Selinexor Co-Crystal Forms for Solubility and Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing forms of selinexor do not include co-crystals with succinic acid or vanillin, which could enhance its pharmaceutical properties such as solubility and stability, and there is a need for new forms to improve its therapeutic efficacy.
Innovation Solution
The development of selinexor co-crystals with succinic acid Forms I and II, and vanillin Form I, through specific preparation methods involving solvents and anti-solvents, leading to anhydrous crystalline forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing forms of selinexor are used, then the current pharmaceutical properties are maintained, but solubility and stability are insufficient for improved therapeutic efficacy
Solution Approach 1:
The patent applies composite materials by forming co-crystals of selinexor with coformers (succinic acid or vanillin). This creates a composite solid form where selinexor molecules are arranged in a crystalline structure with coformer molecules, achieving improved solubility and stability while maintaining the therapeutic activity of selinexor. The co-crystal form combines the properties of both components to enhance pharmaceutical performance.
2Stability of the object's composition
If new co-crystal forms are developed, then solubility and stability are improved, but the complexity of the preparation process increases
Solution Approach 1:
The patent employs parameter changes by systematically varying crystallization conditions including solvent types (ethyl formate, methanol, 1-propanol, ethyl acetate, isopropanol, acetone), temperature ranges (0°C to 60°C), and anti-solvent addition to obtain different co-crystal forms (Form I and Form II with succinic acid, Form I with vanillin). This approach enables optimization of solubility and stability while managing preparation complexity through controlled parameter adjustment.
Solution Approach 2:
The patent uses solvents and anti-solvents as intermediaries to facilitate the formation of co-crystals. These intermediary substances mediate the interaction between selinexor and coformers during crystallization, enabling the formation of stable co-crystal structures without requiring direct complex interactions between the active ingredient and coformer under all conditions.
3Reliability
If co-crystals with succinic acid or vanillin are formed, then pharmaceutical properties are enhanced, but the manufacturing process requires additional steps
Solution Approach 1:
The patent applies preliminary action by pre-dissolving selinexor and coformers in suitable solvents before crystallization. This preliminary dissolution step ensures complete mixing and proper molecular distribution, facilitating subsequent co-crystal formation during the crystallization process. The pre-prepared solutions are then subjected to controlled crystallization conditions to yield the desired co-crystal forms.
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 co-crystals exhibit improved solubility and stability, enabling more effective pharmaceutical compositions for treating diseases like relapsed multiple myeloma and other cancers.
Implementation Method 1
The present invention is directed to selinexor co-crystal forms; more particularly to two co-crystal forms with succinic acid as the coformer and a co-crystal form with vanillin as the coformer
Implementation Method 2
The present disclosure is also related to processes for the preparation of the forms of selinexor co-crystals with succinic acid and the form of selinexor co-crystals with vanillin
Implementation Method 3
leading to anhydrous crystalline forms
Data Source
AI summary
The present invention is directed to selinexor co-crystal forms; more particularly to two co-crystal forms with succinic acid as the coformer and a co-crystal form with vanillin as the coformer. The present disclosure is also related to processes for the preparation of selinexor co-crystal forms. Further, the present invention also relates to pharmaceutical compositions comprising a selinexor co-crystal form and method for treating disease using a selinexor co-crystal form.