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Solubilization of hydrophobic drugs clozapine and oxcarbazepine in the lower and higher molecular weight pluronic mixed micelles-a physicochemical, In vitro release and In vitro anti-oxidant study

Lookup NU author(s): Dr Pankaj Singla, Professor Marloes PeetersORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

In this work, we studied the solubilization capacityof the hydrophobic drugs Clozapine (CLZ) and Oxcarbazepine (OXC) in mixed micelles of low molecular weight pluronics (L64 and L35) and high molecular weight pluronics (P84, F127, F68 and P123) using UV–visible spectroscopy. The drug solubility, drug loading efficiency, the micelle–water partition coefficient (P), and Gibbs free energy (ΔG°) of solubilization were measured. From the obtained results, we concluded that the highest solubility of CLZ was observed in binary mixture of L64/P84 (1:4) due to the hydrophobic nature of these pluronics. In the case of OXC, the highest solubility was observed in L64/F127(1:4)because the drug solubilized both in the core and the corona region of F127 since OXC contains a carboxamide polar moiety. Fluorescence spectroscopy indicated that the critical micelle concentration (cmc) decreased with the formation of mixed micelles as compared to pure individual micelles. From DLS measurements, it was observed that there was an increase in size of mixed micelles from mixed micelles to drug (CLZ and OXC) loaded mixed micelles. In vitro release study of CLZ showed that as the amount of P84 in binary mixed micelles decreases, the release was faster. The formulations were also screened for antioxidant activity by four different methods. The antioxidant activity was significantly increased in the binary mixture of the pluronic solutions, indicated that pluronic formulations can be considered as an effective drug delivery candidate in the management of diseases that affect the central nervous system.


Publication metadata

Author(s): Singla P, Garg S, Bhatti R, Peeters M, Singh O, Mahajan RK

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Liquids

Year: 2020

Volume: 317

Print publication date: 01/11/2020

Online publication date: 15/07/2020

Acceptance date: 12/07/2020

Date deposited: 14/08/2020

ISSN (print): 0167-7322

ISSN (electronic): 1873-3166

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.molliq.2020.113816

DOI: 10.1016/j.molliq.2020.113816


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Funding

Funder referenceFunder name
EPRC
EP/R029269/2

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