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.