Selexipag Solid State Forms IV and V
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Solution Overview
Problem
There is a need for additional solid state forms of Selexipag, including solvated forms, to improve processing properties, stability, and bioavailability for the treatment of arteriosclerosis obliterans, pulmonary hypertension, and Raynaud's disease secondary to systemic sclerosis.
Innovation Solution
The development of new solid state forms of Selexipag, such as Form IV and Form V, characterized by specific XRPD patterns, DSC, TGA, Raman, and NMR spectra, which offer enhanced solubility, stability, and handling characteristics, and their use in pharmaceutical compositions for improved treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing solid state forms of Selexipag are used, then the basic therapeutic function is achieved, but processing properties and stability are insufficient
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing different polymorphic forms (Forms I, II, III, IV, V) of Selexipag, each with distinct crystal structures and physical properties. By changing the solid state form parameter, the invention achieves improved processing properties, stability, solubility, and dissolution profile while maintaining the therapeutic function
Solution Approach 2:
The patent creates composite materials by forming solvates of Selexipag with various solvents (ethanol solvate, isopropyl alcohol solvate, acetone solvate, etc.). These composite solid state forms combine the active pharmaceutical ingredient with solvent molecules in a defined stoichiometric ratio, providing enhanced stability and processing characteristics
2Reliability
If existing solid state forms of Selexipag are used, then the therapeutic function is achieved, but solubility and bioavailability are limited
Solution Approach 1:
The patent systematically explores different solid state forms (polymorphs and solvates) to change the physical parameter of solubility. Each polymorphic form and solvate presents a different crystal packing arrangement that affects dissolution rate and bioavailability, providing formulation scientists with options to optimize therapeutic outcome
Solution Approach 2:
The patent uses solvents as intermediary substances to form solvates with Selexipag. These solvent molecules act as mediators that modify the solid state properties of the API, particularly solubility and dissolution profile, without affecting the chemical structure or therapeutic activity of Selexipag
Data Source
AI summary
The present disclosure relates to solid state forms of Selexipag, in particular selexipag forms IV and V, and processes for preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.