Vol 12, Issue 4, 2019 Online - 2455-3891 Print - 0974-2441 BIOAVAILABILITY AND DISSOLUTION ENHANCEMENT OF GLYBURIDE NANOSUSPENSION PRADEEP KUMAR M*, CHANDRA SEKHAR KB Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Ananthapuram, Andhra Pradesh, India. Email: pradeepbadvel98@gmail.com Received: 22 January 2019, Revised and Accepted: 19 February 2019 ABSTRACT Objective: The main objective was to develop nanosuspension of glyburide (GLY) by quasi emulsification solvent diffusion method and to enhance dissolution and bioavailability characteristics of the drug GLY, an antidiabetic drug which belongs to Biopharmaceutical Classification System-II category. Results: From these studies, it was confirmed that drugs and excipients chosen were compatible with each other. GLY-8 was the best formulation with a particle size of 85–96 nm with 168.7°C melting point, freely soluble in phosphate buffer pH 7.4, 93.53% drug entrapment, and 90.26±1 mV of zeta potential. This formulation shows percentage drug release of 99.85% in 24 h. In vivo pharmacokinetic study for optimized formulation (GLY -8) suggested that there was no reaction with the rat plasma. From the results, it was shown that C max and T max were found to be 0.604±0.03 μg/ml and 2±1.01 h, respectively. The values of t 1/2 (h), area under the curve (AUC) (0-t) , and AUC (0-∞) were found to be 10.04 h, 2.562±0.41 μg.h/ml, and 2.147±0.45 μg.h/ml, respectively. Conclusion: Based on the results obtained, oral administration of nanosuspension could not only provide the better absorption of poorly water soluble drugs but may also reduce toxicity and provide a new tool in drug delivery system. Keywords: Glyburide, Scanning electron microscopy studies, In vitro drug release, In vivo pharmacokinetic evaluation, Dissolution and bioavailability enhancement. INTRODUCTION In the drug discovery and development, poor water solubility is regarded as wide problem. More than 40% of drugs are poorly soluble in water, so they show problems in formulating them in conventional dosage forms. This problem is complex for Class II drugs which are poorly soluble in aqueous and organic media. Nanosuspension preparation is preferred for compounds that are insoluble in water (but are soluble in oil) with high log p value. Various approaches are there to resolve problems of low solubility and low bioavailability such as micronization, cosolvency, oily solution, and salt formation, and some other techniques are liposomes, emulsions, microemulsion, solid dispersion, and β-cyclodextrins inclusion complex. In these cases, nanosuspensions are preferred. It is most suitable for the compounds with high log p value, high melting point, and high dose. Nanosuspensions can be used to enhance the solubility of drugs that are poorly soluble in aqueous as well as lipid media. As a result, the rate of flooding of the active compound increases and the maximum plasma level is reached faster (e.g., oral or intravenous administration of the nanosuspension). This is one of the unique advantages that it has over other approaches for enhancing solubility. It is useful for molecules with poor solubility, poor permeability, or both, which poses a significant challenge for the formulators [1]. Glibenclamide which is also known as glyburide (GLY) belongs to second-generation sulfonylurea. It is majorly used to treat non- insulin-dependent diabetes mellitus and administered orally [2]. GLY has been classified as the Biopharmaceutical Classification System (BCS) class-II drug due to its low aqueous solubility, with bioavailability of 100% and huge permeability. The solubility of GLY in gastrointestinal fluids and pH in the gastrointestinal tract impact on its in vivo dissolution. A lot of approaches have been made to optimize in vivo dissolution and bioavailability. However, to predict the in vivo performance of a dosage form, it is necessary to have an in vitro–in vivo correlation studies. The main objective of this study was to develop nanosuspension of GLY by quasi emulsification solvent diffusion method and also to enhance dissolution and bioavailability. This manuscript includes 12 formulations of GLY which were prepared with three different polymers such as polyvinyl alcohol (PVA), hydroxypropyl methyl cellulose (HPMC), and Eduragit (EDG) with a stabilizer, i.e. poloxamer 407 with formulation codes from GLY-1 to GLY-12. The best formulation had been identified and further subjected to both in vitro and in vivo studies [3-5]. The present study brought out the best formulation with an enhanced dissolution and bioavailability. MATERIALS AND METHODS Materials GLY drug sample was procured from Hetero Drugs, Hyderabad. HPMC was procured from Yucca Enterprises, Mumbai. PVA was brought from Yarrow Chem Products., Mumbai. EDG RL 100 was procured from Yucca Enterprises, Mumbai. Poloxamer 407 was procured from SD Fine Chem, Hyderabad. All other chemicals and reagents utilized in the study were with the analytical grade. Analytical method development Determination of λ max Ultraviolet (UV) spectrum of GLY was carried out in phosphate buffer pH 7.4. 10 mg of GLY was weighed accurately and transferred to a 10 ml © 2019 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/) DOI: http://dx.doi.org/10.22159/ajpcr.2019.v12i4.31657 Research Article Methods: In this work, nanoparticles were prepared using polyvinyl alcohol, hydroxypropyl methyl cellulose, and Eudragit RL100. Twelve formulations of GLY (GLY-1–GLY-12) were formulated using the excipients at various compositions. Drug and excipient compatibility studies were conducted using Fourier transform infrared and differential scanning calorimeter. The prepared nanosuspension was analyzed using scanning electron microscopy for surface of the particle analysis, melting point, solubility, particle charge zeta (mv), percentage drug entrapment efficiency (%), and in vitro drug release. The optimized formulations of nanosuspension were further studied for in vivo pharmacokinetic evaluation. Reverse-phase high-performance liquid chromatography method was developed, validated, and used for the study of these formulations in rat plasma.