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

Abstract

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 modified starch namely Starch 1500 and a water soluble
surfactant namely Poloxamer 188 for enhancing the dissolution rate and dissolution efficiency of valdecoxib in a 22 factorial
study. The individual and combined effects of Starch 1500 and Poloxamer 188 in enhancing the dissolution rate and dissolution
efficiency of valdecoxib were evaluated in a 22 factorial study. Solid dispersions of valdecoxib in Starch 1500 (a modified starch)
and Poloxamer 188 (surfactant) 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 1500 and Poloxamer 188. A 10.81, 12.98 and 19.93 fold increase in
the dissolution rate ( K1 ) and a 12.26, 10.12 and 15.07 fold increase in the dissolution efficiency (DE30) was observed
respectively with solid dispersions SD a , SD b and SD a b when compared to F1 (valdecoxib pure drug). Combination of Starch
1500 and Poloxamer 188 gave a markedly higher enhancement in the dissolution rate (K1) and dissolution efficiency (DE30) of
valdecoxib than is possible with them alone. ANOVA indicated that the individual and combined effects of Starch 1500 (factor A)
and Poloxamer 188 (factor B) in enhancing the dissolution rate (K1) and dissolution efficiency (DE30) are highly significant (P <
0.01).Hence solid dispersion of valdecoxib in combined carriers consisting of Starch 1500 and Poloxamer 188 is recommended to
enhance the dissolution rate and dissolution efficiency of valdecoxib, a BCS class II drug.