Colchicine Oral Liquid Composition for Room-Temperature Stability
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Solution Overview
Problem
Colchicine is unstable in solution at room temperature and prone to photodegradation, especially in the presence of glycerin, and existing additives do not prevent degradation, making it challenging to formulate a stable oral liquid dosage form.
Innovation Solution
A stable oral liquid formulation of colchicine is developed using a pharmaceutically acceptable solvent system comprising water, glycols, buffering agents, sweeteners, flavoring agents, preservatives, and dyes, with specific concentrations of citric acid, sucralose, benzyl alcohol, and dyes, ensuring stability and palatability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If colchicine is formulated as an oral liquid dosage form, then ease of administration is improved, but stability of the formulation deteriorates due to photodegradation and instability at room temperature
Solution Approach 1:
The patent introduces multiple intermediary substances including antioxidants (ascorbic acid, tocopherol), chelating agents (EDTA disodium), and buffering agents (citric acid, sodium citrate) that mediate between the colchicine active ingredient and the aqueous environment. These intermediaries protect colchicine from degradation by scavenging free radicals, chelating metal ions, and maintaining pH stability, thereby enabling oral liquid formulation while preserving stability.
Solution Approach 2:
The formulation employs a composite approach by combining colchicine with multiple excipients including sweeteners (sucralose), flavoring agents, preservatives (benzyl alcohol), and stabilizing agents in specific concentrations. This composite formulation creates a synergistic system where each component contributes to overall stability, palatability, and preservation, transforming the unstable colchicine into a stable oral liquid dosage form.
2Stability of the object's composition
If glycerin is added to the colchicine formulation, then viscosity and stability are improved, but photodegradation is accelerated
Solution Approach 1:
The patent introduces antioxidants (ascorbic acid at 0.01-0.1% and tocopherol at 0.01-0.05%) as intermediary substances that specifically counteract the photodegradation effect caused by glycerin. These antioxidants act as free radical scavengers that intercept degradation pathways initiated by light exposure in the presence of glycerin, thereby protecting colchicine while maintaining the beneficial viscous properties of glycerin.
Solution Approach 2:
The formulation converts the harmful photodegradation effect into a beneficial outcome by using chelating agents (EDTA disodium at 0.01-0.1%) that bind to metal ions which would otherwise catalyze degradation. The chelating agent transforms the potentially harmful interaction between glycerin and light into a controlled system where metal ion chelation prevents degradation cascades.
3Stability of the object's composition
If existing additives are used to prevent colchicine degradation, then stability is improved, but acceptability as oral excipients deteriorates
Solution Approach 1:
The patent changes the parameters of the stabilizing agents by selecting substances with appropriate concentrations and properties for oral administration. Instead of using high concentrations of industrial-grade stabilizers, the formulation uses low concentrations (0.01-0.1%) of food-grade antioxidants and chelating agents that meet pharmacopeial standards for oral products, thereby achieving stability while ensuring acceptability.
Solution Approach 2:
The formulation applies local quality by using different types of stabilizing agents for different protection mechanisms: antioxidants for oxidative degradation, chelating agents for metal ion-mediated degradation, and buffering agents for pH-related instability. Each excipient is selected with specific properties appropriate for its function while meeting oral administration requirements, creating a multi-layered protection system.
4Stability of the object's composition
If colchicine is administered as solid oral dosage form, then stability is maintained, but ease of administration and patient compliance deteriorate
Solution Approach 1:
The patent fundamentally changes the physical state parameter of colchicine from solid (tablet or capsule) to liquid form. This phase change enables the formulation to be administered orally in liquid dosage forms that are easier to swallow, can be adjusted for different age groups, and provide more flexible dosing options while maintaining stability through the use of protective excipients.
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 maintains colchicine stability at room temperature for extended periods, providing flexibility in dosage regimens and suitability for various patient populations, including geriatrics, while masking the bitter taste and preventing microbial growth.
Implementation Method 1
The buffering agent in some embodiments is about 0.12% (w/v) citric acid (anhydrous)
Implementation Method 2
In some embodiments the preservative is about 0.3% (w/v) of benzyl alcohol
Implementation Method 3
A stable oral liquid formulation of colchicine is developed using a pharmaceutically acceptable solvent system comprising water, glycols, buffering agents, sweeteners, flavoring agents, preservatives, and dyes
Data Source
AI summary
Oral liquid colchicine formulations are described herein. Methods of using the oral liquid colchicine formulations are also provided.