Effect of Isopropyl Myristate on Transdermal Permeation of Testosterone From Carbopol Gel.
The objective of the present study was to investigate the effect of isopropyl myristate (IPM) on the in vitro permeation of testosterone through human cadaver skin from carbopol gels. Six testosterone gel formulations were prepared using different IPM contents of 0%, 0.4%, 0.7%, 1%, 2%, and 3%. The gels were characterized for drug permeation, matrix morphology, pH, kinetics of ethanol evaporation, and viscosity. Mass balance studies were performed to estimate testosterone distribution among the compartments of diffusion cells. All formulations exhibited pH values of 5.1 and viscosities of 1.25-1.75 Pa.s depending on IPM contents. Under occlusive condition, testosterone flux was found to increase significantly (p < 0.05) by increasing IPM content. Gels containing 2% IPM exhibited 11-fold increase in flux compared with formulation devoid of IPM. Ethanol was found to have a synergistic effect with IPM in enhancing testosterone flux. Mass balance analysis showed that testosterone was in a saturated state in the skin. Conducting permeation experiments under nonocclusive condition was nondiscriminating because of the evaporation of alcohol and consequent precipitation of drugs. Based on demonstrated effect of IPM on product performance, the final IPM concentration should be controlled with minimal variation during manufacturing and shelf life of drug product.
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland 20993. Electronic address: Ahmed.Zidan@fda.hhs.gov.
Ahmed S
AS
Zidan
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland 20993.
Nahid
N
Kamal
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland 20993.
Alaadin
A
Alayoubi
Division of New Drug Products II, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland 20993.
Mark
M
Seggel
Division of New Drug Products II, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland 20993.
Sarah
S
Ibrahim
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, College Station, Texas 78363.
Ziyaur
Z
Rahman
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland 20993.
Celia N
CN
Cruz
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Maryland 20993.
Muhammad
M
Ashraf
D000180:Acrylic Resins / Q000737:chemistry*; D000279:Administration, Cutaneous; D004337:Drug Carriers / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D006801:Humans; D009226:Myristates / Q000737:chemistry*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013739:Testosterone / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000180:Acrylic Resins; D004337:Drug Carriers; D005782:Gels; D009226:Myristates; C006912:carboxypolymethylene; C008205:isopropyl myristate; D013739:Testosterone
carbopol gel; isopropyl myristate; testosterone; transdermal permeation; viscosity