Drug and vehicle deposition from topical applications: use of in vitro mass balance technique with minoxidil solutions.
The disposition of minoxidil and propylene glycol from topical solutions was measured by using an in vitro mass balance technique. The experimental approach included assessment of the following compartments of the skin and the diffusion cell as a function of time: (1) donor compartment; (2) hairless mouse skin surface, epidermis, and dermis; and (3) receiver compartment. Excellent mass balance was achieved for minoxidil at three doses. However, the recovery of propylene glycol depended on both application volume and time. The experiment involving the evaporation of propylene glycol and water from the propylene glycol:ethanol:water (20:60:20, v/v) mixture, which was placed in the well of a tissue culture plate at room temperature and 37 degrees C, substantiated the loss of vehicles to the air. When a thin application of 20 microL/cm2 was used, 60% of the propylene glycol was unaccounted for after 16 h. The evaporation of propylene glycol concentrated the solution to supersaturation, precipitated out the drug, and then stabilized the thermodynamic activity of the drug in the vehicle. The amount of formulation applied influences the rate of concentration and, thus, the time at which minoxidil precipitates. The precipitation limits the amount of minoxidil that can be absorbed and leads to poor percutaneous absorption of drug from the formulation.
Tsai
J C
JC
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Cappel
M J
MJ
Flynn
G L
GL
Weiner
N D
ND
Kreuter
J
J
Ferry
J J
JJ
D000287:Administration, Topical; D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004058:Diffusion; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008914:Minoxidil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000493:pharmacokinetics; D012869:Skin Absorption; D012996:Solutions; D013816:Thermodynamics; D014316:Tritium
D002250:Carbon Radioisotopes; D014677:Pharmaceutical Vehicles; D011409:Propylene Glycols; D012996:Solutions; D014316:Tritium; D008914:Minoxidil; D019946:Propylene Glycol