Drug transport from thin applications of topical dosage forms: development of methodology.
There are presently no standards for in vitro research dealing with the release and delivery of drugs from semisolid dosage forms, largely because of inherent experimental difficulties. Among the problems, it has proven difficult to apply dosage forms to membranes mounted in in vitro diffusion cells in facsimile to the manner in which the dosage forms are applied clinically. In the present studies, methodology has been developed which allows films with thicknesses approaching clinical dimensions to be spread evenly over silicone rubber membranes. Using methyl p-aminobenzoate as a test permeant and gelled water and water/propylene glycol solvent systems as test vehicles, it has proven possible to spread films as thin as 75 microns, yielding highly reproducible delivery profiles. Using this application technique, it has been shown how the diffusive clearance of drug from films of fixed composition placed over a resistant membrane is dependent on the thickness of application. For a given medium and thickness of application, when the vehicle composition is enriched in propylene glycol, partitioning into the membrane is suppressed, resulting in a lessening of the absolute rate of delivery and, consequently, a prolongation of the period over which drug is released. Increasing the membrane's resistance, i.e., increasing the membrane's thickness, likewise slows down the absolute delivery rate, extending the effective period of total clearance of drug from the applied film.
Addicks
W J
WJ
College of Pharmacy, University of Michigan, Ann Arbor 48109.
Flynn
G L
GL
Weiner
N
N
Chiang
C M
CM
D010129:4-Aminobenzoic Acid / Q000032:analysis; D000287:Administration, Topical; D002851:Chromatography, High Pressure Liquid; D005782:Gels; D008567:Membranes, Artificial; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility
D005782:Gels; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D010129:4-Aminobenzoic Acid