A FACTORIAL STUDY ON THE ENHANCEMENT OF DISSOLUTION RATE OF VALDECOXIB BY SOLID DISPERSION IN COMBINED CARRIERS

Valdecoxib, a widely prescribed anti-inflammatory and analgesic drug belongs to class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. As such it needs enhancement in the dissolution rate and bioavailability to derive its maximum therapeutic efficacy. The objective of the present study is to prepare and evaluate solid dispersions of valdecoxib in combined carriers, a water dispersible new modified starch namely starch citrate and a water soluble surfactant namely Poloxamer 407 for enhancing the dissolution rate and dissolution efficiency of valdecoxib. The individual and combined effects of the modified starch, starch citrate and Poloxamer 407 in enhancing the dissolution rate and dissolution efficiency of valdecoxib were evaluated in a 22factorial study. Solid dispersions of valdecoxib in starch citrate and Poloxamer 407 alone and in combination were prepared as per 22 factorial design by kneading method and were evaluated for dissolution rate and dissolution efficiency. The dissolution rate (K1) and dissolution efficiency (DE30) of valdecoxib could be significantly enhanced by solid dispersion in starch citrate (a water dispersible modified starch) and Poloxamer 407 (a surfactant). ANOVA indicated that the individual and combined effects of starch citrate (factor A) and Poloxamer 407 (factor B) in enhancing the dissolution rate (K1) and dissolution efficiency (DE30) are highly significant (P < 0.01). A 12.73 , 62.22 and 10.7 fold increase in the dissolution rate ( K1 ) and a 10.99, 28.56 and 13.11 fold increase in the dissolution efficiency (DE30) was observed respectively with solid dispersions SD a , SD b and SD ab when compared to F1 ( valdecoxib pure drug). Solid dispersion prepared employing Poloxamer 407 alone as carrier (SD b) gave highest enhancement in the dissolution rate (62.22 fold) and dissolution efficiency (28.56 fold) of valdecoxib. Combination of starch citrate with Poloxamer 407 has no additional advantage in enhancing the dissolution rate and dissolution efficiency of valdecoxib. Hence solid dispersion of valdecoxib in starch citrate and Poloxamer 407 alone is recommended to enhance the dissolution rate and dissolution efficiency of valdecoxib, a BCS class II drug.