Utilization of nicotinamide as a complexing agent in the formulation of diazepam oral solution I

ABSTRACT

Diazepam is a benzodiazepine tranquilizer. It has limited aqueous solubility. Nicotinamide is a safe., non- toxic and non- irritating vitamin, used to enhance the solubility of poorly soluble drugs. In this study a new approach was achieved to prepare diazepam solution through utilizing nicotinamide as a complexing agent. The results indicated that the use of nicotinamide gave soluble and more stable formula for diazepam oral solution, where the shelf- life was about 6 years, compared to 2 years when using co-solvent alone. The results showed that combination of nicotinamide and co-solvent [s] together in the formulation lead to reduction in the amount of both of them, at the same time this combination reduced the shelf-life of the solutions in comparison to that containing nicotinamide alone. The results also indicated that diazepam undergoes hydrolysis at low and high PH in the prepared formulations with optimum stability at PH5 which is the most suitable one for the formulations. In addition the results showed that the buffer type, buffer concentration and ionic strength had no effect on the rate of hydrolysis of diazepam, in spite of its photochemical decomposition, with a shelf-life of 5.9 months. The results also indicated that diazepam was unstable when formulated in plastic containers with a loss of 24% of the drug with 4 months. The results of this study showed the successful use of nicotinamide as a complexing agent in the formulation of diazepam oral solution