DISCUSSION
This study concludes that only one of the four proposed formulations, liposomes, maintain their chemical, physical and microbiological stability throughout all the sampling time, awarding them a validity period of 56 days.
For the ointment and gel formulations, the chemical stability was the determining factor for not reaching the validity period of 56 days, with T90 = 56 and 21 days, respectively. In the case of the emulsion formulation, the physical stability was very obviously compromised after pre-separation of phases at t=14 days and a definitive breakdown of the emulsion at t=21 days. All formulations were microbiologically stable throughout the sampling period. Considering all stability studies, the validity period for each formulation was: ointment=42 days, emulsion=7 days, gel=14 days and liposomes=56 days.
Rapamycin is a highly apolar active substance. This stability study confirms that rapamycin is more comfortable among lipophilic excipients, such as petrolatum and liposomes. In hydrophilic vehicles it tends to precipitate and lose its physical and chemical stability, as in the case of emulsion and gel formulations.
Regarding excipients, transcutol allows a greater solubility of rapamycin in the vehicle (10), thus avoiding possible precipitations of the active principle and constituting a significant improvement in the formulation.
The liposomal formulation has certain advantages over the ointment formulation: it has a better appearance, more comfortable and better extensibility. Historically, some patients complained that classic ointment was difficult to apply (21) and these enhanced organoleptic properties of liposomal formulation would help increase compliance with treatment and patient satisfaction with topical therapy.
Additionally, liposomes have been studied as carriers of molecules for immunosuppressive therapies and chemotherapy (22,23). Liposome-encapsulated rapamycin has been shown to have the ability to reach the drug’s site of action more quickly, with antiproliferative properties on T cells (23,24).
Therefore, liposomes exert their influence on the stratum corneum of the skin, improving the penetration of the active substance and providing increased bioavailability of rapamycin. This property makes liposomes particularly effective for cosmetic and pharmaceutical use.
In these therapies, the role of the hospital pharmacists is key in the preparation of the formulations, since rapamycin was added to NIOSH list as a hazardous drug in 2014 (25), which results in greater control in the development of topical formulations (26). In addition, pharmaceutical care has special relevance in the process of dispensing, administration and monitoring, promoting the supervision and control of these patients.
After galenic improvement and confirmation of stability liposomes, more dermokinetic and clinical studies are needed to ensure effectiveness, safety and high patient satisfaction.