A new discriminative criterion for the development of Franz diffusion tests for transdermal pharmaceuticals.
OBJECTIVE
In vitro skin/membrane permeation profiling of topical pharmaceuticals is an important overall quality attribute in the evaluation of product consistency and it is also used for IVIVR (in vitro - in vivo relationship) purposes in product development and change control. Franz diffusion cell (FDC) experiments are emerging as a generally accepted methodology in this field, where the choice of operational conditions requires a data-supported justification towards the discriminating power of the test. A response function is therefore proposed to objectively quantify the discriminating power.


METHODS
We evaluated the usefulness of the proposed response function by studying one of the operational conditions, i.e. the influence of receptor medium composition, on the FDC in vitro penetration behaviour of the model compound testosterone formulated in four different topical preparations, using both artificial membranes and dermatomed human skin.


RESULTS
From the obtained cumulative amount of testosterone in the receptor fluid versus time curves, the permeability coefficient Kp of testosterone from each formulation was calculated. The evaluation of the discriminating power of the different media was performed using our new objective response function based upon an equal spread criterion of normalised Kp values.


CONCLUSIONS
We demonstrated significant differences in discriminating power between the different media used, with the overall best results obtained with hydroxypropyl-beta-cyclodextrine (HPBCD) containing media. The proposed new criterion was found to be useful for the rational design of an in vitro diffusion test for transdermal pharmaceuticals.
Baert
Bram
B
Drug Quality and Registration group, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium.
Boonen
Jente
J
Burvenich
Christian
C
Roche
Nathalie
N
Stillaert
Filip
F
Blondeel
Phillip
P
Van Boxclaer
Jan
J
De Spiegeleer
Bart
B
D000279:Administration, Cutaneous; D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000728:Androgens / Q000008:administration & dosage / Q000493:pharmacokinetics; D004058:Diffusion; D000431:Ethanol / Q000737:chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D008954:Models, Biological; D010539:Permeability; D053284:Polyunsaturated Alkamides; D012869:Skin Absorption; D012965:Sodium Chloride / Q000737:chemistry; D013739:Testosterone / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000577:Amides; D000728:Androgens; C489347:N-isobutyl-2E-decenamide; D053284:Polyunsaturated Alkamides; D000431:Ethanol; D013739:Testosterone; D012965:Sodium Chloride