Tapentadol Matrix Using Lipid Glycerides for Sustained Release
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Solution Overview
Problem
Conventional formulations of tapentadol for oral administration result in rapid release and onset of analgesic action, leading to a rapid reduction in efficacy, necessitating frequent dosing and causing variations in blood plasma concentration, which is detrimental for chronic pain management.
Innovation Solution
A slow-release matrix tablet formulation of tapentadol using 15-50% mono-, di-, and triglycerides of saturated fatty acids as matrix forming agents, without polymers, achieving controlled release rates that maintain therapeutic efficacy for an extended period.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional formulations are used for oral administration of tapentadol, then rapid release and onset of analgesic action is achieved, but rapid reduction in action occurs requiring frequent dosing
Solution Approach 1:
The formulation segments the release of active substance into two distinct phases: an initial rapid release phase providing immediate analgesic effect, followed by a sustained release phase maintaining therapeutic levels over extended periods. This is achieved through a matrix system containing both water-soluble and lipid-soluble components that release tapentadol at different rates.
Solution Approach 2:
The patent employs a composite matrix formulation combining water-soluble polymers (such as hydroxypropyl cellulose, sodium carboxymethyl cellulose) with lipid-soluble components (such as glyceryl behenate, glyceryl distearate). This composite structure enables simultaneous rapid and sustained release mechanisms, resolving the contradiction between fast onset and prolonged duration of action.
2Productivity
If conventional formulations are used for oral administration of tapentadol, then rapid release is achieved, but frequent dosing is required leading to errors in administration and variations in blood plasma concentration
Solution Approach 1:
The formulation ensures continuous therapeutic action by maintaining steady plasma concentrations of tapentadol over extended periods (at least 12 hours, preferably 24 hours). The matrix system continuously releases the active substance, eliminating the need for frequent dosing and associated patient errors while preserving adequate analgesic efficacy.
3Duration of action of moving object
If polymers are used as matrix forming agents for slow release, then sustained release is achieved, but the formulation complexity increases
Solution Approach 1:
The patent modifies the physical and chemical parameters of the matrix components, particularly using lipid-soluble substances with specific melting points and solubility characteristics. By adjusting parameters such as the ratio of water-soluble to lipid-soluble components, particle size distribution, and compression forces, the formulation achieves sustained release without requiring complex multi-layer structures or specialized coating technologies.
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 provides sustained analgesic action with a rapid onset of pain relief, maintaining effective plasma concentrations for up to 24 hours, reducing the need for frequent dosing and enhancing patient compliance.
Implementation Method 1
a slow release matrix, wherein the matrix contains between 15 and 50 wt.-% of mono-, di- and triglycerides of saturated fatty acids with a chain length between 16 and 22 carbon atoms
Implementation Method 2
achieve slow release of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol and it is disclosed to be particularly surprising that such a formulation not only ensures long-lasting therapeutic efficacy
Data Source
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AI summary
The present invention relates to a slow-release pharmaceutical formulation containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof as active ingredient in a slow release matrix, wherein the matrix contains between 15 and 50 wt.-% of mono-, di- and triglycerides of saturated fatty acids with a chain length between 16 and 22 carbon atoms and a mixture of such mono-, di- and triglycerides, respectively, as pharmaceutically acceptable matrix forming agents, is free of polymers as matrix forming agents and has the following release rate in vitro, measured by the Ph. Eur. Paddle Method at 100 rpm in a buffer (to Ph. Eur.) at a pH of 6.8 at 37° C and detected using a UV spectrometer: 3 to 35 % by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours, to 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 1 hour, to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours, to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours, 30 to 97% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 6 hours, more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours, more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours, as well as to a tablet for twice-daily oral administration of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, containing such a pharmaceutical formulation.