Introduction: Cannabidiol (CBD), the main non-psychotropic cannabinoid, has emerged as a potential therapeutic agent for the treatment of several disorders including cancer, neurodegenerative disorders and pain among others. However, its low aqueous solubility hinders the development of effective parenteral formulations [1]. The use of polymeric microparticles as CBD carriers could resolve this challenge and allows to obtain an extended CBD release after a single administration [2]. Among all the available polymers, poly(lactic-co-glycolic acid) (PLGA), FDA approved for various medical applications, is one the most used. Ionizing radiation has been proposed as an effective sterilizing method for PLGA microparticles, which is essential for their parenteral administration [3].
The aim of this work was to evaluate the effect of gamma sterilization on the characteristics of CBD loaded microparticles.
Methods: Microparticles with a CBD:PLGA ratio of 10:100 (10-Mps) and 20: 100 (20-Mps) were prepared by solvent evaporation technique, using PLGA-RG-502 as polymer, and sterilized by gamma irradiation at a dose of 25 kGy. All formulations were then characterized by DLS, SEM and DSC. CBD content and CBD release were also evaluated by HPLC.
Results: No differences in particle morphology and particle size were detected between sterile and non-sterile formulations. All microparticles exhibited a spherical shape, a smooth surface, and an average particle size around 25 µm. DSC analysis showed the absence of the CBD melting peak in sterile and non-sterile CBD microparticles, indicating that it is dissolved or molecularly dispersed within the polymeric matrix and that no crystallization processes occurred during sterilization. However, a reduction on PLGA glass transition was appreciated in both 10-Mps and 20-Mps sterile formulations compared with their non-sterile counterparts. A significant lower CBD content was also detected in sterile microparticles, observing a CBD degradation during sterilization of 13.75% and 10.28% in 10-Mps and 20-Mps respectively. Finally, a faster CBD release was appreciated in sterile microparticles compared with their counterparts, due to the faster PLGA degradation in sterilized microparticles.
Conclusions: Due to the CBD degradation during sterilization process and the acceleration of the release of this drug from PLGA microparticles, gamma irradiation is not an adequate method to sterilize CBD-PLGA-microparticles.
References:
[1]. Fraguas et.al. Drugs. 2018; 78(16):1665-1703.
[2]. Fraguas et.al. Int J Pharm.202; 574:118916
[3]. De Oliveira et.al. Mater Sci Eng C Mater Biol Appl. 2017; 80:438-448.
