ORAL BIOAVAILABILITY ENHANCEMEMENT OF BROMOCRYPTINE MESYLATE BY SELF- MICRO EMULSIFYING DRUG DELIVERY SYSTEM (SMEDDS) Original Article DHARMANG PANDYA 1 *, BHAVIN RANA 1 , NILAY SOLANKI 1 1 Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science And Technology (CHARUSAT), Anand 388421, Gujarat, India Email: dharmangpandya1983@gmail.com Received: 06 Jan 2016 Revised and Accepted: 20 Apr 2016 ABSTRACT Objective: The purpose of this work was to enhance oral bioavailability of Bromocryptine Mesylate by preparing SMEDDS (self-micro emulsifying drug delivery system) Methods: Screening of oils, surfactants and co-surfactants were done by solubility study & pseudo ternary diagram. The batches of Bromocryptine Mesylate (BM)–SMEDDS were prepared and evaluated for droplet size analysis, poly dispensability index (PDI), robustness to dilution, zeta potential, in vitro dissolution. The optimized batch was compared with commercially available quick release tablets of BM (Brainstar®, 0.8 mg/tablet) by in vivo study (Pharmacodynamic study in rats). Results: Based on the drug’s solubility study, Akoline MCM, Tween80 and PEG400 were selected as oil, surfactant and co-surfactant, respectively. By pseudo ternary diagram, the components’ ratios were screened. In vitro drug release of the optimized batch was lower than the commercial preparation but in in vivo study, optimized batch was similar with commercial tablets. Conclusion: From the study, it was concluded that the group treated with optimized BM-SMEDDS showed better and sustained reduction in blood sugar as compared to control group and the group treated with marketed formulation, indicated improvement in bioavailability of drug. Keywords: Bromocryptine Mesylate, Type–II Diabetes, Self micro emulsifying drug delivery system, Bioavailability, Pharmacodynamic study © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Oral intake has been the most sought-after route of drug delivery by both patients and drug manufacturers for the treatment of most pathological states. Despite tremendous strides made in novel non- oral drug delivery systems, the majority of the drugs available commercially are oral formulations. Nevertheless, with oral delivery, over half of the drug compounds are diminished in the gastrointestinal tract because of their high lipophilicity and consequently poor aqueous solubility [1]. Oral bioavailability of such drugs, being primarily a function of their solubility and dissolution, [2] tends to exhibit inadequate magnitude with high intra-and inter- subject variability. Further, oral bioavailability also depends on upon a multitude of other drug factors such as stability in GI fluids, intestinal permeability, resistance to metabolism by cytochrome P450 family of enzymes present in gut enterocyte and liver hepatocytes and interactions with efflux transporter systems such as P-glycoprotein (P-gp) [3,4]. Type-II diabetes is a growing global pandemic that is estimated to af flict approximately 350 million people by the year 2030 [5]. This growing threat to human health requires medical interventions to lessen the morbidity associated with type-II diabetes. Type-II Diabetes is characterized by elevated fasting and postprandial plasma glucose concentrations which result from increased endogenous glucose production (EGP), decreased insulin-mediated muscle glucose disposal and suppression of endogenous glucose release and inadequate pancreatic insulin secretion. Obesity is a well-established risk factor for type-II diabetes. Extensive experimental evidence indicates that circadian neuroendocrine rhythms play a pivotal role in the development of seasonal changes in body fat stores and insulin sensitivity. Specifically, temporal changes in the interaction of 2 distinct neural circadian oscillations, mediated by dopaminergic and serotonergic neurotransmitter activity, have been shown to regulate the dramatic seasonal alterations in body weight and body composition that are characteristic of all vertebrate classes from teleost to mammals. Data obtained in rats, pigs, and humans suggest that similar mechanisms may play a role in the development of non-seasonal obesity and insulin resistance [6]. Bromocriptine mesylate (BM), an ergot derivative, is a sympatholytic dopamine D2 receptor agonist that exerts inhibitory effects on serotonin turnover in the central nervous system. It has been proposed that bromocriptine can reverse many of the metabolic alterations associated with obesity by resetting central (hypothalamic) circadian organization of monoamine neuronal activities. BM approved by USFDA for treatment Type-II Diabetes (Dec. 2008) is practically insoluble in water [7] and shows pH dependent solubility [8]. Only about 30% of an oral dose is absorbed from GIT bioavailability is only about 6% owing to extensive first-pass metabolism. Bromocriptine improves glycemic control and glucose tolerance in obese type-II diabetic patients. Both reductions in fasting and postprandial plasma glucose levels appear to contribute to the improvement in glucose tolerance. The bromocriptine induced improvement in glycemic control is associated with enhanced maximally stimulated insulin-mediated glucose disposal [6]. Self micro emulsifying drug delivery systems (SMEDDS)-isotropic mixtures of the drug, lipids (natural or synthetic oils), and emulsifiers (solid or liquid), usually with one or more hydrophilic co-solvents/co-emulsifiers are relatively newer, lipid-based technological innovations with immense promise in enhancing the oral bioavailability of drugs. [9, 10] These formulations have been shown to overcome the slow and incomplete dissolution of a drug, facilitate the formation of its solubilized phase, increase the extent of its transportation via the intestinal lymphatic system and bypass the P-gp efflux, thereby augmenting drug absorption from the GI tract [11]. This presents the opportunity to prepare the formulation in SMEDDS form to enhance dissolution with the bioavailability of poorly water soluble drug-BM for better treatment of diabetes. MATERIALS AND METHODS Materials Bromocriptine Mesylate (Helios Pharmaceuticals, Baddi, India), Etocas 35 HV-LQ (Croda Europe Ltd., Snaith Goole, United Kingdom), Tween 80 (Hi-Media, Vadodara, India), Captex 500 (Abitec International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 6, 2016