Ozanimod Hydrochloride Crystalline Form CS2 Preparation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods lack a comprehensive understanding of the crystalline forms and preparation processes for ozanimod hydrochloride, limiting its pharmacological development and stability, particularly for treating multiple sclerosis and autoimmune diseases.
Innovation Solution
The discovery and characterization of a novel crystalline form, CS2, of ozanimod hydrochloride, which exhibits improved stability, solubility, and bioavailability, achieved through a process involving dissolution in a solvent mixture of tetrahydrofuran and water, followed by slow evaporation, and its use in pharmaceutical compositions for treating multiple sclerosis and ulcerative colitis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional preparation methods are used for ozanimod hydrochloride, then the drug can be produced, but the stability and solubility are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the crystallization conditions including solvent composition (tetrahydrofuran-water mixture), temperature (4°C refrigeration), and evaporation rate to obtain a specific crystalline form (CS2) with improved physicochemical stability and solubility characteristics
Solution Approach 2:
The patent utilizes phase transitions through the crystallization process where ozanimod hydrochloride transitions from dissolved state in the solvent mixture to a stable crystalline form (CS2) through controlled evaporation and refrigeration, achieving enhanced stability and uniform particle size
2Quantity of substance
If the drug has high solubility, then bioavailability improves, but hygroscopicity increases
Solution Approach 1:
The patent changes the physical and chemical parameters of the drug by obtaining a specific crystalline form (CS2) with modified molecular arrangement and crystal structure, which simultaneously achieves high solubility through improved lattice energy characteristics and reduced hygroscopicity through stable crystal packing that minimizes water interaction
3Adaptability or versatility
If comprehensive polymorph screening is performed, then better drug products can be developed, but the complexity and time required increase
Solution Approach 1:
The patent applies preliminary action by conducting comprehensive polymorph screening and identifying the optimal crystalline form (CS2) in advance through systematic investigation of different preparation methods, solvents, and conditions, thereby establishing a reliable preparation process that avoids time-consuming optimization later in development
Solution Approach 2:
The patent systematically varies preparation parameters including solvent types, temperatures, and evaporation rates to identify the optimal crystallization conditions that produce the desired CS2 form, thereby resolving the contradiction between comprehensive screening and development time by establishing an efficient parameter optimization pathway
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
Form CS2 demonstrates enhanced physicochemical stability, higher solubility, reduced hygroscopicity, and uniform particle size, ensuring consistent drug quality, improved bioavailability, and reduced toxicity, thereby enhancing the efficacy and safety of ozanimod-based treatments.
Implementation Method 1
dissolving Compound (I) hydrochloride into a solvent mixture of ethers and water
Implementation Method 2
then evaporating slowly to obtain Form CS2
Implementation Method 3
discovered crystalline form CS2 of Compound (I) hydrochloride
Data Source
AI summary
The present disclosure is related to crystalline forms of ozanimod hydrochloride, as well as preparation method thereof. The crystalline form of ozanimod hydrochloride provided by the present disclosure can be used for treating autoimmune diseases, particularly multiple sclerosis and ulcerative colitis. The crystalline form of the present disclosure has advantages in at least one aspect of solubility, melting point, stability, dissolution, bioavailability and processability and provides a new and better choice for the preparation of drug product containing ozanimod, and has significant value for drug development.