Journal of Pharmacy Research Vol.5 Issue 2.February 2012 R. R. Thenge . / Journal of Pharmacy Research 2012,5(2),974-977 974-977 Research Article ISSN: 0974-6943 Available online through http://jprsolutions.info * Corresponding author. R. R. Thenge Department of Pharmaceutics, IBSS College of Pharmacy, Malkapur-443101, Maharashtra, India. I NTRODUCTI ON Crystal Modification of Aceclofenac by Spherical Crystallization to Improve Solubility Dissolution Rate and Micromeritic Properties R. R. Thenge* Department of Pharmaceutics, IBSS College of Pharmacy, Malkapur-443101, Maharashtra, India Received on:10-11-2011; Revised on: 15-12-2011; Accepted on:12-01-2012 ABSTRACT Aceclofenac a non-steroidal anti-inflammatory drug widely used in the treatment of rheumatoid arthritis. The poor water solubility and poor micromeritic properties of aceclofenac lead to low dissolution rate and poor flow during tableting. The aim of present study was to improve dissolution rate and micromeritic properties of aceclofenac by spherical agglomeration techniques. The spherical agglomerate of aceclofenac was carried out by solvent change method in the presence of hydrophilic polymer in different concentration. The solvent system used was acetone, water and dichloromethane as good solvent, anti-solvent and bridging liquid respectively. The spherical agglomerates were characterized by FTIR spectroscopy, scanning electron micros- copy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. Also the agglomerates were evaluated for dissolution rate and micromeritic properties. The FTIR and DSC study showed no interaction between drug and polymer. XRD studies showed a slight decrease in crystallinity in agglomerates. The agglomerate showed significantly improved dissolution rate as well as micromeritic properties compared to pure drug. The SEM also showed that the agglomerate possess a good spherical shape. Key words: Aceclofenac, spherical agglomerate, solubility, dissolution, micromeritic properties Spherical crystallization is the novel agglomeration technique that can di- rectly transform the fine crystals produced in the crystallization or in the reaction process into a spherical shape 1 . It is the versatile process that enables to control the type and the size of the crystals. It is the particle engineering technique by which crystallization and agglomeration can be carried out simultaneously in one step to transform crystals directly into a compacted spherical form 2, 3 . This technique of particle designing of drugs has emerged as one of the areas of active research currently of interest in pharmaceutical manufacturing and came into the forefront of interest or gained great attention and importance due to the fact that crystal habit (form, surface, size, and particle size distribution) can be modified during the crystallization process. As a consequence of such modifications in the crystal habit, certain micrometric properties (bulk density, flow property, and compactibility) and physicochemical properties (solubility, dissolu- tion rate, bioavailability, and stability) can also be modified 4 . It had been described as a very effective technique in improving the dissolution behav- ior of some drugs that are characterized by low water solubility and a slow dissolution profile by using hydrophilic polymer during crystallization process 5,6 . It has also been applied to improve the flowability and the compression ability of some powders. Moreover, critical steps involved in wet granulation can be avoided. Aceclofenac, a non-steroidal anti-inflamma- tory drug (NSAID), is the selective cyclooxygenase-2 inhibitor used in the treatment of osteoarthritis and rheumatoid arthritis in adult patients. Aceclofenac exhibits poor flow and compression characteristics and is hence a suitable candidate for spherical crystallization process to improve the flow properties and compressibility. Also, aceclofenac shows incomplete and poor oral bioavailability due to low aqueous solubility 7, 8 . Hence, the improvement of aqueous solubility in such a case is a valuable goal to improve therapeutic efficacy. Spherical crystallization of aceclofenac was prepared in the presence of hydrophilic polymer polyvinyl pyrrolidone to improve the aqueous solubility, dissolution rate and micromeritic proper- ties, compare with pure drug. Materials and Method Aceclofenac was a gift sample from Lupin pharmaceuticals Pvt ltd. Pune. PVP K-30 was purchased from S. D. Fine chemicals, Mumbai. All other chemicals and solvents used were of analytical reagent grade. Spherical crystallization The spherical agglomeration was carried out using solvent change method. The clear solution of aceclofenac (3.0 g) in acetone (20 ml) was added quickly to a 100 ml solution hydrophilic polymer (PVP-K30) in water at different concentration (2.5- 10.0 w/v). The mixture was stirred continu- ously at 500 rpm by using a mechanical stirrer. After 15 Min. fine crystals begun to precipitate then dichloromethane (bridging liquid) was added dropwise to obtain spherical agglomerates. The agglomerates were collected by filtration using Whatman filter paper and dried for 24 h at room tempera- ture and store in desiccator. Micromeritic properties 9 Angle of Repose: Angle of repose was determined using Fix funnel method. The spherical agglomerates were poured through a funnel that can be raised vertically until a maximum cone height (h) was obtained. Radius of the heap (r) was measured and angle of repose (?) was calculated using the following formula, θ= Tan -1 (h / r) Where, θ= angle of repose, r = radius of the pile, h = height of the pile Bulk Density: Bulk density (B) was determined by pouring the spherical agglomerates into a graduated cylinder. The bulk volume (V) and weight of the powder (M) was determined. The bulk density (B) was calculated using following formula, B= M / V Where, M= weight of the powder, V= bulk volume Tapped Density: The measuring cylinder containing a known mass of spheri