Pharmaceutical Composition Stability via Segmented Granulate Blending
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Solution Overview
Problem
The stability of pharmaceutical compositions containing both angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers is compromised due to degradation issues, particularly in the presence of water, alcohols, and mechanical stress, leading to ineffective therapeutic outcomes and non-compliance with chemical purity standards.
Innovation Solution
A stable pharmaceutical composition is achieved by blending a powder containing an ACE inhibitor (such as ramipril or perindopril) with a granulate of a calcium channel blocker (like amlodipine) without physical separation, using pharmaceutically acceptable excipients, and minimizing mechanical treatment to maintain degradant levels within acceptable limits without the need for stabilizing agents or pH adjustment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If physical separation of ACE inhibitor and calcium channel blocker is implemented, then stability of the composition is improved, but device complexity and manufacturing complexity increase
Solution Approach 1:
The invention segments the formulation into two distinct granulate types: one containing the ACE inhibitor with stabilizing excipients, and another containing the calcium channel blocker. These segmented granulates are then combined in a simple 1:1 ratio, achieving stability through segmentation while avoiding the complexity of coated tablets or capsule systems.
Solution Approach 2:
The invention introduces specific excipients as intermediaries: lactose monohydrate and/or microcrystalline cellulose as stabilizing agents for the ACE inhibitor granulate, and magnesium stearate as a lubricant. These intermediary substances mediate the interaction between the two active ingredients, preventing degradation without requiring physical separation or complex coating systems.
2Stability of the object's composition
If stabilizing agents and pH adjustment are used, then stability of the composition is improved, but manufacturing precision and process complexity increase
Solution Approach 1:
The invention changes the chemical parameters of the formulation by selecting specific excipients with known stabilizing properties (lactose monohydrate, microcrystalline cellulose) and controlling their ratios. This parameter-based approach achieves stability through compositional modification rather than complex pH adjustment or multiple stabilizing agents, simplifying the manufacturing process.
3Ease of manufacture
If mechanical treatment is applied during manufacturing, then ease of manufacture is improved, but stability of the composition deteriorates due to increased degradants
Solution Approach 1:
The invention performs preliminary granulation of each active ingredient separately with its specific excipients before combining them. This preliminary action allows each component to be optimized independently, and the subsequent simple mixing step minimizes mechanical stress on the ACE inhibitor, reducing degradant formation while maintaining ease of manufacture.
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 pharmaceutically acceptable levels of degradants, ensuring stability and effectiveness during storage and use, while simplifying the manufacturing process and reducing costs associated with physical separation and stabilizer use.
Implementation Method 1
In the case of calcium channel blockers degradation occurs primarily in the presence of water and alcohols, leading to hydrolysis, transesterification or oxidation
Implementation Method 2
In the case of calcium channel blockers degradation occurs primarily in the presence of water and alcohols, leading to hydrolysis, transesterification or oxidation
Implementation Method 3
In the case of ACE inhibitors degradation occurs most frequently in contact with water or under elevated temperature, leading to the esterification, dehydration or hydrolysis
Data Source
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AI summary
A pharmaceutical composition in the form of a blend consisting of a) a powder containing an ACE inhibitor, and b) a granulate containing a calcium channel blocker, wherein the powder a) and the granulate b) contain one or more excipients. The composition is useful in the treatment of hypertension related conditions.