37 Zaltoprofen- â-CD Inclusion Complex for Solubility Enhancement Vivekanand K. Chatap*, Abhishek R. Maurya, Gajanan M. Marathe, Nandkishor D. Patil Post Graduate Department of Pharmaceutics & Quality Assurance, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India-425405 *Correspondence: chatap@rediffmail.com; Tel.:+91-9373848788 Abstract The aim of present work was to investigate the inclusion complexation of zaltoprofen (ZPF), a water insoluble drug, with â-cyclodextrin (â-CD) in order to improve solubility and dissolution rate of the drug in an attempt to enhance its bioavailability. The complex of ZPF/ â-CD (1:1) was characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Fourier-transform infrared (FT-IR) spectroscopy, solubility and dissolution studies. According to the DSC/PXRD data, no endothermic and characteristic diffraction peaks corresponding to ZPF were observed for the inclusion complex, suggesting that, crystallinity of zaltoprofen was reduced. FTIR study revealed that there was no drug- polymer interaction between ZPF and â-CD. The complex ZPF/â-CD (1:1) exhibited higher dissolution rate than that of pure drug and physical mixture in both pH6.8 and pH7.4 buffer solutions. The aqueous solubility of the complex increased to about 150 and 145 folds in pH6.8 and pH7.4 buffer, respectively with that of pure ZPF. In conclusion, complexation method proved to be the better alternative for the solubility enhancement of poorly water soluble drugs. Keywords: Zaltoprofen, â-cyclodextrin, solubility, dissolution rate, inclusion complex Introduction Zaltoprofen is a propionic acid derivative of non-steroidal anti- inflammatory drugs (NSAIDs). Chemically, it is 2-(10-oxo-10, 11- 1 dihydrodibenzo [b, f] thiepin-2-yl) propionic acid, (Fig. 1) an important group of NSAIDs and which has powerful inhibitory effects on acute and chronic inflammation with less adverse 2-3 reactions on the gastrointestinal tract than other NSAIDs. As zaltoprofen has a unique action to inhibit bradykinin (BK) induced 3-4 nociception. S C H 3 COOH O Fig. 1: Chemical structure of ZPF ZPF exerts anti-inflammatory actions and analgesic effects by inhibiting prostaglandin synthesis and through a peripheral mechanism by inhibition of bradykinin B2 receptor-mediated 5-6 7 bradykinin responses in primary afferent neurons. Bawolak et al. found that ZPF potently suppressed the relaxant response recruited by the kinin, which implied that ZPF was more potent than ibuprofen in this respect. ZPF was already used in the treatment of rheumatoid arthritis and osteoarthritis as well as to relieve inflammation and pain after surgery, injury and tooth extraction. 8 Recently, a double-blind study conducted in 170 patients indicated that the effect and safety of ZPF as a single dose to reduce inflammation in acute upper respiratory tract infection was also excellent, which provided a scientific evidence on the proper use of ZPF in the therapy of acute respiratory infections. Cyclodextrins are crystalline, cyclic oligosaccharides with a bucket-like structure having a hydrophobic internal cavity and a hydrophilic exterior cavity that allows the configuration of inclusion complexes, in which lipophilic compounds are non- covalently bound within the cavity. Cyclodextrin have been employed in the pharmaceutical industry to increase the aqueous solubility and stability of drugs and that have been used in both 9 parenteral and oral drug delivery systems. Jadhav et al., prepared 10 oral controlled porosity osmotic pump tablet of zaltoprofen. Various approaches to improve drug solubility, complexation with cyclodextrin are widely used. It was reported in 2010 that zaltoprofen was formulated into tablet to enhance the bioavailability and to achieve sustained-release using additives such as lactose monohydrate, carboxymethylcellulose and 11 hydroxypropylmethylcellulose. Cyclodextrin are powerful carriers for improving the therapeutic efficacy of drugs by means of Journal of PharmaSciTech ISSN: 2231 3788 (Print) ISSN: 2321 4376 (Online) Research Article http://www.pharmascitech.in Volume 3 (Issue 1) 2013; Journal of PharmaSciTech