Background Facial angiofibromas in tuberous sclerosis are an aesthetic problem within the clinical context of the disease. There are currently few stability studies that allow selecting the best topical sirolimus therapy.
Purpose To improve the formulation of sirolimus 0.4% for the treatment of facial angiofibromas in tuberous sclerosis and to determine the period of validity (physical, chemical and microbiological stability) of the proposed formulations.
Material and methods Three formulations of sirolimus 0.4% were prepared (each in duplicate, A and B). Facilities and equipment: biological safety cabinet with individual protection equipment for the manipulator. Conditions: aluminum tubes, temperature 2°C–8°C.
Gel: sirolimus 0.4%, transcutol 10%, hydroxypropylmethylcellulose 2%, water for injection (API: sterile solution) c.s.p. 20 g.
Ointment: sirolimus 0.4%,transcutol 10%, lanolin 10%, shea butter 20%, vitamin E 1%, vaseline c.s.p. 20 g.
Emulsion: sirolimus 0.4%, transcutol 10%, absorption base W/O 20%, API c.s.p. 20 g.
Physical stability: pH was determined with reactive strips at t=15 and 30 days. Properties of uniformity, extensibility, absence of crystals and absence of phase separations were evaluated on the transparent surface according to three levels: level 1, at least favourable and level 3, the most favourable.
Chemical stability: percentage content of remaining sirolimus (%CR) in formulations A and B was determined at times (t)=0.1 and 2 days, and every 2 days until t=30 days, and t90 (sampling time at which it reached 90% of%CR), when%CR was ≤90%. Analytical method: high-performance liquid chromatography with ultraviolet/visible detection.
Microbiological stability: formulations A and B were incubated at 37°C on Mueller–Hinton agar and blood agar at t=15 and 30 days.
Results Physical stability: pH did not change on days 15 and 30: 6.0 for the gel and the emulsion and 7.0 for the ointment.
Gel: uniformity, level 3; extensibility, level 3; absence of crystals, level 3; absence of phase separations, level 3.
Ointment: uniformity, level 3; extensibility, level 1; absence of crystals, level 3; absence of phase separations, level 3.
c) Emulsion: uniformity, level 3; extensibility, level 2; absence of crystals, level 3; absence of phase separations, level 3.
Chemical stability: t90 was reached during the sampling period for the gel and emulsion formulations: t90=14 and 2 days, respectively.
%CR at t=30 days was 110.4 (SD ±0.4) for the gel, 101.2 (SD ±4.6) for the ointment and 87.7 (SD ±0.4) for the emulsion.
Microbiological stability: cultures were negative for three formulations (A and B) at t=15 and 30 days.
Conclusion Each formulation has its own galenic characteristics that must be considered. Three formulations of sirolimus 0.4% maintain the physical and microbiological stability at 30 days at 2°C–8°C. Only the ointment formulation maintains chemical stability, assigning a period of validity of 30 days at 2°C–8°C.
References and/or acknowledgements No conflict of interest.
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