Introduction

Topical rapamycin has been established as an effective and safe therapy for facial angiofibromas in tuberous sclerosis. Different formulations have been tested for this skin disease, most using an ointment as a vehicle.

Purpose

To improve the classical formulation of topical rapamycin and to determine the validity period of the proposed options based on chemical, physical, and microbiological stability studies.

Methods

Four different 0.4% rapamycin formulations were prepared (ointment, emulsion, gel, and liposomes). The stability studies for each formulation over 56 days were as follows: (1) chemical: extraction with different solvents and high-performance liquid chromatography assay; (2) physical: pH, uniformity, extensibility, absence of crystals, absence of phase separation, and only for liposomal formulation, particle size, zeta potential, and encapsulation efficiency were determined; and (3) microbiological: culture samples in blood-agar media.

Results

Only liposomes were chemically, physically, and microbiologically stable after 8 weeks. Ointment, emulsion, and gel formulations lost their chemical or physical stability before 56 days.

Conclusions

The authors describe four new formulations to improve the previous treatment for facial angiofibromas in tuberous sclerosis. The liposome-based formulation was the most appropriate according to chemical, physical, and microbiological stability studies. However, it would be necessary to carry out clinical studies to ensure the effectiveness and safety of this formulation and also guarantee an improvement in the quality of life of patients.

中文翻译：

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用于治疗罕见结节性硬化症的外用雷帕霉素的优化、配方和稳定性：从软膏到脂质体

介绍

外用雷帕霉素已被确定为治疗结节性硬化症中面部血管纤维瘤的有效且安全的疗法。已经针对这种皮肤病测试了不同的配方，大多数使用软膏作为载体。

目的

改进外用雷帕霉素的经典配方，并根据化学、物理和微生物稳定性研究确定所提议方案的有效期。

方法

制备了四种不同的0.4%雷帕霉素制剂（软膏剂、乳剂、凝胶剂和脂质体）。各制剂56天的稳定性研究如下：（1）化学：不同溶剂提取和高效液相色谱测定；(2)物理：测定pH、均匀性、延展性、无晶体、无相分离，并且仅针对脂质体制剂测定粒径、zeta电位和包封率；(3) 微生物学：在血琼脂培养基中培养样品。

结果

8 周后，只有脂质体在化学、物理和微生物学上保持稳定。软膏、乳液和凝胶制剂在 56 天之前就失去了化学或物理稳定性。

结论

作者描述了四种新配方，以改善结节性硬化症面部血管纤维瘤的先前治疗。根据化学、物理和微生物稳定性研究，基于脂质体的制剂是最合适的。然而，还需要进行临床研究以确保该制剂的有效性和安全性，并保证患者生活质量的改善。