title: Effect of vehicle systems, pH and enhancers on the permeation of highly lipophilic aripiprazole from Carbopol 971P gel systems across human cadaver skin.
abstract: The objective of this study was to investigate the effect of vehicle systems, pH and enhancers on the permeation of a highly lipophilic basic drug aripiprazole (ARPZ) through human cadaver skin. Solubility of ARPZ in single, binary, tertiary, and quaternary vehicle systems of N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), water, ethanol and isopropyl myristate (IPM) was studied. Gel formulations of 5% ARPZ were developed with 0.5% Carbopol 971P in quaternary vehicle systems consisting of NMP, DMSO, water and ethanol or IPM at optimum ratio of 40/40/5/15. The effect of pH of the gel formulations and fatty acids with different chain lengths on the permeation was studied. The flux of ARPZ from gel formulation with IPM and ethanol was comparable. A four fold increase in APRZ flux was observed when the pH of the gel systems was lowered from pH 8.2 to pH 6 or pH 7. For fatty acids, the order of flux is lauric acid > myristic acid > caprylic acid > oleic acid. In all the cases, in vitro permeation rate of ARPZ through human cadaver skin followed zero order kinetics. This study demonstrated that ARPZ in tertiary vehicle system of NMP/DMSO/water/IPM at ratio of 40/40/5/15 and gel system of Carbopol 971P with pH 7 is a promising candidate for transdermal delivery.
authors: Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201-5372, USA. anwar.hossain@tevausa.com
authors: Muhammed Anwar
authors: MA
authors: Hossain
authors: Salah U
authors: SU
authors: Ahmed
authors: Fotios M
authors: FM
authors: Plakogiannis
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000279:Administration, Cutaneous; D014150:Antipsychotic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D000068180:Aripiprazole; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000378:metabolism; D005782:Gels / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics*; D015363:Quinolones / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D000179:Acrylates; D014150:Antipsychotic Agents; D005227:Fatty Acids; D005782:Gels; D014677:Pharmaceutical Vehicles; D010879:Piperazines; D015363:Quinolones; C492577:carbopol 971P; D000068180:Aripiprazole