In vivo efficacy of enabling formulations based on hydroxypropyl-[beta]-cyclodextrins, micellar preparation, and liposomes for the lipophilic cannabinoid CB2 agonist, MDA7

• Published in: Journal of pharmaceutical sciences 2013-02, Vol.102 (2), p.352
• Main Authors: Astruc-Diaz, Fanny, Mcdaniel, Steven W, Xu, Jijun J, Parola, Stéphane, Brown, David L, Naguib, Mohamed, Diaz, Philippe
• Format: Article
• Language: English
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23393

Enabling formulations based on hydroxypropyl-[beta]-cyclodextrins (HP[beta]CD), micellar preparation, and liposomes have been designed to deliver the racemic mixture of a lipophilic cannabinoid type 2 agonist, MDA7. The antiallodynic effects of MDA7 formulated in these three different systems were compared after intravenous (i.v.) administration in rats. Stoichiometry of the inclusion complex formed by MDA7 in HP[beta]CD was determined by continuous variation plot, electrospray ionization-mass spectrometry (ESI-MS) analysis, phase solubility, and nuclear magnetic resonance studies and indicate formation of exclusively 1:1 adduct. Morphology and particle sizes determined by dynamic light scattering and transmission electron microscopy show the presence of a homogeneous population of closed round-shaped oligolamellar MDA7 containing liposomes, with an average size of 118nm [polydispersity index (PDI) 0.03]. Monodisperse micelles exhibited an average size of 14nm (PDI 0.09). HP[beta]CD-based formulation administrated in vivo was composed of two discrete particles populations with a narrow size distribution of 3nm (PDI 0.04) and 510nm (PDI 0.02). HP[beta]CD-based formulation dramatically improved antiallodynic effect of MDA7 in comparison with the liposomes preparation. Through inclusion complexation and possibly formation of aggregates, HP[beta]CD can enhance the aqueous solubility of lipophilic drugs, thereby improving their bioavailability for i.v. administration. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:352-364, 2013 [PUBLICATION ABSTRACT]