Open AccessEffect of pH and water‐soluble polymers on the aqueous solubility of nimesulide in the absence and presence of β‐cyclodextrin derivatives
Author(s) -
Alexanian Christina,
Papademou Helen,
Vertzoni Maria,
Archontaki Helen,
Valsami Georgia
Publication year - 2008
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/jpp.60.11.0003
Subject(s) - nimesulide , solubility , chemistry , aqueous solution , sonication , polymer , nuclear chemistry , cyclodextrin , carboxymethyl cellulose , methyl cellulose , inclusion compound , polyvinylpyrrolidone , organic chemistry , cellulose , polymer chemistry , chromatography , sodium , biochemistry
The aqueous solubility of nimesulide in the absence and presence of β‐cyclodextrin (β‐CD) and its alkyl derivatives hydroxypropyl‐β‐CD and methyl‐β‐CD was studied. We also investigated the effect of water‐soluble polymers, hydroxypropylmethyl‐cellulose, sodium‐carboxymethyl‐cellulose, polyvinyl‐ pyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25°C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K , of the inclusion complexes formed calculated. β‐CDs increased the aqueous solubility of nimesulide in the following order: methyl‐β‐CD > β‐CD > hydroxypropyl‐β‐CD. Addition of hydroxypropylmethyl‐cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three β‐CDs with nimesulide, while preheating of the polymer at 70°C under sonication resulted in an additional two‐fold increase in the aqueous solubility of the drug. Sodium‐ carboxymethyl‐cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus β‐CD, hydroxypropyl‐β‐CD and methyl‐β‐CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl‐ cellulose in order to enhance its oral bioavailability.