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Enhancement of Solubility and Dissolution Rate of Nimesulide by Cyclodextrins, Poloxamer and PVP

K. P. R. Chowdary, K. Surya Prakasa Rao and Roshnara Shaik


The objective of the study is to evaluate the effects of two cyclodextrins ( β CD and HP β CD), surfactant (Poloxamer 407) and PVP on the solubility and dissolution rate of nimesulide in a series of 2 3 factorial experiments. The solubility of nimesulide in eight selected fluids containing CDs, Poloxamer 407 and PVP as per 2 3 factorial study was determined in each case. The solubility of nimesulide was markedly enhanced by β CD (4.12 fold), HP β CD (21.06 fold), Poloxamer 407 (5.37 fold) and PVP (24.9 fold) individually. β CD in combination with Poloxamer 407 and PVP gave respectively 5.44 and 26.31 fold increase in the solubility of nimesulide. HP β CD in combination with Poloxamer 407 and PVP gave respectively 5.31 and 26.43 fold increase in the solubility of nimesulide. Poloxamer 407 in combination with PVP has given highest enhancement (28.06 fold) in the solubility of nimesulide. Both the individual and combined effects of cyclodextrins, Poloxamer a nd PVP on the solubility of nimesulide were highly significant (P < 0.01). Solid inclusion complexes of nimesulide-CDs ( β CD and HP β CD) were prepared with and without Poloxamer 407 and PVP by kneading method as per 2 3 -factorial design. ANOVA indicated that the individual main effects of CDs ( β CD and HP β CD), Poloxamer 407 and PVP and their combined effects in enhancing the dissolution rate (K 1 ) were highly significant (P < 0.01). β CD alone gave a 9.63 fold increase in the dissolution rate of nimesulide. β CD in combination with PVP and Poloxamer 407 gave respectively 15.51 and 21.78 fold increase in the dissolution rate of nimesulide. HP β CD alone gave a 10.88 fold increase and in combination with PVP and Poloxamer 407 it gave respectively 37.72 and 51.61 fold increase in the dissolution rate of nimesulide. Combination of CDs with Poloxamer 407 and PVP has markedly enhanced both the solubility and dissolution rate of nimesulide, a BCS class II drug.


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