Encequidar Solid-State Forms for Stable Formulation Processing
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Solution Overview
Problem
Existing formulations of Encequidar (HM-30181A) lack desirable properties such as ease of handling, processing, stability, and bioavailability, which are crucial for effective cancer treatment combinations like with Paclitaxel.
Innovation Solution
Development of novel solid state forms and co-crystals of Encequidar (HM-30181A) base and mesylate, including specific crystalline forms and co-crystals with additional components, to enhance properties like solubility, stability, and compatibility with other active agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional formulations of Encequidar are used, then the basic pharmaceutical activity is maintained, but the handling, processing, and stability properties are insufficient
Solution Approach 1:
The patent applies parameter changes by creating multiple solid state forms (polymorphs) of Encequidar with different crystal structures. These forms have distinct physical properties including melting points, solubility characteristics, and stability profiles. By changing the physical state parameters through controlled crystallization processes, the invention achieves improved handling, processing, and stability properties while maintaining pharmaceutical activity.
Solution Approach 2:
The patent employs composite materials by forming co-crystals of Encequidar with complementary compounds. These co-crystal structures combine the pharmacological activity of Encequidar with the desirable physical properties of the co-crystal partners, resulting in materials with enhanced stability, solubility, and processing characteristics that neither component possesses alone.
2Productivity
If conventional solid state forms are used, then the formulation process is simple, but the bioavailability and dissolution profile are suboptimal
Solution Approach 1:
The patent utilizes parameter changes by systematically varying crystal structure parameters to optimize dissolution and bioavailability. Different polymorphic forms exhibit distinct dissolution rates and bioavailability profiles, allowing selection or design of forms that maximize therapeutic effectiveness while managing formulation complexity through controlled crystallization methodologies.
Solution Approach 2:
The patent employs intermediary substances in the form of co-crystal partners that facilitate improved bioavailability. These intermediary compounds act as structural mediators that enhance the dissolution profile and absorption characteristics of Encequidar, thereby improving bioavailability while providing a framework for manageable formulation development.
3Adaptability or versatility
If multiple solid state forms are developed, then the property optimization opportunities increase, but the characterization and selection process becomes more complex
Solution Approach 1:
The patent replaces complex manual characterization procedures with advanced analytical techniques including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). These instrumental methods systematically characterize polymorphic forms and their transitions, making the detection and measurement of multiple solid state forms manageable despite the increased number of forms to be evaluated.
Solution Approach 2:
The patent implements feedback mechanisms through systematic characterization of solid state forms and selection based on performance data. By evaluating multiple forms against defined criteria (stability, solubility, processing properties) and using this feedback to guide form selection and formulation development, the complexity of characterizing multiple forms is managed through an iterative, data-driven approach.
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 solid state forms and co-crystals improve the handling, processing, and stability of Encequidar, facilitating better formulation and increased bioavailability when combined with Paclitaxel for cancer treatment.
Implementation Method 1
Solid state forms of Encequidar (HM-30181A) base, Encequidar (HM-30181A) mesylate, co-crystals of Encequidar (HM-30181A) mesylate
Data Source
AI summary
The present disclosure relates to solid state forms of Encequidar (previously referred to as HM-30181A) base, Encequidar ((HM-30181A) mesylate, co-crystals of Encequidar (HM-30181A) mesylate, processes for preparation thereof, as well as pharmaceutical compositions including the same.