Vericiguat Crystalline Forms for Stability and Bioavailability
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Solution Overview
Problem
There is a need for additional solid state forms of Vericiguat, including solvated forms, to improve processing properties, stability, and bioavailability, which are not adequately addressed by existing forms.
Innovation Solution
The development of crystalline polymorphs and salts of Vericiguat, particularly Vericiguat hydrochloride, with specific preparation processes, to enhance properties such as chemical stability, solubility, and handling characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing solid state forms of Vericiguat are used, then the basic pharmaceutical function is achieved, but processing properties and stability are inadequate
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing different polymorphic forms of Vericiguat, each with distinct crystal structures and physical properties. By changing the solid state form parameter from one polymorph to another, the invention achieves improved processing properties and stability simultaneously. Specifically, certain polymorphic forms exhibit better flowability, compressibility, and thermal stability, directly resolving the contradiction between ease of manufacture and reliability.
Solution Approach 2:
The patent employs phase transitions by converting Vericiguat between different solid state forms (polymorphs) through controlled crystallization processes. By inducing specific phase transitions during manufacturing, the invention optimizes both processing characteristics and final product stability. The ability to transition between polymorphic forms allows selection of the most suitable form for specific manufacturing operations while ensuring long-term stability.
2Productivity
If existing solid state forms of Vericiguat are used, then the pharmaceutical activity is maintained, but dissolution profile and bioavailability are not optimized
Solution Approach 1:
The patent utilizes parameter changes by selecting specific polymorphic forms of Vericiguat that exhibit superior dissolution characteristics. Different polymorphs have varying solubility and dissolution rates, and the invention identifies and applies the forms that optimize bioavailability while maintaining pharmaceutical activity. This direct manipulation of the solid state form parameter enables simultaneous improvement of both productivity (bioavailability) and reliability (dissolution profile).
3Ease of manufacture
If additional solid state forms of Vericiguat are developed, then processing and stability are improved, but the complexity of the formulation options increases
Solution Approach 1:
The patent applies segmentation by categorizing Vericiguat into distinct polymorphic forms with well-defined characteristics. Rather than presenting a complex continuum of options, the invention segments the solid state space into discrete, manageable polymorphs, each with specific processing and stability properties. This segmentation simplifies formulation development by providing clear options rather than overwhelming complexity.
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 new solid state forms of Vericiguat provide improved processing, stability, and bioavailability, facilitating better pharmaceutical formulations and treatments for chronic heart failure.
Implementation Method 1
The present disclosure provides crystalline polymorphs or salts of Vericiguat, particularly Vericiguat hydrochloride, processes for preparation thereof
Data Source
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AI summary
The present disclosure encompasses solid state forms of Vericiguat, in embodiments crystalline polymorphs of Vericiguat, processes for preparation thereof, and pharmaceutical compositions thereof.