Colchicine Sustained Release Microspheres for Once-Daily Dosing
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Solution Overview
Problem
Current colchicine formulations for treating cardiovascular diseases and inflammatory disorders require multiple daily doses, leading to poor patient compliance and increased side effects due to high peak drug levels.
Innovation Solution
A sustained release formulation of colchicine, characterized by a retarding agent and pharmaceutically acceptable excipients, is administered once daily, providing a steady release of colchicine over an extended period.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If colchicine is administered multiple times daily to maintain therapeutic levels, then therapeutic efficacy is improved, but patient compliance deteriorates and side effects increase due to high peak concentrations
Solution Approach 1:
The patent segments the total daily colchicine dose into multiple smaller microspheres, each releasing drug at a controlled rate. This segmentation allows the drug to be delivered continuously over 24 hours through a single administered unit, eliminating the need for multiple dosing events while maintaining therapeutic levels.
Solution Approach 2:
The patent applies preliminary action by pre-encapsulating the colchicine in sustained-release microspheres before administration. The drug release kinetics are predetermined during formulation, ensuring that the drug is released at the desired rate over 24 hours without requiring multiple dosing events from the patient.
2Reliability
If colchicine is administered multiple times daily to maintain therapeutic levels, then therapeutic efficacy is improved, but side effects worsen due to high peak drug concentrations
Solution Approach 1:
The total dose is segmented into numerous microspheres (typically 100-10,000 per tablet) that release colchicine individually at a controlled rate. This segmentation prevents sudden release of large amounts of drug, thereby avoiding high peak concentrations that cause side effects while maintaining continuous therapeutic levels.
Solution Approach 2:
The patent changes the release rate parameter of colchicine from rapid (immediate release) to slow and controlled (sustained release over 24 hours). This parameter change in drug release kinetics reduces peak concentrations to below toxic thresholds while maintaining therapeutic efficacy through continuous low-level delivery.
3Speed
If immediate release colchicine formulations are used, then rapid therapeutic effect is achieved, but patient compliance deteriorates due to multiple daily dosing requirements
Solution Approach 1:
The patent implements continuity of useful action by designing microspheres that release colchicine continuously over 24 hours from a single administered tablet. This continuous release maintains therapeutic drug levels throughout the dosing interval, eliminating the gaps between doses that would otherwise require frequent redosing.
Data Source
AI summary
Pharmaceutical compositions of colchicine for once-a-day oral administration are provided. The compositions comprise a combination pill which includes (a) a therapeutically effective amount of a composition comprising no more than about 0.6 total mg of colchicine, (b) an amount of a second compound, said second compound being a colchicine-compatible statin; and (c) an amount of a third compound, said third compound being at least one of: (i) a colchicine-compatible SGLT2 inhibitor; and/or (ii) a colchicine-compatible GLP-1 receptor agonist colchicine-compatible; wherein said first compound, said second compound, and said third compound are administered together in the pill with a pharmaceutically acceptable carrier. Methods of treating or reducing a risk of both a cardiovascular event and high blood sugar levels in mammalian subjects comprising the administration of the novel compositions disclosed herein are also provided.