Citation

Rawas-Qalaji M, Bafail R, Saad Ahmed I, Nasir Uddin M, Nazzal S. Int. J. Pharm. 2021; ePub(ePub): ePub.

Copyright

(Copyright © 2021, Elsevier Publishing)

DOI

10.1016/j.ijpharm.2021.120898

PMID

unavailable

Abstract

Atropine sulfate (AS) auto-injectors are the only approved antidote for out-of-hospital emergency treatment of organophosphates (OP) toxicity. However, they are only available for military use and require the administration of multiple auto-injectors. Therefore, an alternative, patient-friendly and more affordable fast-disintegrating sublingual tablets (FDSTs) of AS were previously developed. In this article, the effect of modifying the microenvironment's pH and/or using penetration enhancers on AS sublingual transport pathways were evaluated in an attempt to further enhance AS sublingual permeability. Ten different AS FDST formulations with or without the incorporation of alkalizer and various penetration enhancers were manufactured and characterized. AS permeability was investigated through excised porcine sublingual membrane using Franz cells.

RESULTS showed that the incorporation of either a transcellular enhancer or alkalizer achieved a significantly higher AS permeability enhancement (twofold). Combining sodium bicarbonate (Na Bicarb) 2% as alkalizer with sodium dodecyl sulfate (SDS) 1% as a transcellular enhancer resulted in the greatest synergistic enhancement in AS sublingual permeability (up to twelvefold). In conclusion, the modified AS FDST developed in this work has the potential to improve the pharmacokinetic parameters of AS following sublingual administration for the first-aid treatment of OP toxicity in future animal bioequivalency studies.

Language: en

Keywords

AtroPen; Atropine Sulfate; Fast Disintegrating Tablet; Organophosphates; Permeability; Sublingual