Research paper Solubility enhancement of celecoxib using b-cyclodextrin inclusion complexes Swati Rawat a, * , Sanjay K. Jain b a YB Chavan College of Pharmacy, Rouza Bagh, Aurangabad, MS, India b Department of Pharmaceutical Sciences, Dr Harisingh Gour Vishwavidyalaya, Sagar, MP, India Received 26 May 2003; accepted in revised form 29 October 2003 Abstract Celecoxib has very low water solubility. It forms a complex with b-cyclodextrin (bCD) both in aqueous and in solid state. It was observed that due to formation of the inclusion complex, the solubility and dissolution rate of celecoxib were enhanced. The formation of 1:1 complex with bCD in solution was confirmed by phase solubility and spectral shift studies. The apparent stability constants calculated by these techniques were 881.5 and 341.5 M 21 , respectively. The solid inclusion complexes of celecoxib and bCD were prepared by the kneading method using different molar proportions of bCD, and formation of solid inclusion complexes of celecoxib and bCD at different molar ratios were confirmed by differential scanning calorimetry. Enhancement of dissolution rates with increasing quantity of bCD in the complex was observed. It was also observed that the complexes exhibit higher dissolution rates than the pure drug and physical mixture. q 2003 Elsevier B.V. All rights reserved. Keywords: Cyclooxygenase-2 inhibitors; Cyclodextrin; Inclusion complex; Phase solubility 1. Introduction Enzymatic hydrolysis of starch usually results in formation of glucose, maltose and a long range of linear and branched dextrins. However, a number of different microorganisms and plants produce certain enzymes called cyclodextrin glucosyltransferases (CGTs), which degrade starch to cyclic products called cyclodextrins. These are cyclic oligosaccharides consisting of a lipophilic central cavity and a hydrophilic outer surface. Because of such characteristics, cyclodextrins form inclusion complexes both in solution and in solid state, in which each guest molecule is surrounded by the hydrophobic environment of the cyclodextrin cavity. This can lead to alteration of the physical, chemical and biological properties of the guest molecules and can eventually have considerable pharma- ceutical potential [1]. Out of the three parent cyclodextrins, b-cyclodextrin (bCD) appears most useful as a pharma- ceutical complexing agent because of its complexing ability, low cost and other properties. There are two types of complex cyclodextrin forms with the guest molecules, type A (L) that forms in solutions and type B (S) which forms in solid complex [2]. Apart from the kneading [3], the solid drug can be complexed with bCD by freeze drying [4], spray drying [5], co-evaporation [6] or by roll mixing [7]. Therefore, bCD was selected to form an inclusion complex with celecoxib to enhance its solubility. Celecoxib, 4-[5-(4-methyl phenyl)-3-(triflouromethyl)- 1H-pyrazol-1-yl], is a non-steroidal anti-inflammatory drug (NSAID), which is a specific cyclooxygenase-2 (COX-2) inhibitor [8] for pain and inflammation. Celecoxib offers the unique therapeutic prospect of alternative pain and inflam- mation without untoward gastric tract, renal and platelet effects associated with conventional NSAIDs. Because, celecoxib is a COX-2-specific inhibiting agent it inhibits the conversion of arachidonic acid to the prostaglandins that mediate pain and inflammation, while having no effect on the formation of the prostaglandins that mediate normal homeostasis in the GI tract, kidney and platelets and that are formed under the control of cyclooxygenase-1 [9]. It is also used in the treatment of orthopedics, familial adenoma- tous polyps [10] and in dental practice [11]. It has comparable efficacy and superior gastric tolerability [12] and it is safer, when compared to the conventional NSAIDs [13]. The major 0939-6411/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2003.10.020 European Journal of Pharmaceutics and Biopharmaceutics 57 (2004) 263–267 www.elsevier.com/locate/ejpb * Corresponding author. YB Chavan College of Pharmacy, Rouza Bagh, Aurangabad, MS 431001, India. Tel.: 00919422206357; fax: 00912402380077. E-mail address: swati@k.st (S. Rawat).