Stratum Corneum Sampling to Assess Bioequivalence between Topical Acyclovir Products

• Published in: Pharmaceutical research Vol. 36; no. 12; pp. 180 - 16
• Main Authors: Pensado, A., Chiu, W.S., Cordery, S. F., Rantou, E., Bunge, A. L., Delgado-Charro, M. B., Guy, R. H.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-12-2019; Springer; Springer Nature B.V
• Subjects: Acyclovir; Acyclovir - administration & dosage; Acyclovir - pharmacokinetics; Administration, Topical; Adult; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Antiviral drugs; Bioavailability; Biochemistry; Bioequivalence; Biological Availability; Biological Transport; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Drug Liberation; Female; Humans; Male; Medical Law; Middle Aged; Permeability; Pharmacology/Toxicology; Pharmacy; Research Paper; Sampling; Skin; Skin - metabolism; Skin Absorption; Skin Cream - administration & dosage; Skin Cream - pharmacokinetics; Stratum corneum; Therapeutic Equivalency; Topical bioequivalence: a case study with acicylovir cream; skin; stratum corneum sampling; topical bioequivalence; acyclovir; topical bioavailability; scaled average bioequivalence (SABE)
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-019-2707-3

Purpose
To examine the potential of stratum corneum (SC) sampling via tape-stripping in humans to assess bioequivalence of topical acyclovir drug products, and to explore the potential value of alternative metrics of local skin bioavailability calculable from SC sampling experiments.
Methods
Three acyclovir creams were considered in two separate studies in which drug amounts in the SC after uptake and clearance periods were measured and used to assess bioequivalence. In each study, a “reference” formulation (evaluated twice) was compared to the “test” in 10 subjects. Each application site was replicated to achieve greater statistical power with fewer volunteers.
Results
SC sampling revealed similarities and differences between products consistent with results from other surrogate bioequivalence measures, including dermal open-flow microperfusion experiments. Further analysis of the tape-stripping data permitted acyclovir flux into the viable skin to be deduced and drug concentration in that ‘compartment’ to be estimated.
Conclusions
Acyclovir quantities determined in the SC, following a single-time point uptake and clearance protocol, can be judiciously used both to objectively compare product performance in vivo and to assess delivery of the active into skin tissue below the barrier, thereby permitting local concentrations at or near to the site of action to be determined.