Encequidar Mesylate Crystalline Forms Stability Bioavailability
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Solution Overview
Problem
Current solid state forms of Encequidar and Encequidar mesylate have limitations in terms of polymorphism, stability, and bioavailability, which affect their efficacy and handling characteristics, particularly when used in combination with Paclitaxel for treating metastatic breast and gastric cancer.
Innovation Solution
Development of new solid state forms, including crystalline forms like Form IV, Form K, and Form L, characterized by specific PXRD patterns and NMR spectra, which enhance chemical stability, bioavailability, and processing properties, and their use in pharmaceutical compositions with Paclitaxel.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing solid state forms of Encequidar and Encequidar mesylate are used, then the compound can be formulated for pharmaceutical use, but the stability and bioavailability are limited
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing multiple polymorphic forms (Forms I, II, III, IV) of Encequidar and Encequidar mesylate, each with distinct crystal structures and physical properties. These different polymorphic forms exhibit variations in stability, solubility, and bioavailability, allowing selection of the optimal form for pharmaceutical formulation. The invention systematically investigates and compares the properties of each polymorph to identify those with improved therapeutic performance.
2Ease of manufacture
If existing solid state forms are used, then formulation is possible, but handling characteristics are suboptimal
Solution Approach 1:
The patent applies local quality by characterizing specific regions or aspects of each polymorphic form's properties. Different polymorphic forms exhibit local variations in crystal habit, particle morphology, flowability, compressibility, and dissolution rate. By identifying and utilizing these localized property differences, the invention enables optimization of manufacturing processes and handling characteristics for each specific polymorphic form while maintaining or improving therapeutic efficacy.
3Productivity
If new solid state forms are developed, then stability and bioavailability are improved, but the complexity of characterization and selection increases
Solution Approach 1:
The patent applies preliminary action by conducting comprehensive upfront characterization of multiple polymorphic forms using various analytical techniques (PXRD, DSC, TGA, solid-state NMR, IR spectroscopy). This preliminary investigation establishes a detailed understanding of each form's properties, stability profile, and performance characteristics before pharmaceutical development proceeds. By performing this characterization work in advance, the invention reduces subsequent complexity in formulation development and regulatory approval processes.
Data Source
AI summary
The present disclosure relates to solid state forms of Encequidar and Encequidar mesylate, processes for their preparation, and pharmaceutical compositions thereof.