Molnupiravir Crystalline and Amorphous Forms
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Solution Overview
Problem
There is no existing publication that discloses the crystalline and amorphous forms of Molnupiravir, which are crucial for stability and pharmacological effectiveness, particularly in treating COVID-19 and other viral diseases.
Innovation Solution
The development of methods to prepare crystalline and amorphous forms of Molnupiravir, involving dissolution in solvents, optional treatment with carbon, addition of secondary solvents, cooling, and filtration or distillation to obtain pure forms, with specific XRPD patterns and high purity, suitable for pharmaceutical compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional synthesis methods are used to produce Molnupiravir, then the compound can be obtained, but the stability and pharmacological effectiveness are insufficient due to lack of defined crystalline or amorphous forms
Solution Approach 1:
The patent applies parameter changes by systematically varying solvent types (isopropyl alcohol, ethyl acetate, methyl tert-butyl ether, hexane), temperatures (50-85°C dissolution, 25-30°C cooling), and processing conditions to obtain different crystalline forms with distinct XRPD patterns. This resolves the contradiction by finding optimal parameters that achieve both stability (through defined crystal structures) and manufacturability (through straightforward dissolution-crystallization processes)
Solution Approach 2:
The patent utilizes phase transitions by dissolving Molnupiravir in hot solvents and then cooling to induce crystallization. The transition from dissolved state to crystalline state (or amorphous state via spray drying/lyophilization) provides the stability benefits of defined solid forms while maintaining ease of manufacture through simple temperature-controlled processes
2Manufacturing precision
If no specific crystalline or amorphous form is defined, then the manufacturing process is simpler, but the pharmacological effectiveness and stability are compromised
Solution Approach 1:
The patent applies preliminary action by incorporating optional carbon treatment steps before crystallization to pre-remove impurities. This preliminary purification action enables the subsequent crystallization process to produce high purity crystalline forms with defined XRPD patterns, resolving the contradiction between manufacturing precision and process complexity
3Stability of the object's composition
If crystalline forms are developed for Molnupiravir, then stability and pharmacological effect are improved, but the process complexity increases
Solution Approach 1:
The patent applies self-service by designing a process where Molnupiravir automatically crystallizes in defined forms when dissolved in specific solvents at controlled temperatures and then cooled. The compound essentially self-organizes into stable crystalline structures with characteristic XRPD patterns without requiring complex intervention, resolving the contradiction between stability improvement and operational simplicity
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 crystalline and amorphous forms exhibit remarkable stability, low hygroscopicity, and high purity, making them effective as active ingredients for preventing or treating COVID-19 and other viral diseases, with potential for mass production and commercial use.
Implementation Method 1
Molnupiravir is dissolved in a solvent at 50-85° C., cooling the mixture to 25-30° C., and filtering the precipitated solid to obtain pure crystalline form
Implementation Method 2
optionally treating the above solution in step-a) with carbon
Implementation Method 3
distilled out the solvent obtained in step-a) or step-b), and isolate the pure amorphous form of Molnupiravir
Implementation Method 4
The crystalline and amorphous forms exhibit remarkable stability, low hygroscopicity, and high purity
Data Source
AI summary
The present invention provides a crystalline and an amorphous form of a Molnupiravir and methods of making the crystalline form and amorphous form of Molnupiravir.