Stacking complexation by nicotinamide: A useful way of enhancing drug solubility

• Published in: International journal of pharmaceutics Vol. 336; no. 1; pp. 35 - 41
• Main Authors: Sanghvi, Ritesh, Evans, Daniel, Yalkowsky, Samuel H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.05.2007; Elsevier
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Algorithms; beta-Cyclodextrins - chemistry; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Electric Conductivity; Estrone - chemistry; General pharmacology; Griseofulvin - chemistry; Medical sciences; Molecular Structure; Niacinamide - chemistry; Nicotinamide; Pharmaceutical Preparations - chemistry; Pharmaceutical Solutions - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmaceutical Vehicles - chemistry; Pharmacology. Drug treatments; Self-association; Solubility; Solubilization; Stacking; Surface Tension; Temperature; Water - chemistry; Nicotinamide; Self-association; Solubilization; Stacking; Drug; Complexation; Pharmaceutical technology; Solubility; B-Vitamins; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.11.025

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.