Amlodipine Besylate Oral Liquid Composition Stability
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Solution Overview
Problem
Current oral liquid formulations of amlodipine besylate face challenges such as poor stability, inaccurate dosing, and lack of standardization, particularly in pediatric and geriatric populations, who may struggle with swallowing solid dosage forms, leading to compliance issues and off-label prescribing.
Innovation Solution
An oral liquid pharmaceutical composition comprising amlodipine besylate, cyclodextrin, paraben, and water, with optional additives like curcumin, sweeteners, and flavoring agents, formulated to maintain stability and patient compliance, with cyclodextrin and curcumin enhancing solubility and stability of amlodipine besylate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If amlodipine besylate is formulated as solid oral dosage forms (tablets, pills, capsules), then manufacturing and storage are simplified, but patient compliance deteriorates in pediatric and geriatric populations who have difficulty swallowing solid dosage forms
Solution Approach 1:
The patent transforms amlodipine besylate from solid dosage form to liquid oral composition, changing the physical state parameter to improve swallowability for pediatric and geriatric patients while maintaining manufacturing feasibility through standardized liquid formulation processes
Solution Approach 2:
Cyclodextrin serves as an intermediary substance that enhances the solubility and stability of amlodipine besylate in liquid formulation, enabling the transition from solid to liquid dosage form while maintaining drug efficacy and preventing precipitation
2Ease of operation
If liquid dosage forms are prepared by extemporaneous compounding of tablets, then patient compliance improves, but dosing accuracy and stability deteriorate
Solution Approach 1:
The patent provides pre-formulated liquid oral compositions with predetermined concentrations of amlodipine besylate, eliminating the need for extemporaneous compounding and ensuring accurate dosing while maintaining patient compliance benefits of liquid formulation
Solution Approach 2:
The invention establishes specific concentration ranges (0.1-1.9 mg/mL amlodipine besylate, 5-90 mg/mL cyclodextrin) and mole ratios (5:1 to 75:1) to standardize the liquid formulation, ensuring dosing accuracy and reproducibility across different manufacturing batches
3Ease of operation
If liquid dosage forms are prepared by extemporaneous compounding, then patient compliance improves, but stability deteriorates with short shelf life
Solution Approach 1:
Cyclodextrin acts as a stabilizing intermediary that prevents degradation and precipitation of amlodipine besylate in liquid formulation, extending shelf life while maintaining the compliance advantages of liquid dosage form
Solution Approach 2:
The patent creates a composite liquid formulation combining amlodipine besylate with cyclodextrin, paraben, and other excipients in specific ratios, where the cyclodextrin inclusion complex provides enhanced stability and prevents drug degradation over extended storage periods
4Ease of operation
If liquid dosage forms are prepared by extemporaneous compounding, then patient compliance improves, but standardization deteriorates with inconsistent preparation
Solution Approach 1:
The patent provides pre-manufactured, standardized liquid oral compositions with precisely controlled ingredients and concentrations, eliminating variability in extemporaneous compounding while maintaining the compliance benefits of liquid formulation
Solution Approach 2:
The invention establishes specific concentration ranges and mole ratios to standardize the liquid formulation, ensuring consistent quality and reproducibility across different manufacturing batches and eliminating the variability inherent in extemporaneous compounding
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 exhibits enhanced stability, maintaining at least 90% of amlodipine besylate concentration over several months under various storage conditions, improving patient compliance and treatment efficacy for hypertension, heart failure, and coronary artery disease.
Implementation Method 1
cyclodextrin comprises β-cyclodextrin... a mole ratio of cyclodextrin to amlodipine besylate in the oral liquid pharmaceutical composition is in a range of about 5:1 to about 75:1
Implementation Method 2
about 0.5 mg/mL to about 4 mg/mL paraben
Implementation Method 3
The oral liquid composition exhibits enhanced stability, maintaining at least 90% of amlodipine besylate concentration over several months under various storage conditions
Data Source
AI summary
The present disclosure provides oral liquid compositions comprising amlodipine besylate with favorable solubility and stability. Also provided herein are methods of using the oral liquid compositions.