EFFECT OF A BINARY BLEND COMPOSED OF POLOXAMER AND PVP ON AQUEOUS SOLUBILITY OF GRISEOFULVIN
Keywords:
Solid dispersion, Griseofulvin solubility, OptimizationAbstract
Objective: The aim of this study was to improve the aqueous solubility of a poorly water soluble drug griseofulvin.
Methods: To accomplish this goal a technique of solid dispersion with polyvinyl pyrolidone (k30) and poloxamer 407 was used. Solubility of griseofulvin alone and the solid dispersion were performed in 10 ml purified water and measured spectrophotometricaly atλ max 295 nm to detect the coefficient of improvement.
Results: Solubility of griseofulvin alone was found to be 0.812 mg and the solubility of solid dispersion ranged from1.64 to 9.56 mg. After generating polynomial models correlating the variables using a D-Optimal mixture design, an optimal formulation with desired response was proposed by the statistical package. For validation, a new solid dispersion formulation based on the optimized composition was prepared and tested for solubility of griseofulvin. The optimized solid dispersion formulation enhances the solubility of griseofulvin by about 12 folds. Increase the amount of poloxamer in the optimized formulation increases the griseofulvin solubility to about 6 folds more than the optimized form.
Conclusion: solid dispersion technique in conjunction with statistical design was shown to be very efficient for the optimization and improvement of aqueous solubility of poorly soluble drugs.
Â
Downloads
References
Berge MS, Bighley DL, Monkhouse SD. Pharmaceutical salts. J Pharm Sci 1977;66:1-19.
Kaneniwa N, Ikekawa A, Hashimoto K. Influence of operational variables on ball-milling of sulfadimethoxine and white alundum. Chem Pharm Bull 1973;21:676–81.
Yamamoto K, Nakano M, Takaichi A, Nakai Y. Dissolution rate and bioavailability of griseofulvin from a ground mixture with microcrystalline cellulose. Eur J Pharm Biopharm 1974;2:487–93.
Kimura K, Hirayama F, Arima H, Uekama K. Effect of aging on crystallization, dissolution and adsorption characteristics of amorphous tolbutamide-2-hydroxypropyl-cyclodextrin complex. Chem Pharm Bull 20004;8:646–50.
Sekiguchi K, Obi N. Studies on absorption of eutectic mixture. I. A comparison of the behavior of eutectic mixture of sulfathiazole and that of ordinary sulfatiazole in man. Chem Pharm Bull 1961;9:866–72.
Barka A, Pathak YV, Benita S. Polyacrylate (Eudragit retard) microspheres for oral controlled release of nifidipine. I Formulation design and process optimization. Drug Dev Ind Pharm 1990;16:2057-75.
Benita S, Barkai A, Pathak YV. Effect of drug loading extent on the in vitro release kinetic behavior of nifidipine from polyacrylate microspheres. J Control Release 1990;12:213.
Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm 2002;54:107-17.
Breitenbach J, lewis J. Two concept, one technology: controlled release and solid dispersion with meltrex. In: Rathbone MJ, Hadgraft J, Roberts MS, editors. Modified release drug delivery technology. New York: Marcel Dekker; 2003. p. 125-34.
Brabander CD, Mooter GVD, Vervaet C, Remon JP. Characterization of ibuprofen as a nontraditional plasticizer of ethyl cellulose. J Pharm Sci 2002;91:1678-85.
Takahashi H, Chen R, Okamoto H, Danjo K. Acetaminophen particle design using chitosan and a spray-drying technique. Chem Pharm Bull 2005;53:37-41.
Weuts I, Kempen D, Verreck G, Decorte A, Peeters J, Brewster M, et al. Study of the physicochemical properties and stability of solid dispersions of loperamide and PEG6000 prepared by spray drying. Eur J Pharm Biopharm 2005;59:119-26.
Chauhan B, Shimpi S, Paradkar A. Preparation and evaluation of glibenclamidepolyglycolized glycerides solid dispersion with silicon dioxide by spray drying technique. Eur J Pharm Sci 2005;26:219-30.
Serajuddin ATM. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci 1999;88:1058–91.
Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 2007;12:1068–75.
Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000;50:47–60.
Generic Drug Formulations. http://www. anhuipharm. com.cn/ upload/2008-4/20084837083077
Abdul Rasool A, Hussain AA, Dittert L. Solubility enhancement of some water-insoluble drugs in the presence of nicotinamide and related compounds. J Pharm Sci 1991;80:387-93.
Dhanaraju MD, Kumaran KS, Baskaran T, Sree Ram Moorthy M. Enhancement of bioavailability of griseofulvin by its complexation with β-Cyclodextrin. Drug Dev Ind Pharm 1998;24:583-7.
Wessel W. Polyvinylpyrrolidone (PVP), its diagnostic, therapeutic and technical application and consequences thereof. In: Rowe RC, Sheshkey PJ, Quinn ME, editors. Handbook of pharmaceutical excepients, sixth edition. IL: Pharmaceutical Press; 2009. p. 581-4.
Collett JH. Poloxamer. In: Rowe RC, Sheshkey PJ, Quinn ME, editors. Handbook of pharmaceutical excepients, sixth edition. IL: Pharmaceutical Press; 2009. p. 507-9.
Sastry AV, Khan MA. Aqueous-based polymeric dispersion: face-centered cubic design for the development of atenolol gastrointestinal therapeutic system. Pharm Dev Technol 1998;3:423–32.
Jumaa M, Kleinebudde P, Muller BW. Physicochemical properties and hemolytic effect of different lipid emulsion formulations using a mixture of emulsifiers. Pharm Acta Helv 1999;73:293–30.
Gao P, Witt MJ, Haskell RJ, Zamora KM, Shifflett JR. Application of a mixture experimental design in the optimization of a self-emulsifying formulation with a high drug load. Pharm Dev Technol 2004;9:1–9.
El-Malah Y, Khanfar NM, Nazzal S. D-Optimal mixture design: optimization of ternary matrix blends for controlled zero-order drug release from oral dosage forms. Drug Dev Ind Pharm 2006;32:1207-18.
El-Malah Y, Nazzal S. Real-time†disintegration analysis and D-optimal experimental design for the optimization of diclofenac sodium fast-dissolving films. Pharm Dev Technol 2013;18:1355-60.
Li B, Wen M, Li W, He M, Xang X, Li S. Preparation and characterization of baicalin-poly-vinylpyrrolidone coprecipitate. Int J Pharm 2011;408:91-6.
Townley ER Griseofulvin. In: Florey K, editor. Analytical profiles of drug substances. New York: Academic Press; 1979. p. 228–9.
Vo CL, Park C, Lee B. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Bio Pharm 2013;85:799-813.