GLP-1R Agonist Polymorphs for Stable Oral Formulation
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Solution Overview
Problem
Current GLP-1R agonists, such as liraglutide and exenatide, are polypeptides requiring frequent injections, leading to poor patient compliance and side effects, while amorphous forms of small-molecule GLP-1R agonists are prone to water absorption and crystal form transformation, making them unsuitable for clinical formulations.
Innovation Solution
Development of stable polymorphic forms of small-molecule GLP-1R agonists, including crystal forms A to T, hydrates, and solvates, characterized by specific X-ray powder diffraction patterns and thermal analysis profiles, to enhance stability and ease of administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If polypeptide GLP-1R agonists (liraglutide, exenatide) are used, then GLP-1R agonistic activity is achieved, but frequent injections are required leading to poor patient compliance
Solution Approach 1:
The patent changes the molecular size parameter from large polypeptides to small molecules, transforming the administration route from frequent injections to oral intake, thereby improving patient compliance while maintaining GLP-1R agonistic activity
Solution Approach 2:
The patent replaces the mechanical injection system with an oral administration system, eliminating the need for frequent injections and improving ease of operation for patients
2Ease of operation
If amorphous forms of small-molecule GLP-1R agonists are used, then oral administration is enabled, but water absorption and crystal form transformation occur making them unsuitable for clinical formulations
Solution Approach 1:
The patent utilizes phase transition from amorphous to crystalline state, developing stable polymorphic forms with defined crystal structures that prevent water absorption and crystal form transformation while maintaining oral administrability
Solution Approach 2:
The patent changes the physical state parameter from amorphous to crystalline, improving physicochemical stability by establishing specific crystal forms with controlled polymorphism that prevent degradation
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 polymorphic forms provide improved physicochemical stability, facilitating industrial production and rapid absorption, addressing the issues of patient compliance and formulation suitability.
Implementation Method 1
characterized by specific X-ray powder diffraction patterns and thermal analysis profiles
Implementation Method 2
characterized by specific X-ray powder diffraction patterns and thermal analysis profiles
Data Source
AI summary
A polymorphic form of a GLP-1R agonist compound (III), a preparation method therefor and a use thereof are provided. Compared with an amorphous form of compound (III), the polymorphic form has higher stability and better processability, and is more suitable for preparing a drug for preventing or treating diseases related to a GLP-1R target and a signaling pathway thereof, such as type 2 diabetes, prediabetes, obesity, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, kidney disease, gout, hyperhematuria, cardiovascular disease, etc.