In vitro-in vivo correlation study for the dermatopharmacokinetics of terbinafine hydrochloride topical cream.
BACKGROUND
To investigate the relationship between dermatopharmacokinetic (DPK) tape stripping from in vitro and in vivo using 1% terbinafine hydrochloride topical cream as the model formulation.


METHODS
In vitro and in vivo tape strippings were conducted on separated pig ear skin used as a biological membrane for franz diffusion cell testing and the non-hairy skin area at the ventral forearms of healthy volunteers, respectively. Terbinafine (1%) topical cream was applied to the skin for 0.5, 2, and 4 h. The drug profiles of terbinafine across the stratum corneum were determined immediately (time 0 h), and at 0.5, 1, 2, and 4 h after removing the formulation. The amounts of terbinafine were analyzed by a validated high-performance liquid chromatography-ultraviolet method. The area under the curve (AUC) and the maximum amounts of terbinafine absorption (Q(max)) were obtained from pharmacokinetic software. Partition coefficient (K(SC/veh)) and diffusion parameter (D/L²) were derived from the Fick's second law equation. During the schedule time of 8 h, the deviations of in vitro and in vivo data were 6.61 and 30.46% for AUC and Q(max), respectively. There was insignificant difference of the K(SC/veh) and the D/L² between excised pig ear and human skin. In addition, K(SC/veh) and D/L² at T(max) of 2 h were used to predict the AUC presented the value of 4.7481 %h whereas the true value calculated from pharmacokinetic software provided the value of 5.9311 %h differing from each other in approximate of 20%.


CONCLUSIONS
In vitro tape stripping using the separated pig ear skin as a viable membrane of the franz diffusion cell testing demonstrates the potential to represent in vivo tape stripping in human for topical bioavailability/bioequivalence study of terbinafine hydrochloride 1% topical cream.
Department of Pharmacy, Mahidol University, Bangkok, Thailand. pyksk2001@yahoo.com.sg
Suwadee
S
Saeheng
Wichit
W
Nosoongnoen
Supenya
S
Varothai
Korbtham
K
Sathirakul
D000328:Adult; D000465:Algorithms; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D055598:Chemical Phenomena; D020405:Dermis / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D006204:Hair Removal; D006801:Humans; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D063465:Skin Cream / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D053832:Surgical Tape; D034421:Sus scrofa; D000077291:Terbinafine; D055815:Young Adult
D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine