Effect of a mixture of caffeine and nicotinamide on the solubility of vitamin (B 2) in aqueous solution

• Published in: European journal of pharmaceutical sciences Vol. 28; no. 1; pp. 59 - 66
• Main Authors: Evstigneev, M.P., Evstigneev, V.P., Santiago, A.A. Hernandez, Davies, D.B.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.05.2006; Elsevier
• Subjects: Algorithms; Biological and medical sciences; Caffeine; Caffeine - chemistry; Chemistry, Pharmaceutical; Drug Combinations; General pharmacology; Hetero-association; Medical sciences; Models, Molecular; Niacinamide - chemistry; Nicotinamide; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Riboflavin - chemistry; Solubility; Solutions; Vitamin B 2; Vitamins - chemistry; Water; Nicotinamide; Hetero-association; Solubility; Caffeine; Vitamin B 2; Pharmaceutical technology; CNS stimulant; Psychotropic; B-Vitamins; Mixture; Respiratory analeptic; Xanthine derivatives; Solubility Caffeine Nicotinamide Vitamin B2 Hetero-association; Aqueous solution; Physicochemical properties
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2005.12.010

The effect of caffeine (CAF) and nicotinamide (NMD) on the solubility of a vitamin B 2 derivative (FMN) has been evaluated for mixtures containing either a single hydrotrope (CAF or NMD) or the two hydrotropes simultaneously. A model for analysis of ternary systems, which takes into account all possible complexes between the molecules, has been developed and tested with experimental NMR data on the three-component mixture FMN–CAF–NMD. The results indicate that special attention should be given to the concentration of a hydrotropic agent used to enhance the solubility of a particular drug. A decrease in the efficacy of solubility of the vitamin on addition of large amounts of hydrotropic agent is expected in the two-component systems due to the increased proportion of self-association of the hydrotrope. It is found that a mixture of two hydrotropic agents leads to an increase in the solubility of the vitamin in three-component compared to the two-component system. Rather than using just one hydrotropic agent, it is proposed that a strategy for optimising the solubility of aromatic drugs is to use a mixture of hydrotropic agents.