Original Article EFFECT OF WATER CONTENT IN KNEADING METHOD OF SOLID DISPERSION TECHNIQUE FOR SOLUBILITY ENHANCEMENT SHANKARGURU P., RAMYA DEVI D, VEDHA HARI B. N. * Department of Pharmaceutical Technology, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, Tamil Nadu, India Email: vedhahari@scbt.sastra.edu Received: 15 Feb 2017, Revised and Accepted: 22 Aug 2017 ABSTRACT Objective: The main objective of the research work was to optimize the water requirement/content used in kneading method for solid dispersion/inclusion complex formation between water insoluble drug and polymer. Methods: Nimesulide (model drug) and β-cyclodextrin were taken in a different ratio such as 1:1, 1:3 and 1:5 and, the mixture was triturated well for half hour. Water was incorporated to the mixture in different levels like 75%, 50%, 25% w/v in divided proportions and 0% (no water addition, but the mixture was triturated continuously). After each part of water addition, the mixture was triturated well for 10 min and dried using hot air over for 30 min at 50 °C and sieved using sieve no: 44. The complexes formed were subjected for various analytical characterization studies including solubility, particle size, the angle of repose, tapped density, Carr’s index, fourier transform infrared spectrometry (FTIR), thermo gravimetric-differential thermal analysis (TG-TDA), x-ray diffraction (XRD) studies and in vitro dissolution studies. Results: The dissolution studies showed improvement in the release of nimesulide, which depended on the percentage level of water. The solubility of the sample was increased with increasing the concentration of the inclusion complex formed. Kneading method was proved to be a successful technique for formation of stable inclusion complex of nimesulide with β-cyclodextrin. All the formulations exhibited acceptable particle size and solubility in the range of 22.6±2 to 29±5 and 45±5 to 133±3.5 respectively. Conclusion: Nimesulide and β-cyclodextrin complex was successfully prepared and characterized for the drug-polymer stability and interactions. The result confirmed that the liquid content in the solid dispersion prepared by the kneading method played an important role in the dissolution of the poorly soluble drug. Keywords: Nimesulide, β-cyclodextrin, Solid dispersion, Kneading method © 2017 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/ijap.2017v9i5.17765 INTRODUCTION Nimesulide (NM) is one of the potent non-steroidal anti- inflammatory drugs (NSAIDs), widely prescribed for various anti- inflammatory conditions. NM has categorized under class II drugs of the biopharmaceutical classification system (BCS) that illustrate poor aqueous solubility, which is the main reason for its low and variable oral bio availability [1-3]. NM is an acidic drug that differs from many similar compounds, by virtue of the presence of sulfoanilide group rather than a carboxyl group. Chemically it is named as [4-nitro-2-(phenoxy) methane sulphoanilide] (fig. 1). Fig. 1: Structure of nimesulide [2] Pharmacologically NM is an inhibitor of cyclo-oxygenase-2 (COX-2) enzyme, and hence inhibits the synthesis of critical prostaglandins and spares cytoprotective prostaglandins. It can also inhibit the process involved in platelets aggregation [4-6]. The oral absorption of NM is dissolution rate limited, and hence enhancement in solubility and dissolution rate is required for increasing its oral bioavailability [7]. Among different methods reported for improving the solubilization of NM, the formation of an inclusion complex with cyclodextrins (CDs) (fig. 2) has been identified as the most common and successful approach. CDs exhibit a hydrophilic outer surface and lipophilic inner cavity with a cyclic torus shape, which is capable of interacting with a large variety of guest molecules to form an inclusion complex. CDs are commonly used in drug formulations as solubility enhancers because of their ability to form water soluble complexes with poorly water soluble drugs. They also have huge potential as carrier molecules in the formulation of novel drug delivery systems. The inclusion complexes can modify pharmacokinetic properties of guest molecules by fitting within the hydrophobic cavity of CDs [8, 9]. Several NSAIDs have been complexed with CDs, which resulted in high solubility and dissolution rate, decreased side effects, reduced dose, improved bioavailability and stability, lesser gastric irritation and also enhanced the palatability of the active molecules [10-13]. Fig. 2: Structure of β-cyclodextrin [12] Kneading is one of the common methods used in solid dispersion technique for the enhancement of solubility and dissolution rate of International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 9, Issue 5, 2017