Perfil Comparativo De Diferentes Técnicas Para Mejorar La Solubilidad Del Valdecoxib

www.ijpsonline.com

Research Paper

A Comparative Solubility Enhancement Profile of Valdecoxib with Different Solubilization Approaches
A. MODI 1 AND P. TAYADE*
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai - 400 098, India, 1 H. K. College of Pharmacy, Pratiksha Nagar, Jogeshwari (W), Mumbai - 400 102, India.

formulation process. Buffers,cosolvency, surfactants and complexation are most commonly encountered pharmaceutical techniques for solubilizing drug(s) with low aqueous solubility2. Micellar solubilization i.e, using surfactant is one of the oldest and robust techniques of solubilization. With advent of nonionic surfactant, with low critical micellar concentration, compatibility with biological system and high solubilizing power, hasbeen gaining importance in recent times. These surfactants, in aqueous environment, aggregate themselves to form micelles that can be defined as two-region system, inner nonpolar
*For correspondence E-mail: pralhadtayade@yahoo.com
274 274 CMYK

m ro f d ns oa tio nl a ow blic d e Pu ). fre w m r fo kno .co e w bl ed no ila y M dk va substancee region of hydrocarbon part and exterior capsularregion Aqueous solubility of any therapeutically activeb a is a key property as it governs dissolution, absorption.and inner hydrophobic core s may d definedm of polyoxyethylene chains. Thecalled mantle are usually i s thus the efficacy in vivo. Solubilization te be w as and extended interfacial region w the preparation of a thermodynamically stable solution of the locus of solubilization fornonpolar drugs . F D ho w a substance that is normally insoluble or(very slightly P of soluble in a given solvent, by e introduction of one or s sit theSolubilization of poorly Natural as well as hydrophilic derivativestheir natural more amphiphilic i cyclodextrins are being in great focus for role as hcomponent(s) . aqueous soluble drug forms an important activity in solubilizing excipient.Cyclodextrins (CD) are cyclic T a
Solubility enhancement of poorly aqueous soluble drug is an important aspect of formulation development. Although there is plethora of reports of solubility improvement using different techniques, a comparative study of different solubilization approaches are few. Valdecoxib chemically designated as 4-(5-methyl-3-phenyl-4-isoxazolyl) benzenesulfonamide is a novel potentCOX-2 inhibitor having poor aqueous solubility (10 µg/ml). Since it is poorly water-soluble, various techniques could be applied to increase its aqueous solubility. Objective of present study was to provide a comparison of effect of various solubilization techniques, namely micellar solubilization, cyclodextrin complexation and cosolvency, on solubility of valdecoxib. Solubility of valdecoxib wasdetermined in various ionic and nonionic surfactants using phase solubility analysis. Similar type of study was performed using different water:cosolvent mixture. In addition, solubility improvement by use of 2 novel hydrophilic β-cyclodextrin derivatives, hydroxypropyl β-cyclodextrin and sulfobutyl ether-7-β-cyclodextrin was examined. Results showed that highest solubility (70 fold) was achievedwith use of Cremophor EL followed by Tween 80 and sulfobutyl ether-7-β-cyclodextrin. It was found that surfactants with higher HLB values were better solubilizers. Solubilization capacity was found to increase with increase in hydrocarbon chain of surfactant, suggesting hydrocarbon core of micelles as locus of solubilization. Similarly, less polar solvents were found to increase solubility bygreater extent, thus accentuating hydrophobic interaction mechanism. Among cyclodextrin, higher binding constant and solubility enhancement was obtained by use of sulfobutyl ether-7-β-cyclodextrin. Thus, the study generated an important dataset so as to compare effect of various solubilizers on solubility of valdecoxib.
3 1

oligosaccharide (α 1 → 4 linked) of α-D-glucopyranose. The most important...