Formulation and Evaluation of Transdetmal Patches of Boswellic Acids and Guggul Sterones for the Treatment of Rheumatoid Arthritis

Abstract

Traditional herbal medicines have great potential, but due to poor understanding of the formulation aspect and bioavailability of the herbal medicines, these medicines are consider into the complementary and alternative medicines (CAM). Various alternative therapies have been used to treat the diseases like diabetes, asthama, arthritis etc. Rheumatic diseases have affected mankind since ages and are one of the commonest inflammatory conditions in developing countries like India and China. Rheumatoid arthritis (RA) forms a major prototype of rheumatic diseases and it is a common cause of disability. Boswellic acids and guggulsterones both are very well pharmacologically proved phytoconstituents for the treatment of rheumatoid arthritis. Boswellic acids a natural mixture isolated from oleo gum resin of Boswellia serrata comprised of four major pentacyclic triterpene acids: β-boswellic acid (the most abundant), 3-acteyl-β-boswellic acid, 11-keto-β-boswellic acid, and 3-acetyl-11-keto-β-boswellic acid, is reported to be effective as anti-inflammatory, immunomodulatory, antitumor, anti-asthmatic and in chronic colitis disorders. It inhibits pro-inflammatory mediators in the body, specifically leukotrienes via inhibition of 5-lipoxygenase, the key enzyme of leukotriene synthesis, is the scientifically proved mechanism for its anti-inflammatory/anti-arthritic activity. Guggulsterone [4,17(20)-pregnadiene-3,16-dione] is a plant derived steroid isolated from the gum resin of the Commiphora mukul tree, termed guggulipid, extensively used in the Ayurvedic medicine to treat conditions associated with inflammation such as hyperlipidemia, obesity, and arthritis. In this present study we have isolated total boswellic acids and guggulsterones from Boswellia serrata and Commiphora mukul respectively, which are very well pharmacologically proved for the treatment of rheumatoid arthritis. Identification of those isolated phytoconstituents was also done by thin layer chromatography.Initial optimization and evaluations were conducted for the transdermal films and formulation of transdermal films were done by polymer hydroxyl propyl methyl cellulose (HPMC) 15cps (2.5 %), plasticizer polyethelene glycol 400 (PEG400) (30 %) and solvent methanol. Physical evaluations (e.g. tensile strength, thickness, folding endurance and % elongation) were also carried out for these formulations. For the isolated fraction of the total boswellic acids and guggulsterones the transdermal films were formulated with optimized polymer and plasticizer concentrations and different batches of films were evaluated for their physical parameters. For estimation of the total boswellic acids from the formulations, we have developed in-house colorimetric method. Calibration curve of total boswellic acids was taken in chloroform using Liebermann-Burchard reagent (cold acetic anhydride + Conc. Sulphuric acid ) and linearity was observed between 10μg/ml to 500μg/ml with R square value of 0.998. For in-vitro release studies the transdermal systems were administered to the Franz diffusion cells. Diffusion of boswellic acids from the formulations through the membrane (dialysis bag) was also studied using diffusion cells. The results were found satisfactory. After 10 hrs % drug release were found 46.57%, 77.83% and 79.27% of the batches B1, B2 and B3 respectively. For ex-vivo studies, we have used rat skin and human cadaver skin. The % drug release after 10 hrs in ex-vivo studies in rat skin was found to be 48.36% and 75.97 % in human cadaver skin. Boswellic acids transdermal films were further carried out for the in-vivo drug release using male wistar rats. The Cmax was found 125.667 μg/ml in 3 hrs. Transdermal film formulations of pharmacologically active phytoconstituents like boswellic acids and guggulsterones could be useful to cure arthritis and inflammation effectively in human.