Lorazepam Eutectic Mixture Transmucosal Delivery
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Solution Overview
Problem
Current benzodiazepine formulations, particularly Lorazepam, face challenges due to low solubility in water and instability when administered intranasally or buccally, leading to slow absorption and irritation, making it difficult to achieve effective anticonvulsant action in emergency seizure situations.
Innovation Solution
The development of Lorazepam eutectic mixtures with organic molecules like menthol and thymol, combined with a hydrophobic phase and surfactants, enhances oil solubility and stability, allowing for fast and effective intraoral transmucosal delivery via self-emulsifying compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If intranasal administration of Lorazepam is used, then convenience of administration is improved, but solubility and stability are worsened due to low water solubility
Solution Approach 1:
The patent changes the physical-chemical parameters of the formulation by using self-emulsifying compositions that transform from oil phase to fine emulsion droplets upon contact with aqueous media, enabling Lorazepam to achieve adequate solubility and stability for intranasal administration without compromising the active ingredient
Solution Approach 2:
The patent employs composite material systems combining hydrophobic oil phase with surfactants and co-surfactants to create self-emulsifying formulations that provide both solubility enhancement and stability, allowing Lorazepam to be effectively delivered via intranasal route
2Speed
If traditional parenteral dosage forms are used, then rapid clinical response is achieved, but ease of administration is worsened in out of hospital settings
Solution Approach 1:
The patent introduces self-emulsifying compositions as an intermediary system that bridges the gap between oral and parenteral administration, providing rapid absorption comparable to parenteral routes while maintaining the ease of non-invasive administration suitable for out-of-hospital settings
3Quantity of substance
If larger volume is administered intranasally, then adequate dose is achieved, but swallowing occurs which delays absorption
Solution Approach 1:
The patent changes the physical state and emulsion properties of the formulation to optimize the balance between administerable volume and absorption efficiency, ensuring adequate dosing while minimizing swallowing through improved emulsion characteristics
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
This approach provides a fast onset of anticonvulsant action comparable to parenteral administration, with improved solubility and stability, enabling effective seizure suppression and prolonged protection against seizures.
Implementation Method 1
The development of Lorazepam eutectic mixtures with organic molecules like menthol and thymol, combined with a hydrophobic phase and surfactants, enhances oil solubility and stability
Implementation Method 2
allowing for fast and effective intraoral transmucosal delivery via self-emulsifying compositions
Data Source
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AI summary
The current application relates to a liquid pharmaceutical composition for intraoral transmucosal administration of a benzodiazepine drug to a mammal. The composition comprises a physiologically acceptable hydrophobic phase, an eutectic mixture of benzodiazepine compound providing high solubility of the benzodiazepine in said hydrophobic phase, at least one physiologically acceptable organic solvent and at least one physiologically acceptable surfactant.