SOLUBILIZATION OF CELECOXIB USING ORGANIC COSOLVENT AND NONIONIC SURFACTANTS OPTIMIZED BY EXPERIMENTAL DESIGN
Objective: The solubility of drug substances in water is one of the major factors taken into account in the formulation of oral solutions and parenteral forms. The present study aims to evaluate the utility of a mixture design in improving water solubility of celecoxib through a micellar system by the use of organic co solvent and nonionic surfactants that are well tolerated by the parenteral route.
Methods: In our study, a design of experiments approach was tested using a mixture design of nonionic surfactants (TweenÂ® 80 and SolutolÂ®HS 15), an organic cosolvent (ethanol) and celecoxib. Solubility determination was based on the analysis of samples absorbance at 215 nm. A particles size measurement was conducted using a Dynamic Light Scattering at the point showing the maximum of solubility.
Results: The results showed a significant solubility increase in most of tested mixtures. The analysis of the design space showed that the solubility of celecoxib varies very closely with the concentration of TweenÂ® 80 associated with ethanol and SolutolÂ®HS 15 in water. Run 19 containing 0.8% of celecoxib, 10% of ethanol, 2% of TweenÂ® 80, 2% of SolutolÂ®HS 15 and water q. s. for 100% w/w improved celecoxib solubility by about 90 %, and showed an average particles size of 9.67 nm.
Conclusion: Micellar solubilisation associating a cosolvent and nonionic surfactants seems to improve celecoxib solubility significantly. Mixture design provides maximum information about the effects and the proportions of each component from a limited number of experiments.Keywords: Solubility, Celecoxib, Mixture design, Cosolvent, Surfactants
Lukyanov AN, Torchilin VP. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv Drug Delivery Rev 2004;56:1273-89.
MÃ¼ller RH, Keck CM. The second generation of drug nanocrystals for delivery of poorly soluble drugs: smartCrystal technology. Eur J Pharm Sci 2008;34(1, Suppl 1):20-1.
Jouyban A, Soltanpour S, Acree WE. The solubility of acetaminophen and ibuprofen in the mixtures of polyethylene glycol 200 or 400 with ethanol and water and the density of solute-free mixed solvents at 298.2 K. â€J Chem Eng Data 2010;55:5252-7.
MÃ¼ller BW, Albers E. Complexation of dihydropyridine derivatives with cyclodextrins and 2-hydroxypropyl-Î²-cyclodextrin in solution. Int J Pharm 1992;79:273-88.
Barenholz Y. Liposome application: problems and prospects. Curr Opin Colloid Interface Sci 2001;6:66-77.
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Delivery Rev 2000;45:89-121.
Balte AS, Goyal PK, Gejji SP. Theoretical studies on the encapsulation of Paracetamol in the Î±, Î² and Î³ cyclodextrins. J Chem Pharm Res 2012;4:2391-9.
Rupp C, Steckel H, MÃ¼ller BW. Solubilization of poorly water-soluble drugs by mixed micelles based on hydrogenated phosphatidylcholine. Int J Pharm 2010;395:272-80.
Seedher N, Bhatia S. Solubility enhancement of cox-2 inhibitors using various solvent systems. AAPS PharmSciTech 2003;4:33.
Mall S, Buckton G, Rawlins DA. Dissolution behavior of sulphonamides into sodium dodecyl sulfate micelles: a thermodynamic approach. J Pharm Sci 1996;85:75-8.
Rangel-Yagui CO, Pessoa AJ, Tavares LC. Micellar solubilization of drugs. J Pharm Pharm Sci 2005;8:147-63.
Samy AM, Ghorab MM, Shadeed SG, Mortagi YI. Effect of different additives on celecoxib release. Int J Pharm Pharm Sci 2013;5 Suppl 2:667-71.
Nagabhushanam MV, Prasada Rao CHV, Prabhakar CH. Hydrophilic polymers for dissolution enhancement of celecoxib. Int J Pharm Pharm Sci 2011;3 Suppl 5:547-9.
Lee JH, Kim MJ, Yoon H, Shim CR, Ko HA, Cho SA, et al. Enhanced dissolution rate of celecoxib using PVP and/or HPMC based solid dispersions prepared by spray drying method. J Pharm Invest 2013;43:205-13.
European Pharmacopoeia. 8th ed. France: EDQM; 2013. p. 1819-20.
Pravir C, Manavalan R, Rahul D, Girish J. Preformulation studies for the development of a generic capsule formulation of celecoxib comparable to the branded (Reference) product. Internet Printing Protocol 2013;1:230-43.
Jouzeau JY, Daouphars M, Benani A, Netter P. Pharmacology and classification of cyclooxygenase inhibitors. Gastroenterol Clin Biol 2004;28:7-17.
Huisman R, Van Kamp HV, Weyland JW, Doornbos DA, Bolhuis GK, Lerk CF. Development and optimization of pharmaceutical formulations using a simplex lattice design. Pharm Weekbl Sci Ed 1984;6:185-94.
De Boer JH, Smilde AK, Doornbos DA. The introduction of multi-criteria decision-making in optimization procedures for pharmaceutical formulations. Acta Pharm Technol 1988;34:140-3.
