Optimization, Formulation, and Stability of Topical Rapamycin Used for Rare Tuberous Sclerosis Disease: from Ointment to Liposomes

Abstract

Abstract 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.