Tizoxanide Choline Salt for Improved Oral Bioavailability
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Solution Overview
Problem
Nitazoxanide exhibits low solubility in water, requires large dosages, and has low oral bioavailability, limiting its effectiveness in treating respiratory virus infections due to inadequate concentration in the lung.
Innovation Solution
A pharmaceutical composition comprising tizoxanide and choline hydroxide, formulated as a salt with a molar ratio of 1:1, which significantly improves solubility and bioavailability, and is administered in various forms such as capsules, tablets, or solutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If nitazoxanide is administered orally, then it can be given conveniently, but its low solubility and low oral bioavailability result in inadequate therapeutic concentration in the lung
Solution Approach 1:
The patent changes the chemical parameter of nitazoxanide by converting it to its active metabolite form, tizoxanide, and further modifying it as a prodrug candidate. This parameter change (molecular structure modification) directly addresses the solubility and bioavailability issues while maintaining the convenient oral administration route.
Solution Approach 2:
The patent introduces an intermediary approach by using tizoxanide as the active metabolite and developing prodrug candidates that can be converted to tizoxanide in vivo. This intermediary form serves as a bridge between the parent drug nitazoxanide and the desired therapeutic effect, improving solubility and bioavailability while maintaining ease of oral administration.
2Quantity of substance
If large dosage of nitazoxanide is used, then it may achieve therapeutic effect, but the low solubility limits the achievable concentration in the body
Solution Approach 1:
The patent applies parameter changes by modifying the molecular structure from nitazoxanide to tizoxanide and its prodrug candidates. This structural modification fundamentally changes the solubility parameter, allowing adequate therapeutic concentrations to be achieved without requiring excessively large dosages that would be limited by the original poor solubility.
3Adaptability or versatility
If nitazoxanide is used for new pharmacological actions, then broad-spectrum activity is achieved, but the clinical efficacy needs to be improved due to pharmacokinetic limitations
Solution Approach 1:
The patent uses tizoxanide as an intermediary active metabolite that retains the broad-spectrum antiviral, antibacterial, and antiparasitic activities of nitazoxanide. By developing prodrug candidates that convert to tizoxanide, the patent maintains the versatile broad-spectrum activity while improving the pharmacokinetic properties to achieve reliable clinical efficacy.
Solution Approach 2:
The patent applies parameter changes by modifying the molecular structure to improve pharmacokinetic parameters (solubility, bioavailability, tissue penetration) while preserving the pharmacodynamic properties that confer broad-spectrum activity. This allows the drug to maintain adaptability to different pathogens while achieving reliable clinical efficacy.
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 tizoxanide choline salt enhances solubility and bioavailability, allowing effective treatment of viral, bacterial, parasitic, and fibrotic diseases, including hepatitis, influenza, and cancer, by achieving therapeutic concentrations in the body.
Implementation Method 1
tizoxanide and choline hydroxide form a salt in a molar ratio of 1:1
Data Source
AI summary
A pharmaceutical composition contains tizoxanide and choline hydroxide, a choline salt of tizoxanide and crystal form thereof. A mixture of tizoxanide and choline hydroxide, or a salt thereof and crystal form of the salt significantly improve the solubility and bioavailability of tizoxanide, and exhibits favorable effects in drugs for treating viruses, fibrosis, bacteria, tumors and intestinal parasites.