Transbuccal Delivery of Isoniazid: Ex Vivo Permeability and Drug-Surfactant Interaction Studies
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Research Article Transbuccal Delivery of Isoniazid: Ex Vivo Permeability and Drug-Surfactant Interaction Studies Roselene Kroth,1 Débora Fretes Argenta,1 Julia Conte,1 Beatriz Ribeiro Amaral,1 and Thiago Caon1,2
Received 2 June 2020; accepted 22 September 2020 Abstract. The oral administration of isoniazid (INH) may lead to discontinuation of tuberculosis treatment due to drug-related hepatotoxicity events, and thus, the transbuccal delivery of this drug was investigated, for the first time, as an alternative administration route. Ex vivo permeability assays were performed in Franz-type diffusion chambers, applying INH alone and in combination with sodium dodecyl sulfate (SDS) and sodium taurocholate (ST). After confirming the formation of micelle structures by dynamic light scattering analysis, UV-visible spectroscopy and zeta potential analyses were used to investigate drug-micelle interactions. In zeta potential analyses, no electrostatical interactions were identified for both surfactants in saliva buffer pH 6.8. Spectrophotometric analyses, in turn, indicated chemical interactions between INH and SDS in both pH values (2.0 and 6.8) whereas no interaction between the drug and ST was observed. Despite the interaction between SDS and drug, this surfactant increased the buccal transport rate of INH by approximately 11 times when compared with the control. In contrast, ST did not increase the drug permeability. The INH retention in SDS-treated mucosa was significantly higher when compared with the control and an effect on intercellular lipids was suggested. In vivo studies are needed to confirm the high INH absorption found here. KEY WORDS: buccal permeability; isoniazid; absorption enhancers; surfactants, micelle structures.
INTRODUCTION Tuberculosis (TB) is one of the top 10 causes of death globally and is the leading cause of death from a single infectious disease agent (1). In 2017, TB caused an estimated 1.3 million deaths among HIV-negative individuals and there were additional 300,000 deaths from TB among HIV-positive individuals (2). Most of these deaths could be averted with earlier diagnosis and treatment. Currently, uncomplicated pulmonary TB patients are treated considering a 6-month regimen, i.e., 2 months of daily isoniazid, rifampicin, pyrazinamide, and ethambutol followed by 4 months of daily isoniazid and rifampicin therapy (3). Although new drugs are being developed to face the challenge of emerging multidrug-resistant strains of Mycobacterium tuberculosis, isoniazid (INH) remains as a widely used and effective first-line agent. In addition to its high bactericidal potency, INH administered orally is almost completely absorbed from the gastrointestinal tract and 1
Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC 88040-900, Brazil. 2 To whom correspondence should be addressed. (e–mail: [email protected])
penetrates all body fluid cavities. The drug levels achieved in these regions are similar to serum levels (4). INH ac
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