Short- and Long-Term Stability Assessment of a New Injectable Diazepam Submicron Emulsion

Abstract

An innovative diazepam injectable emulsion, recently characterized, was submitted to short-and long-term stability studies. The initial pH of the diazepam emulsion decreased progressively with time. However, this pH decrease can be controlled by adjusting the initial pH of the emulsion. At initial adjusted pH of 7.4 or 8.0, the pH decrease of the emulsions was markedly diminished as confirmed by pHfollow-up over 10 months storage. All the emulsions prepared using less than 25% oily phase remained stable at the various storage temperatures over a 10 month period. However, emulsion stability was highly dependent on the non-ionic emulsifier concentration, while both low and high phospholipid concentrations reduced emulsion stability. Furthermore, the diazepam remained intact in the emulsion, as confirmed by HPLC when stored at 4° and 25°C over a 16-month storage period. The optimal emulsion formulation was stable to conventional steam sterilization cycles. Exposure of the emulsion to mechanical stress conditions did not affect the integrity of the emulsion, indicating that the dosage form developed remained practically stable.