Niclosamide Amorphous Solid Dispersion for Inhalation
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Solution Overview
Problem
Current formulations of niclosamide suffer from low solubility and are not suitable for inhalation delivery to the lungs, limiting its effectiveness in treating respiratory infections such as COVID-19, which targets ACE2 receptors in lungs, intestine, and blood vessels, particularly in populations with diabetes and hypertension.
Innovation Solution
Development of pharmaceutical compositions comprising niclosamide in an amorphous form as an amorphous solid dispersion, formulated through hot melt extrusion with pharmaceutically acceptable polymers like Kollidon VA64, and micronized for inhalation, ensuring higher drug loading and effective delivery to target organs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If niclosamide is formulated in conventional crystalline form, then the formulation is simple to manufacture, but the solubility and bioavailability are low
Solution Approach 1:
The patent transforms niclosamide from crystalline to amorphous form, changing the physical state parameter to improve solubility and bioavailability while maintaining manufacturability through hot melt extrusion processing
Solution Approach 2:
The patent creates composite amorphous solid dispersions by combining niclosamide with pharmaceutically acceptable polymers (such as hydroxypropyl cellulose, polyvinylpyrrolidone, or polyethylene glycol), where the polymer matrix stabilizes the amorphous drug form and enhances solubility
2Reliability
If niclosamide is formulated for inhalation delivery, then the effectiveness for respiratory infections is improved, but the formulation complexity increases
Solution Approach 1:
The patent formulates niclosamide as micronized particles with specific size ranges (0.5-5 μm for deep lung deposition, or 1-10 μm for general inhalation), segmenting the drug into respirable particle sizes that can be delivered through inhalation devices
Solution Approach 2:
The patent modifies particle size parameters and physical form (amorphous solid dispersion) to enable inhalation delivery, transforming the drug into a form suitable for respiratory administration while maintaining therapeutic efficacy
3Ease of operation
If niclosamide is administered orally in conventional form, then the administration route is simple, but the drug loading and delivery efficiency to target organs are low
Solution Approach 1:
The patent changes the physical and chemical parameters of niclosamide by converting it to amorphous form and creating solid dispersions, which dramatically improve solubility, dissolution rate, and consequently delivery efficiency to gastrointestinal and systemic targets
Solution Approach 2:
The patent uses polymer-drug composite systems where the pharmaceutically acceptable polymer enhances the oral bioavailability of niclosamide, enabling more efficient delivery to gastrointestinal ACE2 receptors and systemic circulation
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 compositions provide enhanced bioavailability and effective delivery of niclosamide to the lungs and gastrointestinal tract, potentially offering a therapeutic option for COVID-19 and other indications by maintaining a therapeutically effective dose and improving solubility and absorption.
Implementation Method 1
pharmaceutical compositions comprising niclosamide in an amorphous form as an amorphous solid dispersion
Implementation Method 2
formulated through hot melt extrusion with pharmaceutically acceptable polymers
Implementation Method 3
Niclosamide is well known for its protonophoric activity, in other words, the capability of transporting protons through membranes and disrupting pH gradients
Implementation Method 4
formulated for administration via inhalation... effective delivery of niclosamide to the lungs
Data Source
AI summary
The present disclosure provides pharmaceutical compositions of niclosamide that may be administered either orally or by inhalation. These compositions may allow the achievement of a therapeutically effective dose of niclosamide to the lungs or the gastrointestinal tract. These compositions may be used to treat one or more diseases or disorders such as a viral infection or cancer.