Simvastatin

The present study was aimed at developing Simvastatin loaded transdermal patch to prevent drawbacks associated with oral delivery of Simvastatin. Simvastatin is a BCS class II drug having poor aqueous solubility and good permeability. A transdermal patch of simvastatin was developed using various polymers and their combination like Eudragit RL 100, HPMC K4M, PVP K30 & Ethyl Cellulose. Polymer combination HPMC K4M & PVP K30 exhibited good film forming properties. Propylene glycol, oleic acid and glycerol were used as plasticizers to improve film-forming properties. Among these, propylene glycol exhibited excellent result but penetration was found to be less. Thus, penetration enhancers such as oleic acid, DMSO, PEG 200 were used to enhance permeability, of which DMSO was found to be excellent. A 22 factorial design was implemented using design expert software. The formulation was optimized on basis of 2 parameters percent cumulative release and percent drug content.  3D surface graph was plotted for the design. Grid survey indicated P1 batch (which contains HPMC K4M & PVP K30 as a polymer, DMSO as penetration enhancer & PEG as a plasticizer) is the optimized batch as it showed good drug content and in-vitro drug release. The drug release kinetics of transdermal patch of simvastatin was best expressed by Higuchi model of drug release.

Ulcerative colitis is a chronic-relapsing, progressive inflammatory bowel disease characterized by diffuse mucosal inflammation of the colon. Repeated damage and injury of the intestinal surface are key features of inflammatory bowel disease. It can be concluded that sitagliptin is partially effective for treatment of experimentally induced ulcerative colitis model in mice. Furthermore, it can be also concluded that effects of simvastatin treatment were mostly dose dependantfor treatment of experimentally induced ulcerative colitis model in mice. Thus, the aim of this study is to evaluate effect of combination of sitagliptin and simvastatin as an early treatment of experimentally induced ulcerative colitis in mice. Furthermore in this study, effect of large dose of either sitagliptin or simvastatin will be compared with combination of both drugs. Thirty mice were equally divided into the following groups: control group, non-treated DSS-induced colitis group, DSS-induced colitis mice treated with simvastatin(50mg/kg/d)group, DSS-induced colitis mice treated with sitagliptin (100 mg/kg/day) group, DSS-induced colitis mice treated with sitagliptin (20mg/kg/d) combined with simvastatin (5mg/kg/d) group. Combination of sitagliptin 20 mg/kg/d + simvastatin 5 mg/kg/d produced a significant decrease in serum TNF-α, colonic tissue MDA & NO levels.Furthermore, reduced glutathione was significantly increased up to near normal level. As regard colon length, it returned to nearly normal length. Combination of small dose of both drugs showed 66% decrease in DAI. This combination restored normal histological appearance of the colon. This is a very good combination as regards to their small doses and consequently less adverse effects.