Vadadustat Solid Forms Polymorph Segmentation
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Solution Overview
Problem
There is a need for solid forms of Vadadustat ({[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid) with desirable pharmaceutical properties for use in treating and preventing anemia associated with chronic kidney disease, as existing forms have varying physical and chemical properties that affect processing, stability, and bioavailability.
Innovation Solution
The development of specific solid forms, such as Form D, E, F, HB, SA, SB, SC, SD, SE, and SF, characterized by distinct X-ray powder diffraction patterns and thermal analysis profiles, which are prepared through methods involving slow cooling, super-saturation, and crystallization from various solvents, ensuring high purity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If different solid forms of Compound 1 are prepared, then pharmaceutical properties such as stability and bioavailability can be optimized, but the complexity of identifying and selecting the desired solid form increases
Solution Approach 1:
The patent segments the solid forms of Compound 1 into distinct polymorphic forms (Forms A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z) each with unique X-ray powder diffraction patterns. This segmentation allows researchers to identify and select specific solid forms based on their pharmaceutical properties without being overwhelmed by the overall complexity of all possible solid forms.
Solution Approach 2:
The patent utilizes parameter changes in the crystallization process (solvent type, temperature, pH, concentration) to generate different polymorphic forms of Compound 1. By systematically varying these parameters, the desired solid form with optimal pharmaceutical properties can be obtained and identified through characteristic X-ray powder diffraction patterns.
2Ease of manufacture
If solid forms with desirable pharmaceutical properties are developed, then processing and storage characteristics are improved, but the manufacturing process complexity increases
Solution Approach 1:
The patent performs preliminary characterization of different solid forms through X-ray powder diffraction, differential scanning calorimetry, and other analytical methods before selecting the optimal form for manufacturing. This preliminary action ensures that the desired processing and storage characteristics are achieved while avoiding unnecessary complexity in the manufacturing process by selecting the most suitable polymorphic form in advance.
3Productivity
If multiple solid forms are characterized and identified, then the ability to optimize bioavailability is improved, but the time and resources required for identification increase
Solution Approach 1:
The patent replaces complex and time-consuming trial-and-error methods with systematic characterization using X-ray powder diffraction analysis. Each polymorphic form has a unique diffraction pattern that serves as a fingerprint for rapid identification. This substitution of analytical methodology significantly reduces the time and resources required to identify and optimize solid forms for improved bioavailability.
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
These solid forms exhibit improved stability, purity, and bioavailability, making them suitable for oral pharmaceutical dosage forms and effective in treating anemia related to chronic kidney disease.
Implementation Method 1
the solid forms of Compound 1 are identifiable on the basis of groups of peaks in an X-ray powder diffraction analysis
Implementation Method 2
crystallization from various solvents
Implementation Method 3
slow cooling, super-saturation, and crystallization
Data Source
AI summary
Provided herein are solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid (Vadadustat, Code: AKB-6548, Compound 1), compositions comprising such solid forms, and methods of making and using thereof.