Transdermal formulation of 4-benzylpiperidine for cocaine-use disorder

Abstract

Cocaine-use disorder is a major public health problem, yet there is no FDA approved treatment. The distinguished preclinical efficacy of 4-benzylpiperidine as substitute agonist for cocaine-use-disorder along with the therapeutic benefits of transdermal delivery, make it an excellent candidate for transdermal delivery. The purpose of this study was to investigate the in vitro transdermal delivery of 4-benzylpiperidine across dermatomed human skin. Mathematical models were used to calculate the theoretical and experimental drug percutaneous absorption. Gels were formulated with varying amount of gelling agent and subjected to rheological analysis. Franz cells were used to investigate the in vitro permeation. Transdermal permeation of 4-benzylpiperidine from propylene glycol solution (1, 10, 20 and 50 mg/mL) corresponded to 16%–31% delivery (49.45 ± 11.60, 258.47 ± 48.50, 600.26 ± 74.18, 1945.20 ± 405.59 μg/cm2). The average cumulative amount of drug delivered from gel formulation was 1824.90 ± 425.12 μg/cm2. Thixotropic test demonstrated 2% hydroxyl propyl cellulose based gel to have the highest structure recovery ratio. The calculated theoretical permeability coefficient and theoretical flux value (32.637 μg/cm2/h) predicted high percutaneous absorption. This was further validated by the experimentally determined permeability coefficients and flux values (62.73 ± 12.14 μg/cm2/h), demonstrating proficient transdermal delivery of 4-benzylpiperidine.