Liposomal formulation and pharmacokinetic study of CPD409, a novel sodium channel blocker
- Authors
- Lee, Ga Hee; Shin, Dae Hwan; Suh, Hong-Won; Lee, Jae-Yong; Lim, Soon Sung; Kim, Jin-Seok
- Issue Date
- Sep-2019
- Publisher
- Springer Netherlands
- Keywords
- CPD409; Dissolution; Oral delivery; Pharmacokinetics; Solubilization; β-Cyclodextrin
- Citation
- Journal of Pharmaceutical Investigation, v.49, no.5, pp 565 - 573
- Pages
- 9
- Journal Title
- Journal of Pharmaceutical Investigation
- Volume
- 49
- Number
- 5
- Start Page
- 565
- End Page
- 573
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/2857
- DOI
- 10.1007/s40005-019-00445-z
- ISSN
- 2093-5552
2093-6214
- Abstract
- Purpose: 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). Methods: The inclusion complexes were prepared by two different methods; common solvent evaporation (CSE) and freeze-drying (FD) method. Results: 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. Conclusion: 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. © 2019, The Korean Society of Pharmaceutical Sciences and Technology.
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