Levy M Y, Benita S
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
J Parenter Sci Technol. 1991 Mar-Apr;45(2):101-7.
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 pH follow-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 degrees and 25 degrees 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.
一种最近被表征的创新型地西泮注射乳剂，已进行了短期和长期稳定性研究。地西泮乳剂的初始pH值随时间逐渐降低。然而，这种pH值降低可通过调节乳剂的初始pH值来控制。在初始调节pH值为7.4或8.0时，通过10个月储存期的pH值跟踪证实，乳剂的pH值降低明显减少。所有使用少于25%油相制备的乳剂在10个月期间的各种储存温度下均保持稳定。然而，乳剂稳定性高度依赖于非离子乳化剂浓度，而低和高磷脂浓度均会降低乳剂稳定性。此外，通过HPLC证实，地西泮在乳剂中保持完整，在4℃和25℃下储存16个月期间。最佳乳剂配方对常规蒸汽灭菌周期稳定。乳剂暴露于机械应力条件下不影响乳剂的完整性，表明所开发的剂型实际上保持稳定。
