Magnesium Isoglycyrrhizinate Crystalline Forms
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Solution Overview
Problem
The variability in crystalline forms of pharmaceutical compounds like magnesium isoglycyrrhizinate affects their melting points, solubility, stability, and biological activity, making it challenging to ensure uniformity and consistency in drug preparation and storage stability.
Innovation Solution
The identification and characterization of specific crystalline forms (A, B, C, D, E) of magnesium isoglycyrrhizinate, including their X-ray powder diffraction patterns, water content, specific surface area, and particle size distribution, to establish stable and consistent formulations for pharmaceutical use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If different crystalline forms of magnesium isoglycyrrhizinate are used, then solubility and bioavailability may be improved, but manufacturing precision and consistency deteriorate due to variability in physical properties
Solution Approach 1:
The patent applies parameter changes by systematically varying crystallization conditions including solvent composition (water-ethanol ratios), temperature profiles (cooling rates from 0.5 to 5°C per hour), and pH values (adjusted to specific ranges) to obtain different crystalline forms with distinct physical properties. This enables control over solubility and bioavailability while maintaining manufacturing consistency through defined parameters.
Solution Approach 2:
The patent utilizes phase transitions during the crystallization process, where magnesium isoglycyrrhizinate transitions from dissolved state to various crystalline forms (Forms I-VI) with different molecular arrangements. By controlling the phase transition conditions, the patent achieves consistent production of specific crystalline forms with desired solubility and bioavailability characteristics.
2Reliability
If crystalline forms are optimized for higher solubility, then bioavailability improves, but stability deteriorates due to increased sensitivity to environmental conditions
Solution Approach 1:
The patent employs parameter changes to identify optimal crystallization conditions for each crystalline form, including specific solvent ratios, temperatures, and pH levels. This enables the production of crystalline forms with balanced solubility and stability profiles, where higher solubility forms are obtained under controlled conditions that also define their stability characteristics.
Solution Approach 2:
The patent applies inversion by characterizing and defining the properties of less soluble but more stable crystalline forms, then using these as reference standards to control and reproduce the desired crystalline form in manufacturing. This reverse approach ensures that stability-critical forms are used as benchmarks for quality control.
3Reliability
If multiple crystalline forms are characterized to extend physical properties, then bioavailability can be optimized, but device complexity increases due to need for precise crystallization control
Solution Approach 1:
The patent applies segmentation by dividing the crystallization process into distinct stages with specific parameter ranges for each crystalline form (Forms I-VI). Each form has defined preparation conditions including solvent composition, temperature ranges, and pH levels, allowing systematic control and reproduction of specific crystalline forms without requiring complex integrated control systems.
Solution Approach 2:
The patent uses parameter changes to define specific crystallization conditions for each crystalline form, including solvent ratios (water-ethanol), temperatures (cooling rates), and pH values. These defined parameters simplify process control by providing clear target values and ranges for each crystalline form, reducing the need for complex real-time adjustments.
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 characterization of these crystalline forms enhances the physical properties and stability of magnesium isoglycyrrhizinate, improving drug preparation, storage stability, and bioavailability, and providing a basis for uniform pharmaceutical compositions.
Implementation Method 1
using Cu-Kα radiation, the crystalline form A has an X-ray powder diffraction (XRD) pattern comprising diffraction peaks at 2θ value (°) of about 3.57, 7.10, 13.83, 14.65 and 15.48
Data Source
AI summary
This application belongs to the field of pharmaceutical technology, and relates to the crystals of glycyrrhizic acid derivatives, their crystalline and pharmaceutical compositions, and medical use thereof, and, in particular, to the crystalline form A, crystalline form B, crystalline form C, crystalline form D, and crystalline form E of magnesium isoglycyrrhizinate, the method of preparing the crystals, the crystalline and pharmaceutical compositions containing the crystals, and medical use thereof. The crystalline forms prepared according to this application have overcome the defects of the compound of Formula I prepared according to the prior art, such as solid caking, difficult filtration, hard drying, and poor clarity. They are also suitable for industrial production, and capable of improving product safety.