Spray-Dried Solid Glucokinase Activator Formulations for Bioavailability
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Solution Overview
Problem
Existing oral antidiabetic agents for type 2 diabetes, such as sulfonylureas and biguanides, have undesirable side-effects and fail to provide desirable glycemic control, necessitating the development of stable, bioavailable solid compositions for glucokinase activators like UD1 that can be administered frequently for effective glucose phosphorylation and insulin reduction.
Innovation Solution
Formulations of glucokinase activators, such as UD1-FA, are developed with a water-soluble surfactant and pharmaceutically acceptable excipients, using spray drying to create stable crystalline forms like Form A, ensuring release in low-pH media for absorption in the GI tract.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucokinase activators are administered orally multiple times a day, then glycemic control is improved, but patient convenience deteriorates
Solution Approach 1:
The patent applies preliminary action by formulating the glucokinase activator in a solid oral dosage form that is designed to release the active ingredient in the stomach, enabling once-daily administration. The formulation is prepared in advance with appropriate excipients and processing methods to ensure sustained release characteristics, eliminating the need for multiple daily doses while maintaining glycemic control effectiveness.
2Ease of operation
If the GK activator is formulated as a solid oral dosage form, then patient compliance is improved, but stability and release properties become more difficult to control
Solution Approach 1:
The patent applies parameter changes by systematically adjusting formulation parameters including the selection of specific excipients, pH levels, and processing conditions during solid dosage form manufacturing. These controlled parameter changes enable precise control over the release characteristics of the glucokinase activator in the gastrointestinal tract while maintaining solid oral dosage form stability and manufacturability.
Solution Approach 2:
The patent uses excipients as intermediary substances that mediate between the glucokinase activator and the gastrointestinal environment. These intermediaries control the release rate and enhance the stability of the active ingredient during formulation and administration, enabling reliable release properties in the stomach while maintaining solid dosage form integrity.
3Reliability
If the GK activator is administered frequently, then glycemic control is improved, but the complexity of the dosing regimen increases
Solution Approach 1:
The patent applies continuity of useful action by designing a solid oral dosage form that provides sustained release of the glucokinase activator over an extended period. This continuous action mechanism maintains effective glycemic control throughout the dosing interval with a single administration, eliminating the need for complex multiple-dose regimens while preserving therapeutic effectiveness.
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 formulations enhance stability, bioavailability, and pharmacokinetic profile of glucokinase activators, providing effective glycemic control and insulin sensitivity with reduced frequency of administration.
Implementation Method 1
the solid composition further comprises a water-soluble surfactant
Implementation Method 2
removing the solvent from the mixture. In some embodiments, the removing step comprises spray drying
Data Source
AI summary
The invention relates to solid compositions comprising {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid, and methods of making and using such solid compositions.