Ponatinib Hydrochloride Solvate Crystalline Forms
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Solution Overview
Problem
There is a need for new polymorphic forms of ponatinib hydrochloride and processes for their preparation, as existing forms may not offer optimal characteristics such as targeted release profiles or desired stability and solubility.
Innovation Solution
The development of crystalline forms of ponatinib hydrochloride, specifically ponatinib hydrochloride propylene glycol solvate (Form alpha) and benzyl alcohol solvate (Form beta), characterized by unique XRPD patterns, along with processes involving the formation of solutions with ponatinib hydrochloride and solvents like propylene glycol or benzyl alcohol at controlled temperatures, followed by isolation and drying methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing polymorphic forms of ponatinib hydrochloride are used, then the drug can be formulated and administered, but optimal characteristics such as targeted release profiles, stability, and solubility are not achieved
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing multiple polymorphic forms (Form A through Form H) of ponatinib hydrochloride, each with distinct crystal structures and physical properties. By changing the polymorphic form parameter, the invention achieves different stability, solubility, and release characteristics while maintaining the same chemical compound, thus resolving the contradiction between stability and targeted release profiles
Solution Approach 2:
The patent utilizes phase transitions between different crystalline polymorphic forms of ponatinib hydrochloride. Each polymorph represents a different solid phase with unique properties, allowing selection of the appropriate phase for specific pharmaceutical performance requirements such as stability versus targeted release, thereby resolving the technical contradiction
2Reliability
If existing polymorphic forms are used, then the drug can be administered, but desired solubility characteristics are not achieved
Solution Approach 1:
The patent changes the polymorphic form parameter to achieve different solubility characteristics. Different polymorphs of ponatinib hydrochloride exhibit varying solubility profiles due to their distinct crystal packing arrangements, allowing optimization of both stability and solubility by selecting the appropriate polymorphic form
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 new crystalline forms of ponatinib hydrochloride exhibit improved properties including chemical purity, stability, solubility, and reduced hygroscopicity, providing enhanced pharmaceutical characteristics.
Implementation Method 1
crystalline ponatinib hydrochloride, namely ponatinib hydrochloride propylene glycol solvate, designated as Form alpha
Implementation Method 2
maintaining the solution of step a) at a temperature of about 0° C. to about 150° C.; and isolating ponatinib hydrochloride propylene glycol solvate designated Form alpha from the solution
Data Source
AI summary
Novel crystalline ponatinib hydrochloride forms designated Form alpha and Form beta are disclosed. Form alpha is characterized by data selected from an XRPD pattern with peaks at about 6.5, 9.0, 12.25, 14.4, 16.70, 19.6, 22.2, 24.5, 28.2.+-.0.2 degrees 2-theta; an XRPD pattern substantially as depicted in FIG. 1; and/or a combination thereof. Form beta is characterized by data selected from an XRPD pattern with peaks at about 10.7, 15.2, 15.8, 16.4 23.1, 25.0, 27.8.+-.0.2 degrees 2-theta; an XRPD pattern substantially as depicted in FIG. 3; and/or combinations thereof. Processes for making Form alpha and Form beta are disclosed.