US EPA

1136363 

Journal Article 

Solubility behaviour of rofecoxib in individual solvents using the concept of partial solubility parameters 

Sathesh, BPR; Subrahmanyam, CVS; Manavalan, R; Valliappan, K 

2008 

1 

Indian Journal of Pharmaceutical Education & Research
ISSN: 0019-5464 

42 

2 

161-169 

English 

WOS:000259499100011 

The solubility behaviour of rofecoxib in individual solvents ranging from non-polar to highly polar was studied. For understanding the solute-solvent interactions, partial solubility parameters concept was utilized. The extended Hansen's method was used for analysing the solubility data and partial solubility parameters of rofecoxib were obtained. The Flory-Huggins size correction term 'B' was found to improve the prediction of solubility. The four-parameter approach involving proton-donor and proton-acceptor parameters was also used in fitting the solubility data. Though correlation coefficients are appreciable, a high error was observed in a few solvents particularly in n-alcohol series. From 31 solvents, the normal alcohols were omitted and further analysis was done. The correlations were improved by 5 to 7% (R-2 = 0.95). Rofecoxib exhibited the hydrogen bonding in methanol and ethanol, where as the hydrophobic interaction in n-octanol. This type of dual behaviour of rofecoxib might be responsible for variations in the solubility predictions and determination of partial solubility parameters. The dipolar interaction term (delta(p)) exhibited a considerable variation and the hydrogen bonding parameter (delta(h)) exhibited the consistent interaction. The total solubility parameter of rofecoxib may be in the range of 10 to 11 H. 

solubility behaviour; extended Hansen's approach; Flory-Huggins size correction; four parameter approach; partial solubility parameters; rofecoxib