Pazopanib HCl Form F Crystallization for Acidic Solubility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current polymorphs of Pazopanib hydrochloride (Pazopanib HCl) exhibit varying solubility, particularly in acidic conditions, which affects the dissolution and performance of pharmaceutical products containing Pazopanib HCl.
Innovation Solution
A novel crystalline form F of Pazopanib HCl is developed, characterized by specific X-ray diffraction peaks and prepared through processes involving the reaction of N-(2-chloropyrimidin-4-yl)-N,2,3-trimethyl-2H-indazol-6-amine with 5-amino-2-methylbenzenesulfonamide in a solvent system, including methanol, to enhance solubility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If crystalline form A of Pazopanib HCl is used, then the pharmaceutical product can be manufactured with current processes, but the solubility in acidic condition is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the crystallization conditions (solvent system composition, temperature, pH) to obtain a new polymorph (Form F) with different solubility characteristics. Specifically, the invention uses a methanol-water-acid solvent system with controlled temperature cooling to induce crystallization of the novel polymorph that exhibits superior solubility in acidic conditions compared to Form A
Solution Approach 2:
The patent utilizes phase transitions by controlling the crystallization process from solution to solid phase. The invention involves heating the solvent system to dissolve the compound, then cooling it to induce crystallization of the desired polymorph. This phase transition control allows selective formation of Form F with improved solubility properties
2Reliability
If a novel polymorph with better solubility is developed, then the dissolution performance is improved, but the preparation process requires optimization
Solution Approach 1:
The patent optimizes preparation process parameters including solvent ratios (methanol-water-acid), temperature profiles (heating to dissolution temperature, then controlled cooling), and pH conditions to reliably produce Form F. These parameter optimizations balance the improved dissolution performance with a manageable preparation process that can be scaled for manufacturing
3Ease of manufacture
If crystalline form A is used for oral tablets, then the formulation can be produced with standard carriers, but the solubility limitation affects dissolution
Solution Approach 1:
The patent changes the crystal structure parameters by producing a novel polymorph (Form F) through controlled crystallization from a methanol-water-acid solvent system. This polymorph exhibits different packing arrangements that result in improved solubility in acidic conditions while maintaining compatibility with standard oral tablet formulation carriers and manufacturing processes
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 novel polymorph, Pazopanib HCl Form F, demonstrates improved solubility in acidic conditions, enhancing the dissolution of oral pharmaceutical formulations and providing better stability for long-term storage.
Implementation Method 1
The novel polymorph, Pazopanib HCl Form F, demonstrates improved solubility in acidic conditions... characterized by an X-ray diffraction (XRD) pattern having peaks at about 11.3, 14.6, 16.9, 19.5, 19.7, 23.5 and 25.9°±0.2° 2θ
Implementation Method 2
A novel crystalline form F of Pazopanib HCl is developed... prepared through processes involving the reaction of N-(2-chloropyrimidin-4-yl)-N,2,3-trimethyl-2H-indazol-6-amine with 5-amino-2-methylbenzenesulfonamide in a solvent system, including methanol, to enhance solubility and stability
Data Source
AI summary
The present disclosure provides a crystalline form F of Pazopanib HCl, which is characterized by an X-ray diffraction (XRD) pattern having peaks at about 11.3, 14.6, 16.9, 19.5, 19.7, 23.5 and 25.9°±0.2° 2θ. The present disclosure also provides a preparation process of a crystalline form F of Pazopanib HCl.