Methisoprinol Aqueous Injectable Composition Stability
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Solution Overview
Problem
Current formulations of Methisoprinol are unstable in aqueous solutions, leading to degradation and crystallization, which limits its use in injectable forms, particularly for human administration, due to poor solubility and susceptibility to oxidation, and existing compositions often include undesirable excipients like high amounts of sugar or alcohol that are not suitable for all patients.
Innovation Solution
A stable aqueous injectable composition of Methisoprinol is formulated with specific amounts of alcohol (20-40% w/v) and excipients like propylene glycol, glycerin, and monothioglycerol, which maintains stability and prevents crystallization, allowing for parenteral administration without the need for high sugar or alcohol content.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If Methisoprinol is formulated in aqueous solution, then it can be administered by injection, but it degrades and crystallizes during storage
Solution Approach 1:
The patent uses alcohols (ethanol, isopropanol, or a combination) as intermediary substances to stabilize Methisoprinol in aqueous injectable formulations. The alcohol acts as a mediator that prevents crystallization and degradation of Methisoprinol during storage, enabling both injectable administration and storage stability. The specific alcohol content is optimized to balance solubility, stability, and safety for different administration routes.
2Stability of the object's composition
If high alcohol content is used to prevent crystallization, then solubility improves, but the composition becomes unsuitable for intravenous administration
Solution Approach 1:
The patent optimizes the alcohol content parameter to different ranges based on the intended administration route. For intramuscular injection, higher alcohol content (20-40% w/v) is used to ensure stability and prevent crystallization. For intravenous administration, lower alcohol content (5-20% w/v) is specified to maintain safety while still preventing crystallization. This parameter optimization resolves the contradiction between stability and safety for different routes.
3Ease of operation
If sugar is added to mask bitter taste, then patient compliance improves, but it becomes unsuitable for diabetic patients
Solution Approach 1:
The patent removes sugar from the formulation entirely, extracting the problematic ingredient that caused the bitter taste issue. Instead of masking the bitter taste with sugar, the invention focuses on optimizing the formulation to eliminate the need for sugar, thereby making the composition suitable for diabetic patients while maintaining patient compliance through appropriate dosing and administration.
4Ease of operation
If oral dosage form is used, then patient comfort is maintained, but it takes time to reach required blood levels in acute conditions
Solution Approach 1:
The patent inverts the conventional approach by developing injectable formulations instead of oral formulations. The injectable form delivers Methisoprinol directly into the bloodstream or muscle tissue, bypassing the gastrointestinal absorption process. This inversion of administration route dramatically accelerates the time to reach therapeutic blood levels while maintaining patient comfort through less invasive administration compared to repeated oral dosing in acute conditions.
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 composition remains stable for extended periods, free from crystallization and degradation, and is suitable for multiple routes of administration, addressing the unmet need for a stable injectable form of Methisoprinol that meets regulatory guidelines and patient suitability.
Implementation Method 1
Poor aqueous solubility of Methisoprinol has a particularly high tendency to crystallize from aqueous and organic solutions. A stable aqueous injectable composition of Methisoprinol is formulated with specific amounts of alcohol (20-40% w/v) which maintains stability and prevents crystallization
Implementation Method 2
Methisoprinol as a drug... is susceptible to oxidation. A stable aqueous injectable composition of Methisoprinol is formulated with specific amounts of alcohol (20-40% w/v) and excipients like propylene glycol, glycerin, and monothioglycerol, which maintains stability and prevents crystallization
Data Source
AI summary
The present invention provides a stable aqueous composition of Methisoprinol. In particular, it provides a stable aqueous injectable composition comprising 25 to 150 mg/ml of Methisoprinol, at least one alcohol, and at least one excipient selected from pH modifier or buffer, surfactant, solvents, co-solvent, preservative, antioxidants, chelating agent and a tonicity modifier. The alcohol is present in proportion up to 40% w/v, preferably up to 30% w/v. The invention also provides methods of preparation of such composition and uses thereof in the treatment or prevention of viral diseases and immune suppressed states.