Insulin Aspart Formulation Stability via Sodium Chloride Extraction
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Solution Overview
Problem
Current insulin formulations face challenges in maintaining chemical and physical stability, particularly due to pH sensitivity, which affects their solubility and degradation, necessitating buffering agents to maintain a pH range of 7.2 to 7.4 to prevent acidic or alkaline degradation.
Innovation Solution
A pharmaceutical formulation of insulin aspart with reduced sodium chloride content (less than 0.17 mg/mL) is developed, incorporating Zn(II), protamine, metacresol, phenol, disodium phosphate, glycerol, and pH adjustment agents to achieve a pH range of 6.0 to 9.0, enhancing chemical and physical stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If buffering agents are used to maintain pH range of 7.2 to 7.4, then chemical stability is improved, but formulation complexity increases
Solution Approach 1:
The patent removes sodium chloride from the formulation or reduces its content to less than 0.17 mg/mL, extracting the harmful component that causes instability. This eliminates the need for complex buffering systems to compensate for chloride-induced degradation, thereby maintaining chemical stability while reducing formulation complexity
Solution Approach 2:
The patent changes the pH range parameter from the conventional 7.2-7.4 to a broader range of 6.0-9.0, and specifically allows pH 7.4 without requiring strict maintenance through complex buffering. This parameter change enables simplified formulations while maintaining stability
2Stability of the object's composition
If pH is maintained in range of 7.2 to 7.4, then degradation is prevented, but solubility control becomes more difficult
Solution Approach 1:
The patent expands the acceptable pH range from 7.2-7.4 to 6.0-9.0, providing a broader window for solubility control. This parameter change allows flexibility in maintaining both degradation prevention and adequate solubility without requiring precise pH control mechanisms
3Stability of the object's composition
If sodium chloride content is reduced to less than 0.17 mg/mL, then chemical stability is improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent removes or extracts sodium chloride from the formulation to achieve less than 0.17 mg/mL content. By eliminating this component entirely or reducing it to trace levels, the formulation achieves improved chemical stability while the manufacturing challenge is addressed through removal rather than precise control
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 formulation exhibits excellent chemical and physical stability, extending shelf life and ensuring effective glucose regulation, suitable for use in diabetes treatment.
Implementation Method 1
a pharmaceutical formulation comprising (a). insulin aspart; and (b). Zn(II)
Implementation Method 2
(d). optionally protamine
Implementation Method 3
metacresol, phenol
Data Source
AI summary
Stabilized pharmaceutical formulations of insulin aspart are disclosed.