Niclosamide Oral Formulation With Permeability Enhancers
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Solution Overview
Problem
There is a need for a safe and effective method to treat or prevent coronavirus infections, particularly those caused by SARS-CoV-2 and its variants, as existing antiviral drugs like niclosamide have low bioavailability due to low permeability and solubility, limiting their clinical application.
Innovation Solution
Compositions comprising niclosamide and permeability enhancers, such as fatty acids or surfactants, are developed to increase the transport of niclosamide across cell membranes, enhancing its bioavailability and efficacy in treating or preventing coronavirus infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If niclosamide is used as an antiviral drug, then it can treat or prevent coronavirus infections, but its low bioavailability due to low permeability and solubility limits its clinical application
Solution Approach 1:
The patent combines niclosamide with permeability enhancers (such as fatty acids, surfactants, or lipid-based carriers) to create a composite formulation. This composite approach allows the drug to maintain its antiviral efficacy while the permeability enhancer component addresses the low bioavailability issue by facilitating better absorption and transport across biological membranes.
Solution Approach 2:
The patent modifies the physical and chemical parameters of niclosamide by changing its formulation state (e.g., converting to salts, esters, or prodrugs) or by adjusting formulation parameters (pH, solubility, particle size) to enhance its permeability and bioavailability while maintaining its antiviral activity.
2Ease of operation
If niclosamide is administered orally, then it can be used for treatment, but its low permeability results in low systemic bioavailability
Solution Approach 1:
The patent introduces permeability enhancers as intermediary substances that facilitate the transport of niclosamide across the gastrointestinal tract and intestinal membranes. These intermediaries (such as surfactants or lipid carriers) act as mediators between the orally administered drug and the systemic circulation, enabling better absorption without requiring changes to the administration route.
3Reliability
If niclosamide is used at higher doses to overcome low bioavailability, then efficacy may improve, but side effects and toxicity increase
Solution Approach 1:
By changing the formulation parameters (using permeability enhancers, lipid carriers, or modifying the drug's physical state), the patent achieves better bioavailability at lower doses. This allows maintaining therapeutic efficacy while reducing the actual amount of drug that reaches systemic circulation, thereby minimizing side effects and toxicity.
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 significantly enhance niclosamide's bioavailability, allowing for effective treatment or prevention of coronavirus infections, including SARS-CoV-2 and its variants, by increasing permeability by up to 150% and improving oral absorption.
Implementation Method 1
The compositions can increase the amount of a niclosamide compound capable of being transported across a cell membrane
Data Source
AI summary
The present invention concerns compositions comprising at least one niclosamide compound, such as niclosamide or a pharmaceutically acceptable salt thereof, and at least one permeability enhancer, such as glycerol or dimethylpalmityl-ammonio propanesulfonate (PPS), and their use of such compositions as niclosamide agents. Advantageously, the niclosamide compound is capable of being transported across a Caco-2 cell membrane by at least 150% relative to the amount capable of being transported across the Caco-2 cell membrane in the absence of the permeability enhancer. Compositions, including oral dosage forms, and methods for delivering niclosamide compounds, such as for treatment or prevention of human coronavirus infections, are also provided.