AST-3424 Injection Solvent Composition for Long-Term Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The development of a stable dosage form for the cancer drug AST-3424 is hindered by its yellowish liquid nature, making oral administration difficult, and conventional injections with water as a solvent are not stable enough for long-term clinical trials and commercial production.
Innovation Solution
A concentrated AST-3424 injection preparation is formulated using a solvent mixture of C2-C8 monohydric and C2-C8 dihydric alcohols, with additives like antioxidants and protective gases, and is packaged in a neutral borosilicate glass vial to enhance stability and compatibility with human administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional water-based injection is used, then ease of manufacture is improved, but stability of the compound is worsened
Solution Approach 1:
The patent changes the solvent parameters from water-based to organic solvent-based (ethanol, propylene glycol, or their mixtures). This parameter change resolves the contradiction by providing a solvent system that simultaneously maintains manufacturability and significantly improves the stability of AST-3424 for long-term storage and clinical trials.
Solution Approach 2:
The patent employs composite solvent systems combining ethanol and propylene glycol in specific ratios (e.g., 4:1, 3:2, 1:1, or 1:2 v/v). This composite approach optimizes both ease of manufacture and stability by leveraging the complementary properties of each solvent component.
2Ease of operation
If AST-3424 is formulated as oral dosage form, then ease of operation is improved, but stability is worsened due to yellowish liquid nature
Solution Approach 1:
The patent changes the physical state parameters by formulating AST-3424 as a concentrated injection solution in organic solvents. This resolves the stability issue of the yellowish liquid form while maintaining ease of operation through standardized injection administration and simple dilution procedures before use.
3Stability of the object's composition
If concentrated injection is prepared for long-term storage, then stability is improved, but complexity of preparation increases
Solution Approach 1:
The patent performs preliminary stabilization by preparing the compound in a stable organic solvent system (ethanol/propylene glycol mixture) at the manufacturing stage. This preliminary action ensures long-term stability during storage and transportation, while the actual administration remains simple through straightforward dilution with isotonic saline or glucose solution.
Data Source
AI summary
A stable AST-3424 injection preparation, being a solution containing 0.1-200 mg/ml or 1-200 mg/ml of AST-3424 active pharmaceutical ingredient. A solvent in the solution contains a C2-C8 monohydric alcohol. The preparation method comprises the following steps: subjecting the AST-3424 active pharmaceutical ingredient and a partial prescription volume of ethanol to a first dissolution and formulation; adding a prescription volume of propylene glycol for a second dissolution and formulation; and then adding the remaining prescription volume of ethanol for mixing and dissolving to obtain a solution containing 1-200 mg/ml of AST-3424 active pharmaceutical ingredient. Provided is an AST-3424 injection for injection, wherein the solvent is water, a glucose solution, ethanol, or propylene glycol, the solutes consist of the AST-3424 active pharmaceutical ingredient, an isotonic regulator, and a pH regulator. The concentration of the AST-3424 active pharmaceutical ingredient of the injection is 0.001-1.000 mg/ml, the pH of the injection is 6.8-10.5, and the solution is an isotonic solution.