Eyraud M. Computer-aided experiment design for developing pharmaceutical forms. STP Pharma Prat 1992;2:345-51.
Gupta S, Kaisheva E. Development of a multidose formulation for a humanized monoclonal antibody using experimental design techniques. AAPS PharmSci 2003;5:1-9.
Martinello T, Kaneko TM, Velasco MV, Taqueda ME, Consiglieri VO. Optimization of poorly compactable drug tablets manufactured by direct compression using the mixture experimental design. Int J Pharm 2006;322:87-95.
Amalric N, Camara AL, Chanseaume L, Coiffard L, Cosson N, Degude C, et al. Cosmetic and nutritional complements stability studies. STP Pharma Prat 2007;17:3-14.
Rahali Y, Saulnier P, Benoit JP, Bensouda Y. Exploring ripening of nanocapsules and emulsions in parenteral nutritional mixtures by experimental design. J Drug Delivery Sci Technol 2013;23:255-60.
Mathieu D, Phan-Tan-Luu R. Planification dâ€™expÃ©riences en formulation: optimisation. Paris: Techniques de lâ€™ingÃ©nieur; 2001. p. 1-15.
Moulai Mostefa N, Hadj Sadok A, Sabri N, Hadji A. Determination of optimal cream formulation from long-term stability investigation using a surface response modeling. Int J Cosmet Sci 2006;28:211-8.
Rahali Y, PensÃ©-LhÃ©ritier AM, Mielcareck C, Bensouda Y. Optimization of preservatives in a topical formulation using experimental design. Int J Cosmet Sci 2009;31:451-60.
Rahali Y, Saulnier P, Benoit JP, Bensouda Y. Incorporating vegetal oils in parenteral nutrition using lipid nanocapsules. J Drug Delivery Sci Technol 2010;20:425-9.
El Alaoui Y, Sefrioui R, Bensouda Y, Rahali Y. Solubilization of acetaminophen using phospholipids and nonionic surfactants optimized by experimental design. J Chem Pharm Res 2014;6:39-46.
Rupp C, Steckel H, MÃ¼ller BW. Mixed micelle formation with phosphatidylcholines: the influence of surfactants with different molecule structures. Int J Pharm 2010;387:120-8.
Rowe R, Sheskey P, Quinn M. Handbook of pharmaceutical excipients. 6th ed. UK: Pharmaceutical Press; 2009. p. 917.
Liste des Excipients Ã Effet Notoire: Mise Ã Jour de la liste et des libellÃ©s selon le Guideline europÃ©en 2003. France: AFSSAPS; 2009. Available from: http://ansm.sante.fr/var/ ansm_site/ storage/original/application/29aa941a3e557fb62cbe45ab09dce305.pdf. [Last accessed on 23 Nov 2015].
Bakshi MS, Singh J, Kaur G. Fluorescence study of solubilization of l-Î±-dilauroylphosphatidyl ethanolamine in the mixed micelles with monomeric and dimeric cationic surfactants. J Photochem Photobiol A 2005;173:202-10.
Bakshi MS, Singh J, Kaur G. Mixed micelles of monomeric and dimeric cationic surfactants with phospholipids: effect of hydrophobic interactions. Chem Phys Lipids 2005;138:81-92.
Bakshi MS, Singh K, J Singh. Characterization of mixed micelles of cationic twin tail surfactants with phospholipids using fluorescence spectroscopy. J Colloid Interface Sci 2006; 297: 284-91.
Hammad MA, MÃ¼ller BW. Increasing drug solubility by means of bile salt-phosphatidylcholine-based mixed micelles. Eur J Pharm Biopharm 1998;46:361-7.
Hammad MA, MÃ¼ller BW. Solubility and stability of tetrazepam in mixed micelles. Eur J Pharm Sci 1998;7:49-55.
Sznitowska M, Klunder M, Placzek M. Paclitaxel solubility in aqueous dispersions and mixed micellar solutions of lecithin. Chem Pharm Bull 2008;56:70-4.
Lichtenberg D, Robson RJ, Dennis EA. Solubilization of phospholipids by detergents structural and kinetic aspects. Biochim Biophys Acta 1983;737:285-304.
Kaushik P, Vaidya S, Ahmad T, Ganguli AK. Optimizing the hydrodynamic radii and polydispersity of reverse micelles in the triton X-100/water/cyclohexane system using dynamic light scattering and other studies. Colloids Surf A 2007;293:162-6.
Wei Z, Hao J, Yuan S, Li Y, Juan W, Sha X, et al. Paclitaxel-loaded pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization. Int J Pharm 2009;376:176-85.
Su QJ, Mo T, Liu L, Pan HC, Deng B, Liu H. Paclitaxel-loaded KolliphorÂ® HS15/Polysorbate 80-mixed nano micelles: formulation, in vitro characterization and safety evaluation. Lat Am J Pharm 2015;34:702-11.
Strickley RG. Solubilizing excipients in oral and injectable formulations. Pharm Res 2004;21:201-30.
Rong Liu. Editor. Water-Insoluble Drug Formulation. 2nd ed. Florida: Tylor and Francis group; 2008. p. 119.