Pemafibrate Solid State Forms for Stability and Bioavailability
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Solution Overview
Problem
There is a need for additional solid state forms of Pemafibrate, including solvated forms and salts, to improve processing properties, stability, and bioavailability for the treatment of hyperlipidemia, arteriosclerosis, diabetes, inflammation, and heart diseases.
Innovation Solution
The development of specific solid state forms of Pemafibrate, such as Forms A, B, C, D, and amorphous forms, characterized by unique XRPD patterns and 13C NMR spectra, which can be used to prepare pharmaceutical compositions and formulations, and converted into other forms or salts, enhancing properties like solubility, stability, and handling characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If new solid state forms of Pemafibrate are developed, then stability and bioavailability are improved, but the complexity of the formulation process increases
Solution Approach 1:
The patent applies parameter changes by developing multiple solid state forms (crystalline forms A, B, C, D and amorphous form) with different physical and chemical parameters. Each form exhibits distinct XRPD patterns, DSC profiles, and dissolution characteristics, allowing optimization of stability and bioavailability through selective parameter modification rather than complex formulation processes
Solution Approach 2:
The patent employs preliminary action by pre-characterizing multiple solid state forms with comprehensive analytical methods (XRPD, DSC, TGA, 13C NMR, dissolution testing) before formulation development. This advance characterization enables selection of the most suitable form for specific therapeutic needs, simplifying subsequent formulation processes while ensuring optimal stability and bioavailability
2Productivity
If different solid state forms are used to improve dissolution profile, then bioavailability increases, but the difficulty of detecting and measuring the correct form increases
Solution Approach 1:
The patent applies spectral fingerprinting principles by establishing unique XRPD patterns and 13C NMR spectra for each solid state form. These spectral characteristics serve as definitive identification markers, enabling easy detection and measurement of the correct form through standard analytical techniques without requiring complex measurement protocols
Solution Approach 2:
The patent creates reference standards and fingerprint profiles for each solid state form that can be copied and used as comparison templates. These reference patterns serve as benchmarks for quality control and form identification, simplifying the detection and measurement processes through direct comparison rather than complex analytical procedures
3Ease of manufacture
If multiple solid state forms are developed for formulation optimization, then processing characteristics improve, but the device complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the Pemafibrate compound into distinct solid state forms (A, B, C, D crystalline forms and amorphous form), each with optimized processing characteristics for specific manufacturing needs. This segmentation allows selection of the most appropriate form for each processing requirement without requiring complex multi-component formulation systems
Solution Approach 2:
The patent demonstrates universality by showing that the different solid state forms can serve multiple functions across various formulation types and manufacturing processes. Each form provides a combination of improved stability, enhanced dissolution, and better processing characteristics, allowing a single form to address multiple formulation challenges without increasing system complexity
Data Source
AI summary
The present disclosure relates to solid state forms of Pemafibrate processes for preparation thereof and pharmaceutical compositions thereof.