title: Formulation and Evaluation of Fast-Disintegrating Sublingual Tablets of Atropine Sulfate: the Effect of Tablet Dimensions and Drug Load on Tablet Characteristics.
abstract: In this study, we formulated and evaluated the effects of tablet dimensions and drug load on the characteristics of atropine sulfate (AS) fast-disintegrating sublingual tablets (FDSTs). We aim to develop AS FDSTs as an alternative non-invasive and portable dosage form for the emergency treatment of organophosphate (OP) toxicity. AS autoinjector, AtroPen®, is the only self-administered dosage form available as an antidote for-out-of-hospital emergency use, but it is associated with several limitations and drawbacks. Seven FDST formulations of two tablet sizes, 150 mg (A) and 50 mg (B), and of several AS loads, 0 mg (A1, B1), 2 mg (A2, B2), 4 mg (B3), and 8 mg (B4a, B4b), were formulated and manufactured by direct compression. AS FDST characteristics were evaluated using USP and non-USP tests. Results were statistically compared at p < 0.05. All FDSTs passed the USP content uniformity and friability tests, disintegrated and released AS in ≤30 and 60 s. B1 and B2 were significantly harder than A1 and A2. Water uptake of A1 was significantly the highest. However, B1 and B2 had shorter disintegration and wetting times and higher amounts of AS dissolved than did A1 and A2 (p < 0.05). Increasing AS negatively affected FDST tensile strength (p < 0.05 for B4a) and water uptake (p < 0.05 for B3, B4a and B4b), however, without affecting AS dissolution. Formulation of AS up to 16% into smaller FDSTs was successful. Smaller FDSTs were harder and disintegrated more quickly. These AS FDSTS have the potential for further in vivo testing to evaluate their OP antidote potential.
authors.affiliation: Department of Pharmaceutical Sciences, Health Professions Division, Nova Southeastern University, Fort Lauderdale, Florida, USA.
authors.forename: Alhussain
authors.initials: A
authors.lastname: Aodah
authors.affiliation: Department of Pharmaceutical Sciences, Health Professions Division, Nova Southeastern University, Fort Lauderdale, Florida, USA.
authors.forename: Rawan S
authors.initials: RS
authors.lastname: Bafail
authors.affiliation: Department of Pharmaceutical Sciences, Health Professions Division, Nova Southeastern University, Fort Lauderdale, Florida, USA. mr.qalaji@nova.edu.|College of Pharmacy, Health Professions Division, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, Florida, 33328, USA. mr.qalaji@nova.edu.
authors.forename: Mutasem
authors.initials: M
authors.lastname: Rawas-Qalaji
mesh_terms: D000286:Administration, Sublingual; D001285:Atropine / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods; D006244:Hardness; D006801:Humans; D062025:Organophosphate Poisoning / Q000188:drug therapy*; D010276:Parasympatholytics / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013607:Tablets; D017155:Wettability
chemical_list: D010276:Parasympatholytics; D013607:Tablets; D001285:Atropine
keywords: AtroPen; atropine; organophosphates; pesticides; rapidly disintegrating tablets