Imaging mass spectrometry dermatology

Pharmacokinetics and Skin Tolerability of Intracutaneous Zolmitriptan Delivery in Swine Using Adhesive Dermally Applied Microarray

Joe Nguyen (1), Hayley Lewis (1), Ashley Queja (1), Anh Ngoc Diep (2), Guillaume Hochart (3), Mahmoud Ameri (3)

1) Zosano Pharma, 34790 Ardentech Court, Fremont, California 94555
2) Pathology Research Laboratory, 521 Rocca Avenue, South San Francisco, California 94080
3) ImaBiotech SAS, Parc Eurasanté, 885 Av. Eugène Avinée, 59120 Loos, France

Journal of Pharmaceutical Sciences, Volume 107, August 2018

Abstract
Adhesive Dermally Applied Microarray (ADAM) is a new drug-delivery system that uses microprojections (340-μm long) for intracutaneous drug self-administration. We formulated zolmitriptan, a well-accepted and commonly used migraine medication, for administration using ADAM. In vivo studies were conducted in female prepubescent Yorkshire pigs using ADAM 1.9-mg zolmitriptan applied to the inner thigh and left in place for 1 h. Pharmacokinetic studies showed that the ADAM 1.9-mg zolmitriptan was delivered with high efficiency (85%) and high absolute bioavailability (77%). Furthermore, in vivo evaluation showed a rapid systemic absorption with a median Tmax of 15 min. Skin biopsies of the treatment sites showed a mean depth of microprojection penetration of 105.4 ± 3.6 μm. Mass spectrometry imaging showed that the zolmitriptan after 1 h of patch wear time was predominantly localized to the dermis. ADAM zolmitriptan was well tolerated with a transient mild-to-moderate erythema response. The findings in these studies, particularly the rapid zolmitriptan absorption profile after intracutaneous administration, provided validation to advance ADAM zolmitriptan development.

Keywords
skin, absorption, pharmacokinetics, transdermal, bioavailability, dissolution, diffusion, formulation, first-pass metabolism, mass spectrometry

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