Glucokinase Activator Formulation for Once-Daily Dosing
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Solution Overview
Problem
Current glucokinase activator formulations, such as Dorzagliatin, require twice-daily dosing, which can lead to decreased patient compliance and potential reduction in daily doses.
Innovation Solution
Development of immediate-release, extended-release, or combination formulations of glucokinase activators like Dorzagliatin or its prodrugs, designed to provide once-a-day therapy, maintaining similar bioavailability and extending the mean residence time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glucokinase activator is administered twice daily, then blood glucose control is maintained, but patient compliance decreases and dosing complexity increases
Solution Approach 1:
The patent divides the dosing regimen into two distinct formulation components: an immediate-release formulation providing rapid glucose-lowering effect, and an extended-release formulation providing sustained effect. This segmentation allows the drug to achieve both rapid onset and prolonged duration, enabling once-daily administration while maintaining glucose control reliability.
Solution Approach 2:
The extended-release formulation component ensures continuous release of the glucokinase activator over 24 hours, maintaining therapeutic blood levels throughout the dosing interval. This continuous action eliminates the need for twice-daily dosing while preserving glucose control, directly improving patient compliance.
2Speed
If immediate-release formulation is used, then rapid glucose-lowering effect is achieved, but duration of action is insufficient for once-daily dosing
Solution Approach 1:
The patent combines two formulation types with complementary characteristics into a single composite formulation. The immediate-release component provides rapid onset by quickly releasing the drug into circulation, while the extended-release component simultaneously provides prolonged duration through controlled release mechanisms. This merging allows both rapid action and sustained effect to coexist in one dosing event.
Solution Approach 2:
The formulation exhibits dynamic release characteristics, transitioning from rapid initial release to sustained prolonged release. The immediate-release portion delivers the drug quickly for fast onset, then the extended-release portion takes over to maintain therapeutic levels, creating a dynamic release profile that adapts to different phases of therapeutic need within the same dosing interval.
3Duration of action of moving object
If extended-release formulation is used, then duration of action is extended, but onset of action becomes slower
Solution Approach 1:
The patent merges immediate-release and extended-release formulations in a composite structure where both release mechanisms operate simultaneously. The immediate-release component ensures rapid onset by quickly delivering therapeutic levels of the drug, while the extended-release component ensures prolonged duration. This combination eliminates the trade-off between onset speed and duration that exists in single-formulation approaches.
Data Source
AI summary
Provided herein are pharmaceutical formulations comprising glucokinase activator, or a prodrug, or a pharmaceutically acceptable salt, an isotope labeled analogue, a crystalline form, a hydrate, a solvate, or a diastereomeric or enantiomeric form thereof and the use thereof for treating diseases; the pharmaceutical formulations are in the form of immediate-release formulations, extended-release formulations, or combination of immediate-release formulation and extended-release formulations. The pharmaceutical formulations achieved once-a-day therapy for some diseases, in particular, type II Diabetes Mellitus with obesity. The pharmaceutical formulations exhibit sustained 24 hours of glucose-lowering effects. The pharmaceutical formulations also achieved lower Cmax, extended T1/2 as well as maintained similar bioavailability and increased MRT compared with commercial Dorzagliatin tablet, enhanced the pharmacology effect of restoring the glucose stimulated GLP-1 secretion in diabetes with obesity.