OPTIMIZATION OF TOPICAL RAPAMYCIN: CHEMICAL, PHYSICAL AND
MICROBIOLOGICAL STABILITY
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 were: chemical (extraction with lipophilic solvents
and high-performance liquid chromatography assay), physical (pH,
uniformity, extensibility, absence of crystals, absence of phase
separation and only for liposomal formulation was determined particle
size, zeta potential and encapsulation efficiency) and microbiological
(culture samples in blood-agar media) during 56 days. Results: only
liposomes were chemically, physically and microbiologically stable after
8 weeks. Ointment, emulsion and gel formulations lost their chemical and
physical stability before 56 days. Conclusions: this study describes a
new four formulations to improve the previously treatment for facial
angiofibromas in tuberous sclerosis. It also provides favorable
stability data only for liposomes. However, more dermokinetic and
clinical studies are needed to confirm that liposomes are most
appropriate to ensure effectiveness, safety and high patient
satisfaction.