluations]

Anal fissures are small tears in the lining skin of the anus presenting with typical symptoms of pain and bleeding during defecation. Several new forms of medicines such as glyceryle trinitrate [GTN] ointments and diltiazem, a calcium channel-blocking agent, have been recently used for the treatment of these fissures. Diltiazem relaxes the muscle of anal sphincter and consequently increases blood flow to promote healing. It does not have GTN side effects like headache, anal burning and hypotension. The objective of this study was to formulate a suitable topical gel from diltiazem and then to investigate its physicochemical stability and also the drug release profiles from the bases. Various formulations of gel base including Guar 1.25%, Tragacanth 1.5%, HPMC 1%, and HPMC 1.5% were prepared and in vitro release and penetration characteristics of diltiazem from each preparation were studied through a hydrophilic dora pore diffusion barrier and membrane excised rat skin using Franz cell over a period of 5 hours. The amount of drug released from topical preparations was determined spectrophotometrically a lambda[max]=236 nm. Stability studies and shelf life assessments were performed too. Gel formulations containing HPMC, Guar and Tragacanth presented both good chemical and physical stabilities. The rates of cumulative drug release from HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases using synthetic membrane were 89.7%, 76.7%, 94.9% and 66.1% respectively. For excised rat skin test, the cumulative percent of penetrated drug at the end of each experiment were 52.7%, 50.9%, 64.6% and 42.6% for HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases respectively. The comparative study showed that the percent of drug release from synthetic membrane was more than the percent of penetrated drug through excised rat skin for all bases [P<0.05]. It was concluded that the kinetics of diltiazem release in vitro was not affected by the kind of gel forming agent and for all of the formulations, Higuchi's kinetic model was suitable to explain their kinetics

[Clinical evaluation of a topical doxepin cream [5%] in treatment of eczema]

Eczema is one of the most common pruritic skin disorders for which various treatments are used to relieve the symptoms. There are several reports about the efficacy and in part safety of topical doxepin in the treatment of pruritic dermal diseases. However, lack of a suitable topical preparation from this drug in our country persuaded us to design the present trial. A randomized, double blind, placebo controlled and multi- central clinical trial was carried out in Isfahan during the years of 1383-84 by using 60 volunteers and both the drug and placebo were given QID for 8 days. The efficacy, side effects and their relevance to sex and age of subjects were assessed before, during and after the treatment. The data were analyzed using non-parametric tests including Mann-Whitney, Wilcoxon, and Kendall Tau where appropriate. Results indicated that doxepin cream effectively reduced disease symptoms including pruritus [75.5%], inflammation [43.8%] skin dryness [37.5%] exudates [59.5%], lichenification [41.5%], and eczema [41.5%] after the course of treatment [the day of 8]. Same results were obtained by using placebo. Stinging as an adverse effect was occurred in both the drug [30%] and placebo [27%] groups. Although there was no significant difference between the two groups, it can be concluded that doxepin cream [5%] is effective in depressing the signs and symptoms of pruritic skin disorders. A larger clinical trial is needed to evaluate the efficacy and safety of the product more precisely