Variables Affecting Delivery of Glycopyrronium Tosylate Through Human Skin In Vitro

Hyperhidrosis is a condition of excessive sweating beyond what is physiologically required to maintain normal thermal regulation. Hyperhidrosis affects an estimated 4.8% of the US population, which amounts to approximately 15.3 million people.^1,2 The adverse impact of hyperhidrosis on quality of life has been well documented,^2,3 and a recent case-control study found that anxiety and depression are >3.5 times more prevalent among patients with hyperhidrosis than those without.⁴ Hyperhidrosis treatments may work to block sweat from reaching the skin surface (eg, topical antiperspirants), inhibit neuronal transduction to sweat glands (eg, injectable onabotulinumtoxinA or off-label use of oral anticholinergic drugs), destroy the sweat glands (eg, thermal ablation or surgical removal), or via unknown mechanisms (eg, iontophoresis).^2,5,6 These treatments vary greatly with respect to effectiveness, invasiveness, and side effects, and only three of these treatments are approved by the U.S. Food and Drug Administration (FDA) for axillary hyperhidrosis, including topical aluminum salts, onabotulinumtoxinA injections, and a microwave device for thermal ablation of sweat glands. Recently, glycopyrronium tosylate (GT), an acetylcholine receptor antagonist, was approved by the U.S. FDA in 2018 as a novel, once daily topical treatment for primary axillary hyperhidrosis in patients 9 years of age and older (QBREXZA^® [glycopyrronium] cloth, 2.4%, for topical use). Primary hyperhidrosis (excessive sweating without a known cause) is localized (focal), characteristically symmetric, and can affect the axillae, palms of the hands, soles of the feet, face, and other areas. Skin in other anatomical areas may be different from the axilla and therefore more studies are needed.

In the present studies, delivery of GT through skin from various anatomical sites, including the axillae, abdomen, palms, and soles, was investigated.The effect of occlusion was investigated as a means to increase delivery. Finally, the effect of exposure time (with and without occlusion) was investigated. GT was removed from the skin 5, 15, and 60 minutes after application.

Analytical Method
A liquid chromatography with tandem mass spectrometry (LC/ MS/MS) detection method was developed for the quantification of GT from the samples generated in this study. Briefly, the concentrations of GT were measured using an ultra- performance liquid chromatographic system (Nexera X2 Series UHPLC, Shimadzu) equipped with a triple quadrupole tandem