Use of an in vitro human skin permeation assay to assess bioequivalence of two topical cream formulations containing butenafine hydrochloride (1%, w/w).
The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream.
Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., West Point, PA 19486, USA. Electronic address: mitraamitava11@gmail.com.
Amitava
A
Mitra
Bayer Consumer Care, Memphis, TN 38112, USA.
Nanhye
N
Kim
Charles River Laboratories, Tranent, East Lothian, EH33 2NE, UK.
Darren
D
Spark
Charles River Laboratories, Tranent, East Lothian, EH33 2NE, UK.
Frank
F
Toner
Charles River Laboratories, Tranent, East Lothian, EH33 2NE, UK.
Susan
S
Craig
Charles River Laboratories, Tranent, East Lothian, EH33 2NE, UK.
Clive
C
Roper
Bayer Consumer Care, Memphis, TN 38112, USA. Electronic address: thomas.meyer3@bayer.com.
Thomas A
TA
Meyer
D000279:Administration, Cutaneous; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001596:Benzylamines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009281:Naphthalenes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D009824:Ointments; D010539:Permeability; D010865:Pilot Projects; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency
D000935:Antifungal Agents; D001596:Benzylamines; D005079:Excipients; D009281:Naphthalenes; D009824:Ointments; C067594:butenafine
Bioequivalence; Butenafine; Dermal; Flux; Skin permeation; Topical