In-vitro, Ex-vivo Skin Permeation and Biological Evaluation of 18-β- Glycyrrhitic Acid Transdermal Patches

Objective: Transdermal patch is a promising approach that allows continuous input of drugs with short biological half-lives. 18 β-Glycyrrhitic acid (GA) is chemically pentacyclic triterpenoid which possess powerful antiinflammatory action. The present study was designed to formulate GA reservoir-type transdermal patches using piperine as bioenhancer. Method: Transdermal Patch of GA was prepared using heat seal technique using 2*3 factorial design allowing for independent variables like penetration enhancers, formulation matrix and rate controlling membranes. The GA patches were evaluated for in-vitro and ex-vivo drug permeation through cellophane membrane and rat skin respectively. The biological evaluation regarding skin irritation study and the anti-inflammatory effect of GA patches on rat paw edema were tested and compared with standard Aceclofenac patch. Result: The reservoir-type patch of F4 formulation, containing 5% menthol as a permeation enhancer, 42% ethanol, 2% carbopol 934 gel bases (50 g) with 0.5% piperine provided an improved sustained release of phytopharmaceuticals through transdermal administration. The anti-inflammatory action F4 formulation showed no skin irritation with significant inhibition of rat paw edema compared with standard patch. Conclusion: The GA patch was demonstrated the feasibility for future biopharmaceutical study in clinical trials. INDRODUCTION: GA is a pentacyclic triterpenoid derivative of the beta-amyrin type obtained from the hydrolysis of glycyrrhizic acid, which was obtained from the herb liquorice.The structure of GA is similar to that of cortisone. Both molecules are flat and similar at position 3 and 11. This might be the basis for licorice's antiinflammatory action. It is solid off-white powder, molecular formula C30H46O4, melting point 292 0c, molar mass 470.68 g mol −1 , soluble in ethanol and chloroform 1, 2 . 100μM GA suppresses LPSinduced TNF-α production and NF-κβ activation in mouse macrophages. QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.IJP.2(8).400-408 Article can be accessed online on: www.ijpjournal.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.2(8).400-08 The results showed that treatment with 20–75 μM GA inhibit the production of LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2) and intracellular reactive oxygen species (ROS) 3 . The liposomal gel with GA 0.9% showed a stronger anti-inflammatory activity than triamcinolone acetonide and econazole nitrate cream 4 . The oral LD (50) in rats was reported to be 610 mg/kg. Higher LD (50) values were generally reported for salts 5 . Piperine is a pungent alkaloid present in Piper nigrum Linn, was reported to have antidiarrhoeal, anti-inflammatory, immuneenhancing, anticonvulsant and antioxidant activity. Piperine may work as a drug bioavailability enhancer, which is evident by the increase in the Cmax and AUC of phenytoin, propranolol, and theophylline by co administration of piperine (20 mg/kg) 6 . Transcutaneous permeation of Repaglinide (antidiabetic drug) in rats was enhanced by 8-fold eywords: Reservoir-Type Transdermal Patch, GA, Piperine, Carbopol 934, Skin Irritation Test, Inhibition of Edema Correspondence to Author: