Student Theses, Dissertations and Capstones

Document Type


Degree Name

Doctor of Philosophy (PhD) in Pharmacy

Copyright Statement

All rights reserved. This publication is intended for use solely by faculty, students, and staff of Nova Southeastern University. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.


College of Pharmacy

First Advisor

Mutasem Rawas-Qalaji

Publication Date / Copyright Date



Nova Southeastern University


Atropine Sulfate (AS) auto-injector (AtroPen®) is being used as an effective and safe antidote for the treatment of organophosphate (OP) pesticides or nerve gas poisoning. The use of AtroPen® is associated with several drawbacks including: bulky size, availability, affordability, invasiveness, and administration errors. Previously, AS fast disintegrating sublingual tablets (FDSTs) were developed and the feasibility of AS sublingual permeability were demonstrated. However, AS permeability was delayed due to the negative impact of higher doses of AS on FDST’s physical characteristics. Therefore, the aim in this research project was to optimize the previously developed AS FDSTs. It was hypothesized that optimizing the tablet’s filler grade will improve the tablet physical characteristics along with incorporating a pH modifier and penetration enhancers will significantly enhance AS sublingual permeability. Ten batches of AS FDSTs containing AS 8 mg were manufactured using a highly compressible filler grade of microcrystalline cellulose, MCC UF-702. AS FDSTs with and without a pH modifier (Na Bicarb 2%), or penetration enhancers (sodium dodecyl sulfate (SDS 0.5% or 1%), palmitoyl carnitine chloride (PCC 16%), or sodium glycocholate (Na Gly 15% or 20%)) were manufactured and evaluated. Several US Pharmacopeia (USP) and non-USP physical tests were performed to evaluate AS FDSTs’ characteristics. AS permeability from the ten AS FDST formulations were evaluated using Franz cells through excised porcine sublingual membranes. Results were statistically compared and deemed significant if p< 0.05. All manufactured AS FDSTs passed the quality control tests. MCC UF-702 grade resulted in better powder flowability, higher breaking force, faster disintegration, faster dissolution rate, and higher water uptake. AS sublingual permeability was linear, indicating for a passive transport. Transcellular enhancers had significantly higher AS permeability enhancement in comparison to paracellular enhancer. Incorporating Na Bicarb 2% along with SDS 1% into AS FDSTs resulted in the highest enhancement in AS cumulative sublingual permeation (AUC0-90 min), influx, and permeability. These optimized novel AS FDSTs has the potential to deliver therapeutic AS concentrations to the systemic circulation and achieve rapid onset of action for the first-aid treatment of OP toxicity. Further pharmacokinetics studies are recommended to determine the bioequivalence sublingual AS dose to AtroPen®.


Pharmacy and Pharmaceutical Sciences


Atropine sulfate, Fast disintegrating tablet, Organophosphates, Permeability, Sublingual



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