Insulin Glargine Biphasic Composition pH Control
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Solution Overview
Problem
Current insulin formulations, particularly insulin glargine, cannot be readily mixed with other insulins due to differences in isoelectric points, leading to uncontrolled precipitation and making it difficult to administer a reliable dose.
Innovation Solution
A stable biphasic pharmaceutical composition comprising insulin glargine in suspension form, insulin aspart, at least two amino acids (arginine and isoleucine) in a specific weight ratio, and optional pharmaceutically acceptable excipients, with a pH between 6.0 and 8.0, which allows for stable mixing and administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If insulin glargine is mixed with other insulins having different isoelectric points, then the number of injections is reduced, but uncontrolled precipitation occurs making dose administration unreliable
Solution Approach 1:
The patent modifies the pH parameter of the insulin glargine composition to fall within the range of 3.0 to 5.7, matching the isoelectric point range of other insulins. This parameter change prevents precipitation upon mixing while maintaining the stability and efficacy of insulin glargine, thereby enabling reliable co-administration with rapid-acting insulins in a single injection.
Solution Approach 2:
The patent introduces specific excipients as intermediaries to mediate between insulin glargine and other insulins. These excipients act as stabilizing agents that prevent unwanted interactions and precipitation when insulins with different isoelectric points are mixed, enabling reliable co-administration.
2Adaptability or versatility
If insulin glargine is mixed with insulins having isoelectric points between 4.0 to 5.7, then mixing compatibility is improved, but precipitation still occurs prior to injection
Solution Approach 1:
The patent precisely controls the pH parameter of insulin glargine to fall within 3.0 to 5.7, which matches the isoelectric point range of compatible insulins. This parameter adjustment ensures that when mixed, the insulins remain in a stable state without precipitating, thereby maintaining composition stability while achieving mixing compatibility.
Solution Approach 2:
The patent creates a composite pharmaceutical composition by combining insulin glargine with specific excipients and other insulins in controlled proportions. This composite formulation ensures stability and prevents precipitation by maintaining the appropriate pH balance and physical-chemical properties throughout the mixture.
3Productivity
If different types of insulin are mixed prior to administration, then the number of injections is reduced, but it becomes difficult to predict the exact dose administered
Solution Approach 1:
The patent standardizes the pH parameter of insulin glargine to fall within 3.0 to 5.7, creating predictable and consistent mixing behavior with other insulins. This parameter control ensures that the mixture remains stable and allows for accurate dose prediction, as the insulins will not precipitate or separate unpredictably upon mixing.
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 composition is stable for at least 6 months at 25°C and relative humidity of 60%, enabling reliable mixing with other insulins and reducing the number of injections required for patients.
Implementation Method 1
The two amino acids are arginine and isoleucine... wherein the pharmaceutical composition has a pH between about 6.0 to about 8.0
Implementation Method 2
mixing of different types of insulin prior to administration is not recommended as it leads to uncontrolled precipitation after mixing
Data Source
AI summary
There is provided a pharmaceutical composition comprising: (a) insulin glargine, (b) at least two amino acids, and optionally (c) one or more pharmaceutically acceptable excipients. In particular, there is provided a pharmaceutical composition comprising: (a) insulin glargine, (b) arginine and isoleucine in a weight ratio of about 1:2, and optionally (c) one or more pharmaceutically acceptable excipients.