SEP-363856 Crystalline Salt Forms for Stability and Dissolution
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Solution Overview
Problem
There is a need for additional solid state forms of SEP-363856, including salts and solvates, to improve processing properties, stability, and bioavailability for the treatment of schizophrenia and Parkinson's disease psychosis.
Innovation Solution
The development of crystalline forms of SEP-363856 HBr, SEP-363856 Fumarate, SEP-363856 R-camsylate, and SEP-363856 S-camsylate, characterized by specific X-ray diffraction patterns and thermal behaviors, which can be used to prepare pharmaceutical compositions and formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a single solid state form of SEP-363856 is used, then the formulation is simple, but the processing properties, stability, and bioavailability are limited
Solution Approach 1:
The patent applies parameter changes by developing multiple solid state forms (polymorphs, salts, solvates) of SEP-363856 with different physical and chemical parameters. Each solid state form exhibits distinct properties such as solubility, stability, and bioavailability, allowing formulation scientists to select the most appropriate form for specific pharmaceutical applications while maintaining the core molecular structure of the active ingredient
Solution Approach 2:
The patent employs composite materials by creating salt forms of SEP-363856 combined with different counterions (e.g., HBr, fumarate, camsylate). These composite salt forms provide enhanced processing properties, improved stability, and optimized bioavailability compared to the free base form, expanding the formulation options without requiring development of entirely new molecular entities
2Reliability
If conventional solid state forms are used, then the manufacturing process is straightforward, but the chemical stability and shelf-life are insufficient
Solution Approach 1:
The patent applies preliminary action by pre-establishing multiple stable solid state forms and salt forms of SEP-363856 during the drug development phase. These pre-characterized forms with known stability profiles and manufacturing protocols are ready for scale-up, eliminating the need for stability optimization during commercial manufacturing and ensuring consistent chemical stability and shelf-life from the outset
Solution Approach 2:
The patent utilizes parameter changes by selecting specific solid state forms and salt forms with optimized chemical stability parameters. By changing the physical state (crystalline vs. amorphous), polymorphic form, or salt type, the chemical stability and shelf-life are significantly improved while maintaining compatibility with standard manufacturing processes through established crystallization and isolation techniques
3Ease of operation
If the current solid state forms are used, then the handling is simple, but the dissolution profile and bioavailability are suboptimal
Solution Approach 1:
The patent applies parameter changes by developing solid state forms with optimized dissolution parameters. Different polymorphs, salts, and solvates exhibit distinct dissolution rates and bioavailability profiles, allowing selection of the form that best balances handling characteristics with dissolution performance. The crystalline forms provide ease of handling while the specific crystal structure and salt form control the dissolution profile for optimal bioavailability
Data Source
AI summary
Solid state forms of SEP-363856 HBr, SEP-363856 Fumarate, SEP-363856 R-camsylate and SEP-363856 S-camsylate and processes for preparation thereof, and pharmaceutical compositions thereof.