Development and chemical stability studies of alcohol-free Phenobarbital solution for use in pediatrics

Phenobarbital an anticonvulsant drug and tranquilizer, is frequently used in pediatric medicine usually as an oral solution. Due to the poor aqueous solubility, ethanol has been used as a cosolvent for increasing the solubility of Phenobarbital. Nowadays, there is a tendency to eliminate ethanol from oral preparations in general, particularly in pediatric medicine. Therefore, the aim of the present study was to investigate the solubility of Phenobarbital in various oral cosolvents and to present ethanol-free oral solution of Phenobarbital for pediatrics. The chemical stability of the solutions was also investigated.

In this research, mixtures of water, propylene glycol and glycerin were prepared with different ratios to obtain optimum solubility where crystallization and crystal growth did not occur at 4 ?C for a period of 2 months and the pH of the solutions was adjusted at 4.5. The results showed that only formulations containing 10-12% propylene glycol, 26-28% glycerin and 0-20% water had no crystal growth. Chemical stability (shelf-life) of the selected formulations was investigated using Arrhenius accelerated stability test. The chemical stability results showed that these formulations were stable over the period of 2 years.