Injection Pen Insulin Formulation Balancing Rapid Action and Stability
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Solution Overview
Problem
Existing insulin formulations, particularly rapid and ultra-rapid acting ones, face challenges with stability issues due to the removal of zinc cations, leading to impaired physical and chemical stability, aggregation, and reduced insulin action onset.
Innovation Solution
An injection pen system comprising an aqueous liquid pharmaceutical composition with insulin, ionic zinc, and an alkyl glycoside as a non-ionic surfactant, which stabilizes the insulin and enhances its rapid action.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If zinc cations are removed from insulin formulations to achieve rapid or ultra-rapid acting insulin, then the onset of insulin action is improved, but physical and chemical stability deteriorates
Solution Approach 1:
The patent introduces an intermediary substance (a specific excipient or formulation additive) that mediates between the conflicting requirements of rapid action and stability. This intermediary component allows the insulin to maintain rapid onset characteristics while preventing aggregation and degradation that would otherwise occur in zinc-free formulations.
Solution Approach 2:
The patent employs parameter changes by modifying the chemical environment of the insulin formulation through pH adjustment, ionic strength modification, or concentration optimization. These parameter changes enable the insulin to achieve rapid dissociation and action while maintaining structural integrity and preventing aggregation in the absence of zinc cations.
2Speed
If zinc cations are removed from insulin formulations to achieve rapid action, then speed of action is improved, but aggregation increases
Solution Approach 1:
The patent introduces an intermediary substance that acts as a stabilizing agent, preventing insulin molecules from aggregating while maintaining rapid action characteristics. This intermediary component interferes with the aggregation pathway, allowing fast dissociation and action without the formation of harmful aggregates.
Solution Approach 2:
The patent converts the potentially harmful effect of zinc removal (which causes aggregation) into a benefit by using the absence of zinc to achieve rapid action, while counteracting the aggregation issue through formulation optimization and protective additives.
3Productivity
If high concentrations of insulin are used to increase dosage, then productivity is improved, but stability deteriorates
Solution Approach 1:
The patent employs parameter changes by optimizing pH, ionic strength, and formulation composition to enable high insulin concentrations while maintaining stability. These parameter adjustments prevent aggregation and degradation even at elevated concentrations, allowing high productivity without sacrificing stability.
Solution Approach 2:
The patent introduces an intermediary stabilizing agent that enables high insulin concentrations to be maintained without aggregation or degradation. This intermediary component protects the insulin molecules at high concentrations, allowing increased productivity while preserving formulation stability throughout the shelf life.
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 system provides stable, rapid or ultra-rapid acting insulin compositions that maintain high insulin concentrations, reducing aggregation and ensuring swift insulin action, even at high doses, while remaining stable during storage and use.
Implementation Method 1
an alkyl glycoside as a non-ionic surfactant, which stabilizes the insulin and enhances its rapid action
Implementation Method 2
the hexameric form is absorbed from the injection site considerably more slowly than the monomeric and dimeric forms. Therefore, a faster onset of insulin action can be achieved if the hexameric form is destabilised allowing a more rapid dissociation of the zinc-bound hexamer into dimers and monomers
Data Source
AI summary
There is provided inter alia an injection pen system comprising an injector mechanism and a reservoir comprising an aqueous liquid pharmaceutical composition for delivery by means of said injector mechanism to a mammal wherein the composition comprises (i) an insulin compound, (ii) ionic zinc and (iii) an alkyl glycoside as a non-ionic surfactant.