ITF 2357 Polymorph Form II Solubility
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Solution Overview
Problem
The existing monohydrate polymorph form of ITF 2357 is unstable, hygroscopic, and difficult to handle, limiting its industrial application due to low water solubility, which affects its bioavailability and dosage forms.
Innovation Solution
A novel crystalline polymorph form II of ITF 2357 with enhanced water solubility is developed, characterized by specific PXRD, DSC, TGA, and FTIR profiles, obtained through crystallization techniques using various solvents, demonstrating stability and improved handling properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If the monohydrate polymorph form I is used, then the compound is stable and easier to handle, but the water solubility is low
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing a new polymorph form (form II) with different crystal structure parameters. This polymorph exhibits enhanced water solubility (1.47 times greater than form I) while maintaining stability, resolving the contradiction between stability and solubility through structural parameter modification.
2Ease of manufacture
If the anhydrous product is used, then the compound can be prepared, but it is hygroscopic and deliquescent making it difficult to handle
Solution Approach 1:
The patent resolves the handling difficulty of the anhydrous form by transforming it into a crystalline monohydrate form through controlled hydration. This parameter change from anhydrous to monohydrate state eliminates hygroscopicity and deliquescence while maintaining ease of manufacture, making the compound much easier to handle industrially.
3Reliability
If the monohydrate polymorph form I is used, then the compound is stable and easier to handle, but the bioavailability is limited due to low water solubility
Solution Approach 1:
The patent addresses the bioavailability limitation by discovering polymorph form II, which has different crystal packing parameters that result in 1.47 times greater water solubility compared to form I. This parameter change in solubility directly improves bioavailability while the stability characteristic is maintained, resolving the contradiction between reliability and quantity of substance availability.
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 II exhibits 1.47 times greater solubility than the monohydrate form, enhancing bioavailability and stability, allowing for more versatile dosage forms and improved pharmaceutical formulations.
Implementation Method 1
A novel crystalline polymorph form II of ITF 2357 with enhanced water solubility is developed, characterized by specific PXRD, DSC, TGA, and FTIR profiles, obtained through crystallization techniques using various solvents
Data Source
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AI summary
Herein described is a novel crystalline form of the hydrochloride of the (4- hydroxycarbamoyl-pheny3)-carbamic acid (6-dimethylamino methyl-2- naphtalenyl) ester. In particular, herein described is a polymorph of the hydrochloride of the (4- hydroxycarbamoyl-phenyl)-carbamic acid (6-dimethylamino methyl-2- naphtalenyl) ester, characterized by a Powder X Ray Diffraction spectrum as indicated in Figure 1, and/or by a DSC profile as indicated in figure 2, and/or by a TGA profile as indicated in figure 3 and/or by an IR spectrum as indicated in figure 4.