Dual-Release Midodrine Compositions for Extended Therapeutic Levels
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Solution Overview
Problem
Current immediate release formulations of midodrine hydrochloride require frequent dosing due to short half-lives, leading to fluctuations in blood pressure and decreased patient compliance, as they do not maintain effective plasma concentrations of desglymidodrine throughout the day.
Innovation Solution
A pharmaceutical composition with a dual-release profile, comprising a fast-release portion followed by an extended-release portion, designed to provide a relatively fast initial release and sustained release of midodrine or its metabolites over several hours, maintaining effective plasma concentrations for extended periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If immediate release formulations are used, then rapid absorption and onset of action are achieved, but frequent dosing is required leading to blood pressure fluctuations and decreased patient compliance
Solution Approach 1:
The patent segments the drug release into two distinct portions: a first release portion (immediate release) providing rapid absorption for quick onset of action, and a second release portion (extended release) providing sustained release for prolonged therapeutic effect. This segmentation resolves the contradiction by allowing both rapid initial absorption and extended duration of action without requiring frequent dosing.
Solution Approach 2:
The patent changes the release rate parameter over time through the dual-release formulation. The first release portion provides a high initial release rate for rapid absorption, while the second release portion maintains a lower, sustained release rate for extended therapeutic effect. This parameter change allows the formulation to achieve both rapid onset and prolonged duration without frequent dosing.
2Reliability
If frequent dosing is administered to maintain effective plasma concentrations, then therapeutic effect is maintained, but patient compliance decreases due to dosing frequency
Solution Approach 1:
The patent achieves continuity of useful action by designing a dual-release formulation where the first release portion provides immediate therapeutic effect and the second release portion extends the therapeutic effect over a prolonged period. This continuous release profile maintains effective plasma concentrations without requiring frequent dosing, thereby improving patient compliance while ensuring reliable therapeutic effect.
3Duration of action of moving object
If extended release formulations are used, then dosing frequency is reduced and compliance improves, but initial onset of action is delayed
Solution Approach 1:
The patent segments the release profile into a first release portion that provides immediate release for rapid onset of action, followed by a second release portion that provides extended release for prolonged therapeutic effect. This segmentation resolves the contradiction by ensuring both rapid initial onset and extended duration of action in a single formulation.
Solution Approach 2:
The first release portion acts as a preliminary action that provides immediate therapeutic effect upon administration, establishing rapid onset of action. This is followed by the second release portion that extends the therapeutic effect, thereby achieving both rapid onset and prolonged duration without requiring multiple separate formulations.
Data Source
AI summary
This disclosure provides pharmaceutical compositions comprising midodrine, a pharmaceutically acceptable salt thereof, desglymidodrine, or a pharmaceutically acceptable salt thereof, that can be administered to a human subject in need thereof. The disclosure also provides pharmaceutical compositions for treatment of orthostatic hypotension that can be administered once or twice a day.