Nishikawa Masato, Onuki Yoshinori, Okuno Yoshihide, Takayama Kozo
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Chem Pharm Bull (Tokyo). 2011;59(3):332-7. doi: 10.1248/cpb.59.332.
This study investigated the relationship between the state of water and the dispersion stability of a skin cream formulation. Hydrophilic ointments treated with a high-pressure wet-type jet mill were used as model formulations. Spin-lattice relaxation times (T(1)) were measured by magnetic resonance techniques to estimate the state of water in samples. A shorter T(1) relaxation time was obtained from samples with higher surfactant content, whereas the processing pressure of the jet mill and 1-week storage at 40 °C did not influence the T(1) relaxation time. Observations using scanning electron microscopy (SEM) showed that coalescence occurred in samples with lower surfactant contents (1.0% by weight) following 1-week storage at 40 °C. We also investigated samples prepared using a hydrophilic surfactant with a short polyethylene glycol (PEG) chain and with PEG-4000. From the change in T(1) relaxation times after removing the oil phase from samples by centrifugation, it was clarified that most of the surfactant was located on the surface of oil droplets. Furthermore, SEM observations showed that phase separation was facilitated as the PEG chain length of the surfactant shortened. Thus, a thin water layer over oil droplets is the most important factor for stabilizing their dispersion. This study provides proof-of-principle results on the contribution of the state of water to the dispersion stability of a skin cream formulation.
本研究调查了水的状态与皮肤乳膏配方分散稳定性之间的关系。使用经高压湿式喷射磨处理的亲水性软膏作为模型配方。通过磁共振技术测量自旋晶格弛豫时间(T(1))以估计样品中水的状态。表面活性剂含量较高的样品获得了较短的T(1)弛豫时间,而喷射磨的加工压力和在40℃下储存1周并未影响T(1)弛豫时间。使用扫描电子显微镜(SEM)观察表明,在40℃下储存1周后,表面活性剂含量较低(重量百分比为1.0%)的样品中发生了聚结。我们还研究了使用具有短聚乙二醇(PEG)链的亲水性表面活性剂和PEG - 4000制备的样品。通过离心从样品中去除油相后T(1)弛豫时间的变化表明,大多数表面活性剂位于油滴表面。此外,SEM观察表明,随着表面活性剂PEG链长度缩短,相分离更容易发生。因此,油滴上的薄水层是稳定其分散的最重要因素。本研究提供了关于水的状态对皮肤乳膏配方分散稳定性贡献的原理验证结果。