Paltusotine Mesylate Polymorphs for Stability and Bioavailability
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Solution Overview
Problem
There is a need for additional solid state forms of Paltusotine, including crystalline polymorphs and salts, to improve processing, stability, and bioavailability for the treatment of acromegaly, malignant carcinoid syndrome, and neuroendocrine tumors.
Innovation Solution
The development of crystalline polymorphs and salts of Paltusotine, particularly Paltusotine monomesylate and Paltusotine hemimesylate, with specific preparation processes, to enhance properties such as chemical stability, dissolution profile, and handling characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If additional solid state forms and salts of Paltusotine are developed, then processing characteristics, stability, and bioavailability are improved, but device complexity and formulation complexity increase
Solution Approach 1:
The patent applies parameter changes by developing multiple solid state forms (polymorphs) and salt forms of Paltusotine, each with different physical and chemical properties. By changing the crystalline structure and chemical composition parameters, the invention achieves improved stability, dissolution profile, and processing characteristics without requiring complete redesign of the formulation system
Solution Approach 2:
The invention segments the solid state forms into distinct categories (different polymorphs, monomesylate salt, hemimesylate salt, and their respective hydrates/anhydrous forms). This segmentation allows formulation scientists to select specific forms based on required properties while maintaining a manageable organizational structure through systematic classification
2Productivity
If multiple solid state forms and salts are prepared, then bioavailability and dissolution profile are improved, but manufacturing complexity and process complexity increase
Solution Approach 1:
The patent utilizes parameter changes in preparation conditions (temperature, pH, solvent composition, crystallization parameters) to obtain different solid state forms and salt forms with optimized dissolution profiles and bioavailability, rather than requiring fundamentally different manufacturing approaches
Solution Approach 2:
The patent employs intermediary substances such as mesylate salts and specific solvents as mediators to facilitate the formation of desired solid state forms. These intermediaries enable controlled crystallization and salt formation processes that improve bioavailability while using established chemical transformation methods
3Ease of operation
If new solid state forms are discovered and developed, then handling characteristics and processing ease are improved, but loss of time in characterization and validation increases
Solution Approach 1:
The patent performs preliminary characterization of solid state forms using established analytical techniques (XRD, DSC, TGA, NMR) during the development phase to establish reference data. This preliminary action enables rapid identification and selection of suitable forms for formulation without requiring extensive re-characterization during later development stages
Solution Approach 2:
By systematically varying preparation parameters to obtain forms with inherently better handling characteristics (flowability, compressibility, dissolution), the invention reduces the need for extensive post-characterization optimization, thereby reducing overall development time
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 provide improved processing, stability, and bioavailability, facilitating effective treatment of acromegaly, malignant carcinoid syndrome, and neuroendocrine tumors.
Implementation Method 1
crystalline polymorphs of Paltusotine or salts of Paltusotine
Data Source
AI summary
The present disclosure encompasses solid state forms of Paltusotine, in embodiments crystalline polymorphs of Paltusotine or salts of Paltusotine, particularly Paltusotine monomesylate and Paltusotine hemimesylate, processes for preparation thereof, and pharmaceutical compositions thereof.