Lyophilised reservoirs in combination with hydrogel-forming microarray patches for transdermal delivery of isoniazid and pyridoxine hydrochloride

Abstract

Tuberculosis remains a major global health concern, presenting as either active disease or latent infection, the latter carrying a risk of activation, particularly in immunocompromised individuals. Prolonged isoniazid monotherapy is the standard preventive treatment, often supplemented with pyridoxine to mitigate isoniazid-induced pyridoxine depletion, as recommended by the US Centers for Disease Control and Prevention. This present study investigates an alternative transdermal approach using hydrogel-forming microarray patches (MAPs) incorporating lyophilised isoniazid and pyridoxine wafers. The MAPs were formulated with a novel poly(vinylpyrrolidone) and poly(vinyl alcohol) hydrogel, supplemented with sorbitol and adipic acid. In vitro studies demonstrated that approximately 15 % of isoniazid (8 mg) and 10 % of pyridoxine HCl (5 mg) permeated neonatal porcine skin over 24 h. In Sprague Dawley rats, MAPs provided significantly greater systemic exposure to isoniazid compared to oral administration (11,485 ± 1297 ng·mL^-1·day vs. 9538 ± 656 ng·mL^-1·day). A similar trend was observed for pyridoxine HCl, with MAPs yielding higher systemic exposure than the oral control (6118 ± 1185 ng·mL^-1·day vs. 823 ± 322 ng·mL^-1·day). These findings suggest that hydrogel-forming MAPs, which bypass first-pass metabolism and reduce hepatic exposure, hold promise as an effective alternative for the long-term management of latent tuberculosis.

Keywords: Hydrogel-forming microarray patches; Isoniazid; Latent tuberculosis; Microneedles; Pyridoxine HCl.