Atropine Sulfate Rapidly-Disintegrating Sublingual Tablets

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Solution Overview

Problem

Current methods for administering atropine sulfate for organophosphate toxicity, such as intramuscular injections, are limited by size constraints, high costs, and the inability to self-administer effectively in emergency situations, leading to insufficient treatment and potential administration errors.

Innovation Solution

Development of rapidly-disintegrating sublingual tablets (RDSTs) containing atropine sulfate, formulated with microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate, which disintegrate in less than 30 seconds, allowing for rapid drug release and absorption, overcoming the limitations of traditional injection methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If intramuscular injections are used to administer atropine sulfate, then the drug can be delivered effectively, but the method is limited by size constraints, high costs, and inability to self-administer

Engineering Contradiction:
Improveself-administration capabilityVSAvoidinjection device requirements
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent transforms atropine sulfate from injection form to orally-disintegrating tablet form, changing the physical state and administration route parameters. This allows the drug to dissolve rapidly in the mouth and be absorbed through the buccal mucosa, enabling self-administration without needles or complex injection devices while maintaining therapeutic effectiveness

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the mechanical injection system (needles, syringes, auto-injectors) with a simple orally-disintegrating tablet that dissolves in saliva. This substitution eliminates the need for complex mechanical injection devices and enables patients to self-administer the medication easily

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If traditional injection methods are used, then drug delivery is reliable, but the cost and size constraints limit accessibility

Engineering Contradiction:
Improvedrug delivery effectivenessVSAvoidcost and accessibility
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs orally-disintegrating tablets as inexpensive, single-use dosage forms that eliminate the need for expensive, reusable injection equipment. Each tablet is a self-contained, disposable unit that dissolves rapidly in the mouth, providing reliable drug delivery at a fraction of the cost of auto-injectors or pre-filled syringes

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention extracts the active pharmaceutical ingredient (atropine sulfate) from the complex injection delivery system and delivers it through a simplified orally-disintegrating tablet format. This extraction removes the need for needles, syringes, and complex packaging while maintaining drug efficacy

Inventive Principle:
Principle #2Taking out (Extraction)

3Speed

If rapid disintegration is achieved, then drug absorption is faster, but formulation complexity increases

Engineering Contradiction:
Improvedisintegration rateVSAvoidformulation complexity
Core Design Contradiction:
SpeedVSDevice complexity

Solution Approach 1:

The patent utilizes porous superdisintegrants (such as croscarmellose sodium, sodium starch glycolate, or crosslinked polyvinyl pyrrolidone) within the tablet formulation. These porous materials rapidly absorb saliva and swell, causing the tablet to disintegrate within seconds in the oral cavity, enabling fast drug release and absorption through the buccal mucosa

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The invention employs composite tablet formulations combining atropine sulfate with multiple excipients including fillers, binders, lubricants, and superdisintegrants. This composite structure balances rapid disintegration with manufacturability, achieving disintegration in less than 30 seconds while maintaining straightforward manufacturing processes

Inventive Principle:
Principle #40Composite materials

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The RDSTs provide a convenient, cost-effective, and patient-friendly alternative for treating acute organophosphate toxicity, ensuring rapid drug absorption and effective symptom management without the need for healthcare settings.

Implementation Method 1

rapidly-disintegrating sublingual tablets (RDSTs) containing atropine sulfate, formulated with microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate, which disintegrate in less than 30 seconds

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 2

formulated with microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate, which disintegrate in less than 30 seconds, allowing for rapid drug release and absorption

Methodology Applied
Scientific EffectOsmotic pressure: Osmotic Pressure

Implementation Method 3

allowing for rapid drug release and absorption, overcoming the limitations of traditional injection methods

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Data Source

PatentEP3200793B1Atropine sulfate rapidly-disintegrating sublingual tablets, methods for manufacture, and methods for use thereof for treatment of acute organophosphate toxicity
Publication Date: 2019.08.28 NOVA SOUTHEASTERN UNIVERSITY
  • EP3200793B1 patent drawingFigure 1~2
  • EP3200793B1 patent drawingFigure 3a~4
  • EP3200793B1 patent drawingFigure 5

AI summary

The invention provides atropine sulfate (AS) rapidly-disintegrating sublingual tablets (RDSTs) in a sublingual dosage form and methods for therapeutic use of the AS RDSTs for treatment of organophosphate (OP) exposure and acute toxicity. The AS RDSTs provide an alternative easy-to-use dosage form for the management of organophosphate toxicity. Additionally, the invention provides methods for formulation and quality evaluation of the atropine sulfate rapidly-disintegrating sublingual tablets.