Liposomal formulation and pharmacokinetic study of CPD409, a novel sodium channel blocker

Abstract

CPD409 is a novel sodium channel blocker for pain control in chemotherapy-induced peripheral neuropathy with a very poor water solubility of less than 10 μg/mL. The aim of this study is to improve the aqueous solubility of CPD409 by using inclusion complexes with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes were prepared by two different methods; common solvent evaporation (CSE) and freeze-drying (FD) method. The phase solubility study indicated that HP-β-CD showed 3-times higher formation constant with CPD409 than β-CD. Inclusion complexes at a molar ratio of 1:2 increased the solubility of CPD409 by 130 times when compared with pure CPD409. The physicochemical characterization of the prepared formulation confirmed the formation of CPD409/HP-β-CD inclusion complexes. In dissolution study, inclusion complexes at a molar ratio of 1:2 released 70% of CPD409 but CSE method showed more rapid dissolution profile than FD method. Pharmacokinetic study also showed an increased bioavailability in 1:2 formulation compared to pure CPD409. In conclusion, inclusion complexes of CSE and FD method at a molar ratio of 1:2 showed increased solubility, dissolution rate, and bioavailability of CPD409. Therefore, complexation of CPD409 with HP-β-CD using CSE and FD method at a molar ratio 1:2 can be promising strategy for effective oral delivery.