Journal of Pharmaceutical Research & Clinical Practice, Oct-Dec 2016; 6(4):8-16 ISSN: 2231-4237 Avinash R Tekade et.al, JPRCP 2016; 6(4) 8 Research Article Preparation of Nanoparticles of Poorly Water Soluble Dronedarone by Antisolvent Addition Technique using Natural Polymer as a Stabilizer B. D. Yeole, R. P. Patil, K. D. Lone, A. R. Tekade* Department of Pharmaceutics, JSPM’s Rajarshi Shahu College of Pharmacy and Research, Tathawade, Pune- 411033, Maharashtra, India. ABSTARCT The aim of this study was to enhance the solubility, dissolution rate and bioavailability of poorly water soluble drug Dronedarone (DRO) by preparing nanoparticles with antisolvent precipitation process. In this Caesalpinia pulcherrima gum (CPG) was used as a stabilizer. The influence of operation parameter such as solvent to antisolvent ratio, stirring speed, stabilizer concentration was experimentally investigated. The results indicated that increasing solvent to antisolvent ratio, stirring speed, stabilizer concentration affected the particle size. The prepared nanoparticles of DRO were characterized by scanning electron microscopy (SEM), Fourier transform Infrared(FT-IR) spectroscopy, differential scanning calorimetry (DSC), X- ray diffraction(XRD), in vitro drug release and in vivo study in suitable animal model. The SEM image exhibited some aggregation of individual nanoparticles, FT-IR analysis confirmed that molecular structure of nanoparticles of DRO and observed no change after precipitation. The DSC and XRD indicate that crystallinity of DRO nanoparticles which was lower than the pure drug. The dissolution of DRO nanoparticles in pH 4.5 phosphate buffer was faster than pure drug in 15 min. These nanoparticles showed dramatically increase oral bioavailability in wistar rat. Nanoparticles of dronedarone prepared by antisolvent precipitation technique proved to be effective in improving oral bioavailability as a result of enhanced solubility and dissolution rate. Keywords: Dronedarone, Caselpinia pulcherima gum, nanoparticles, antisolvent precipitation. Received 19 Oct 2016 Received in revised form 5 Dec 2016 Accepted 22 Dec 2016 *Address for correspondence Dr. Avinash R. Tekade, Department of Pharmaceutics, JSPM’s Rajarshi Shahu College of Pharmacy & Research, Tathawade, Pune-411033, Maharashtra, India. E-mail: avitekade@gmail.com, rahulpatil16793@gmail.com INTRODUCTION It has been reported that approximately 40 % of drug in industry pipeline fall in the Biopharmaceutics Class II (low solubility high permeability) and Class IV (low solubility low permeability) category [1]. Generally, these poorly soluble drug are plagued with low and highly variable bioavailability due to it dissolution rate limited performance [2]. Therefore, it is important for such kind of drugs to enhance their dissolution rate and improve its bioavailability. Various approaches commonly used to improve dissolution and bioavailability of poorly water soluble drug such as reducing particle size to increase surface area, by coating drug particle with hydrophilic surfactant [3, 4]. Formation of solid dispersion and crystalline to amorphous state with regard to the Noyes – Whiteny and Ostwald- Freundlich equations, size reduction can offer increased dissolution and solubility characteristic [5-7]. In solid dispersion systems are theoretically one of the appropriate methods for increasing dissolution rate, but molecules in the amorphous state are not thermodynamically stable; they can convert to the crystal form during storage [8]. Many approaches have been used for reduction in particle size including micronization, supercritical fluid technique antisolvent precipitation [9-11]. Micronized powders with a higher energetic surface show poor flow property [12]. Supercritical fluid technique is believed to be attractive method for the size reduction, providing particles with narrow size distribution. However, it’s required complex operating condition and also they have the limitations of low yield and high equipment cost hence difficult to control and scale up [13]. Antisolvent precipitation process is promising technique to prepare ultrafine drug particle [14, 15]. The basic principle is that the drug dissolved in solvent; the solvent solution is