SARM Solid Polymorphs for Bioavailability and Stability
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Solution Overview
Problem
Current approaches lack effective solutions for developing compounds useful in male contraception, treating hormone-related conditions such as Androgen Decline in Aging Male (ADAM) and Androgen Decline in Female (ADIF), chronic muscular wasting, and prostate cancer, with limitations in bioavailability and stability of pharmaceutical forms.
Innovation Solution
Development of solid forms of (R) or (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide, which act as selective androgen receptor modulators (SARMs), including crystalline and paracrystalline forms, for enhanced androgenic and anabolic activity, and processes for their preparation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional pharmaceutical forms are used, then ease of manufacture is maintained, but bioavailability and stability are insufficient
Solution Approach 1:
The patent applies parameter changes by developing multiple polymorphic forms (Forms I, II, III, IV) of the SARM compound, each with distinct crystal structures and physical properties. These different solid forms exhibit varying degrees of bioavailability and stability, allowing optimization of pharmaceutical performance through selection of appropriate polymorphic forms rather than changing the chemical structure itself.
Solution Approach 2:
The patent employs composite materials by creating pharmaceutical compositions that combine the SARM compound in specific polymorphic forms with excipients and carriers. This approach enhances both bioavailability and stability while maintaining ease of manufacture through standard pharmaceutical formulation techniques.
2Stability of the object's composition
If conventional pharmaceutical forms are used, then ease of manufacture is maintained, but stability is insufficient
Solution Approach 1:
The patent utilizes parameter changes by identifying and characterizing multiple polymorphic forms with different stability profiles. Form I, for example, is described as having improved stability compared to other forms. The ability to select and control which polymorphic form is produced allows optimization of stability while using conventional manufacturing processes.
Solution Approach 2:
The patent applies preliminary action by establishing specific crystallization conditions and processing parameters that preferentially produce the desired stable polymorphic form during manufacturing. This pre-control of crystal formation ensures stability is built into the product during synthesis rather than requiring post-processing stabilization.
3Reliability
If different polymorphic forms are developed, then bioavailability is improved, but device complexity increases
Solution Approach 1:
The patent resolves this contradiction by using parameter changes in the form of different polymorphic structures (Forms I, II, III, IV) that can be obtained through variations in crystallization conditions, solvents, and processing parameters. Each form offers different bioavailability characteristics, allowing optimization without requiring complex delivery devices or administration systems.
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 solid forms demonstrate improved bioavailability and stability, making them effective for male contraception, treating hormone-related conditions, and managing prostate cancer, with specific polymorphic forms optimizing pharmacokinetic properties.
Implementation Method 1
Development of solid forms of (R) or (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide, which act as selective androgen receptor modulators (SARMs), including crystalline and paracrystalline forms
Data Source
AI summary
The present invention relates to solid forms of (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide and processes for producing the same.