A FACTORIAL STUDY ON THE EFFECTS OF HYDROXYPROPYL β CYCLODEXTRIN AND POLOXAMER ON THE SOLUBILITY AND DISSOLUTION RATE OF NIMESULIDE

The objective of the study is to evaluate the individual and combined effects of hydroxy propyl β cyclodextrin (HPβCD), surfactant (Poloxamer 407) on the solubility and dissolution rate of nimesulide, a BCS class II drug in a series of 2² factorial experiments. The solubility of nimesulide in four selected fluids containing HPβCD and Poloxamer 407 as per a 2² factorial study was determined. HPβCD alone gave a marginal increase (1.47 fold) in the solubility of nimesulide. Whereas Poloxamer 407 alone and combination of HPβCD and Poloxamer 407 gave a significantly higher enhancement in the solubility of nimesulide, 2.5 and 6.52 fold respectively. Solid inclusion complexes of nimesulide- HPβCD were prepared with and without Poloxamer 407 by kneading method as per a 2²-factorial design. Both the individual and combined effects of HPβCD and Poloxamer 407 on the solubility, dissolution rate and dissolution efficiency (DE₃₀) of nimesulide were highly significant (P < 0.01). HPβCD and Poloxamer 407 alone gave 13.17 and 5.20 fold increase in the dissolution rate of nimesulide. Combination of HPβCD and Poloxamer 407 gave a markedly higher enhancement (21.79 fold) in the dissolution rate of nimesulide. HPβCD in combination with Poloxamer 407 gave much higher enhancement in the solubility and dissolution rate of nimesulide than is possible with them individually.  Hence a combination of HPβCD and Poloxamer 407 is recommended to enhance the solubility and dissolution rate of nimesulide.