Effect of the Filler Grade on the Characteristics and the Sublingual Permeability of Atropine Sulfate Fast Disintegrating Sublingual Tablets.

Context: AS FDSTs will provide an accessible alternative for AS autoinjector (ATROPEN (R)), and a noninvasive first-aid antidote for the treatment of organophosphate (OP) poisoning and reduce the number of fatalities due to nerve gas attacks or OP pesticide poisoning. Objective: The effects of changing the filler grade on the characteristics of atropine sulfate (AS) fast disintegrating sublingual tablets (FDSTs) and AS sublingual permeability were investigated in order to optimize the formulation of AS FDSTs and, therefore, AS sublingual permeability. Methods: Two batches of AS FDSTs containing AS 8 mg were formulated and manufactured using two different filler grades: microcrystalline cellulose (MCC) UF-702 (formulation A) and MCC PH-301 (formulation B). Several United States Pharmacopeia (USP) and non-USP physical tests were performed to evaluate the AS FDSTs' characteristics. The AS permeability from the two AS FDST batches were evaluated using Franz cells through excised porcine sublingual membranes. Results were statistically compared at p < .05. Results: Both batches passed the content uniformity and friability tests. Formulation A tablets were significantly different from formulation A tablets and resulted in better powder flowability, higher breaking force, faster disintegration, faster dissolution rate, higher water uptake, and higher AS permeability. Conclusion: The selection of the filler grade to be used in the formulation of AS FDSTs can significantly impact their characteristics and significantly affect AS sublingual permeability, which can be used to improve the sublingual delivery of AS and the potential of using AS FDSTs as an alternative dosage form for the first-aid treatment of OP poisoning.