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Abstract

ENHANCEMENT OF DISSOLUTION RATE OF OLMESARTAN BY SOLID DISPERSION IN CROSSPOVIDONE AND POLOXAMER 188 ALONE AND IN COMBINATION

K. P. R. Chowdary*, K. Ravi Shankar and M. Mercy Ruth

ABSTRACT

Olmesartan, a widely prescribed antihypertensive 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 olmesartan in Crosspovidone and Poloxamer 188 alone and in combination for enhancing the dissolution rate and dissolution efficiency of olmesartan. The individual and combined effects of the two carriers, Crosspovidone and Poloxamer 188 in enhancing the dissolution rate and dissolution efficiency of olmesartan were evaluated in a 22 factorial study.Solid dispersions of olmesartan in Crosspovidone alone were prepared using five ratios of drug: carrier namely 9:1, 8:2, 2:1, 1:1 and 1:3 by solvent evaporation method.Solid dispersions of olmesartan in Poloxamer 188 alone were prepared using three ratios of drug: carrier namely 19:1, 9:1 and 8: 2 by common solvent method.Solid dispersions of olmesartan in combined carriers namely Crosspovidone and Poloxamer 188 were prepared as per 22 factorial design. All the solid dispersions prepared were evaluated for drug content uniformity, dissolution rate and dissolution efficiency in comparison to olmesartan pure drug. The dissolution rate (K1) and dissolution efficiency (DE30) of olmesartan could besignificantly enhanced by solid dispersion in Crosspovidone (a water dispersible super disintegrant) and Poloxamer 188 (a nonionic surfactant) alone and in combination.Solid dispersions prepared employing Crosspovidone and Poloxamer 188 alone as carriersgave rapid and higher dissolution of olmesartan. With both the carriers, the dissolution rate and dissolution efficiency of olmesartan were increased as the percent of carrier in the solid dispersion was increased. Poloxamer 188 gave higher enhancement in the dissolution rate of olmesartan than Crosspovidone when used at the same concentration. All solid dispersions prepared as per 22 factorial design gave rapid and higher dissolution of olmesartan when compared to olmesartan pure drug.ANOVA indicated that the individual and combined effects of Crosspovidone (factor A) and Poloxamer 188 (factor B) in enhancing the dissolution rate (K1) of olmesartan are highly significant (P < 0.01) .A 5.67, 4.09 and 7.15 fold increase in the dissolution rate (K1) and a 4.77,3.53 and 5.58 fold increase in the dissolution efficiency (DE30) was observed respectively with solid dispersions Fa , Fb and Fa b when compared to F1 (olmesartan pure drug). The order of increasing dissolution rate (K1) and DE30 observed with various solid dispersions was Fab>Fa>Fb>F1. Combination of Crosspovidone (a water dispersible superdisintegrant) and Poloxamer 188 (a nonionic surfactant) gave a markedly higher enhancement in the dissolution rate (K1) and dissolution efficiency (DE30) of olmesartan than is possible with them alone.Hence solid dispersion of olmesartan in combined carriers consisting of Crosspovidone andPoloxamer 188 is recommended to enhance the dissolution rate and dissolution efficiency of olmesartan, a BCS class II drug.

Keywords: Solid dispersions, Olmesartan, Crosspovidone, Poloxamer188, Factorial study.


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