Quinoline Drug Composition With Basic Buffer for Stable Dissolution
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Solution Overview
Problem
The quinoline derivative degrades under humidifying and warming storage conditions, leading to delayed dissolution when formulated into a pharmaceutical composition due to gelation on the surface, and existing compositions do not adequately maintain dissolution after long-term storage.
Innovation Solution
A pharmaceutical composition comprising a quinoline derivative and a basic substance, such as an alkaline earth metal salt like magnesium or calcium carbonate, along with a disintegrating agent like croscarmellose sodium, enhances dissolution and stability, even after long-term storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the quinoline derivative is formulated into a pharmaceutical composition, then it can be used as a medicament with potent angiogenesis inhibitory effect and c-Kit kinase inhibitory effect, but it degrades under humidifying and warming storage conditions
Solution Approach 1:
The patent introduces a basic substance (such as magnesium carbonate, calcium carbonate, or other basic compounds with pKa ≥ 8) as an intermediary component in the pharmaceutical composition. This basic substance acts as a buffer to maintain pH ≥ 8, which prevents the degradation of the quinoline derivative under humidifying and warming storage conditions, thereby resolving the contradiction between reliability and chemical stability.
Solution Approach 2:
The patent changes the pH parameter of the pharmaceutical composition by incorporating basic substances, maintaining the pH at 8 or higher. This parameter change creates a stable environment that prevents the quinoline derivative from degrading, thus maintaining both reliability and chemical stability during storage.
2Ease of operation
If the pharmaceutical composition absorbs moisture, then dissolution of the quinoline derivative may be delayed due to gelation on the surface, but the composition needs to maintain stability during storage
Solution Approach 1:
The basic substance serves as a mediator that prevents gelation on the surface of the composition when moisture is absorbed. By maintaining pH ≥ 8, the basic substance prevents the formation of gel structures that would delay dissolution, while simultaneously maintaining physical stability during storage.
Solution Approach 2:
The patent changes the pH parameter to maintain dissolution performance. By keeping the pH at 8 or higher through the inclusion of basic substances, the composition maintains good dissolution characteristics even after absorbing moisture during storage, preventing gelation without sacrificing stability.
3Ease of operation
If existing pharmaceutical compositions are used, then they provide initial dissolution capability, but dissolution is not maintained after long term storage
Solution Approach 1:
The patent applies preliminary action by incorporating basic substances into the pharmaceutical composition from the outset, establishing a buffer system that maintains pH ≥ 8 throughout storage. This preliminary preparation ensures that the dissolution performance is maintained over time, preventing degradation and gelation that would otherwise occur during long-term storage.
Solution Approach 2:
The patent maintains the pH parameter at 8 or higher throughout the storage period through the inclusion of basic substances. This sustained parameter control ensures that dissolution performance is maintained over time, resolving the contradiction between initial dissolution capability and long-term dissolution maintenance.
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 maintains excellent dissolution and absorption of the quinoline derivative into the body, ensuring stability and efficacy over time.
Implementation Method 1
a compound, a 5% (w/w) aqueous solution or suspension of which has a pH of 8 or more
Implementation Method 2
when the pharmaceutical composition absorbs moisture, dissolution of the quinoline derivative (I) from the pharmaceutical composition that is an active ingredient may delay because of gelation on the surface of the composition
Data Source
AI summary
A pharmaceutical composition comprising a compound represented by the formula (I) or pharmaceutically acceptable salt thereof or solvate thereof; and a basic substance is excellent in dissolution, is stable even after a long term storage, and is useful as a preventive or therapeutic agent against a tumor:wherein, R1 is a hydrogen atom, a C1-6 alkyl group or a C3-8 cycloalkyl group; and R2 is a hydrogen atom or a methoxy group.