Pracinostat Crystalline Polymorphs for Stability and Bioavailability
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Solution Overview
Problem
There is a need for additional solid state forms of Pracinostat, including crystalline polymorphs and salts, to improve handling, stability, and bioavailability for the treatment of acute myeloid leukemia, as existing forms may have limitations in processing, storage, and dissolution profiles.
Innovation Solution
The development of crystalline polymorphs and salts of Pracinostat, characterized by specific X-ray powder diffraction patterns, solid-state NMR spectra, and FTIR spectra, which can be used to create pharmaceutical compositions with enhanced properties such as stability, solubility, and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If existing solid state forms of Pracinostat are used, then the basic therapeutic function is achieved, but processing, handling, and stability characteristics are limited
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing different crystalline polymorphs of Pracinostat (Forms 1-7), each with distinct crystal structures and physical properties. These polymorphs exhibit variations in melting point, thermal behavior, X-ray diffraction patterns, and solid-state NMR spectra, providing a range of materials with optimized processing, handling, and stability characteristics for pharmaceutical formulation.
Solution Approach 2:
The patent employs composite materials by creating pharmaceutical compositions that combine Pracinostat polymorphs with pharmaceutically acceptable excipients. These composite formulations leverage the enhanced properties of specific polymorphs (such as improved flowability, compressibility, or stability) to achieve optimal therapeutic delivery and storage characteristics.
2Adaptability or versatility
If different salts and solid state forms are developed, then formulation options are expanded, but the complexity of characterizing and selecting appropriate forms increases
Solution Approach 1:
The patent applies preliminary action by pre-characterizing seven distinct Pracinostat polymorphs with comprehensive analytical data including X-ray powder diffraction patterns, solid-state NMR spectra, and differential scanning calorimetry profiles. This advance characterization establishes clear identification criteria and property profiles for each polymorph, enabling formulation scientists to select appropriate forms based on predetermined criteria without facing characterization challenges during later development stages.
Data Source
AI summary
The present disclosure encompasses crystalline polymorphs of Pracinostat and of Pracinostat salts, and pharmaceutical compositions thereof.