TY - JOUR
T1 - Stacking complexation by nicotinamide
T2 - A useful way of enhancing drug solubility
AU - Sanghvi, Ritesh
AU - Evans, Daniel
AU - Yalkowsky, Samuel H.
PY - 2007/5/4
Y1 - 2007/5/4
N2 - The solubility enhancement of 11 poorly soluble drugs by complexation using nicotinamide has been studied. The solubilization efficiency of nicotinamide has been compared to that of hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin. Solubility enhancements as high as 4000-fold are observed in 20% (w/v) nicotinamide solution. Furthermore, nicotinamide is more effective than cyclodextrins for solubilizing some of the drugs. The mechanism of drug solubilization by nicotinamide is investigated by studying the effects of nicotinamide concentration on the surface tension and the conductivity of water. A slight break in both, the surface tension and conductivity is noticed at around 10% (w/v), suggesting self-association at higher concentrations. Corresponding breaks in the solubility profiles of estrone and griseofulvin at similar concentrations support self-association. Based on this observation it appears that at low concentrations, one molecule of nicotinamide undergoes complexation with one drug molecule to form a 1:1 complex. At higher concentrations, two molecules of nicotinamide undergo complexation with one drug molecule forming a 1:2 complex. The complexation constants have been calculated for all the drugs and the data are well described by this model. Expectedly, increasing the temperature reduces the complexation constants.
AB - The solubility enhancement of 11 poorly soluble drugs by complexation using nicotinamide has been studied. The solubilization efficiency of nicotinamide has been compared to that of hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin. Solubility enhancements as high as 4000-fold are observed in 20% (w/v) nicotinamide solution. Furthermore, nicotinamide is more effective than cyclodextrins for solubilizing some of the drugs. The mechanism of drug solubilization by nicotinamide is investigated by studying the effects of nicotinamide concentration on the surface tension and the conductivity of water. A slight break in both, the surface tension and conductivity is noticed at around 10% (w/v), suggesting self-association at higher concentrations. Corresponding breaks in the solubility profiles of estrone and griseofulvin at similar concentrations support self-association. Based on this observation it appears that at low concentrations, one molecule of nicotinamide undergoes complexation with one drug molecule to form a 1:1 complex. At higher concentrations, two molecules of nicotinamide undergo complexation with one drug molecule forming a 1:2 complex. The complexation constants have been calculated for all the drugs and the data are well described by this model. Expectedly, increasing the temperature reduces the complexation constants.
KW - Nicotinamide
KW - Self-association
KW - Solubilization
KW - Stacking
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U2 - 10.1016/j.ijpharm.2006.11.025
DO - 10.1016/j.ijpharm.2006.11.025
M3 - Article
C2 - 17145146
AN - SCOPUS:34047273912
SN - 0378-5173
VL - 336
SP - 35
EP - 41
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1
ER -