Use of excised human skin to assess the bioequivalence of topical products.
BACKGROUND
Establishing the bioequivalence of topical drug products is a costly and time-consuming process since, with few exceptions, clinical efficacy trials are required.


OBJECTIVE
To develop a surrogate for clinical bioequivalence testing through evaluation of the kinetics of drug absorption in vitro through excised human skin.


METHODS
The percutaneous absorption of seven approved generic topical drug products was compared with their corresponding reference products during preclinical development using the Franz diffusion cell. Thereafter, following the conduct of bioequivalence trials and regulatory approval of these products in the United States, clinical data became available to which the in vitro data were compared.


RESULTS
In six of the seven cases the in vitro test:reference ratio for total absorption was close to one and indicated that the products were equivalent, in agreement with the clinical data. Results from the seventh case, in which the test:reference ratio was only 0.63, indicated that the in vitro model actually had greater sensitivity than the clinical method to detect small differences between products.


CONCLUSIONS
These data demonstrate the relevance and predictive power of the in vitro human skin model and strongly support its use as a surrogate for in vivo bioequivalence studies.
Franz
T J
TJ
Cetero Research, Fargo, North Dakota, USA. franzcell@verizon.net
Lehman
P A
PA
Raney
S G
SG
D000287:Administration, Topical; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D012189:Retrospective Studies; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology*; D013810:Therapeutic Equivalency
D004364:Pharmaceutical Preparations
J Pharm Sci. 1984 Sep;73(9):1255-8
6491945
J Invest Dermatol. 1987 Aug;89(2):142-6
3598206
Pharm Res. 2008 Jan;25(1):87-103
17985216
J Invest Dermatol. 1970 May;54(5):399-404
4245370
Br J Dermatol. 1986 Jul;115(1):1-11
3730275
Pharm Res. 2009 Feb;26(2):316-28
18941872
Int J Dermatol. 1999 Aug;38(8):628-32
10487457
Fundam Appl Toxicol. 1994 Aug;23(2):230-6
7982531
Pharm Res. 1998 Jun;15(6):877-82
9647353
Curr Probl Dermatol. 1978;7:58-68
752458
J Invest Dermatol. 1975 Mar;64(3):190-5
123263