Thiocolchicoside Dual-Phase Formulation for Stable Plasma
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional immediate release formulations of thiocolchicoside require frequent dosing (three to four times daily), leading to fluctuations in blood plasma concentrations and potential side effects, and are inconvenient for patients, while sustained release formulations face challenges in maintaining therapeutic effects and physical stability due to tablet hardness and compression force.
Innovation Solution
A pharmaceutical formulation comprising an immediate release phase and a sustained release phase using glyceryl behenate as a rate-controlling polymer, which maintains stable plasma concentrations for extended periods, allowing for once or twice daily dosing, and is independent of tablet hardness, thereby improving patient compliance and physical properties of the tablets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If immediate release formulations of thiocolchicoside are used, then rapid absorption and immediate therapeutic effect are achieved, but frequent dosing (three to four times daily) is required leading to fluctuations in blood plasma concentrations and reduced patient compliance
Solution Approach 1:
The patent applies a dual-phase release system that dynamically adjusts drug release rates: an immediate release phase provides rapid initial absorption for quick therapeutic effect, while a sustained release phase maintains stable plasma concentrations over extended periods. This dynamic release profile eliminates the need for frequent dosing while preserving rapid onset benefits.
Solution Approach 2:
The sustained release phase ensures continuous therapeutic action by maintaining steady plasma concentrations of thiocolchicoside over 12-24 hours. This continuous release mechanism eliminates the fluctuations associated with immediate release formulations and extends the duration of therapeutic effect without requiring repeated dosing.
2Duration of action of stationary object
If sustained release formulations are used, then dosing frequency is reduced and plasma concentrations are stabilized, but tablet hardness must be carefully controlled to maintain both physical stability and drug release properties
Solution Approach 1:
The patent optimizes specific formulation parameters including glyceryl behenate content (10-30%), compression force (5-15 tons), and granule particle size (0.5-1.0 mm) to achieve the desired balance between tablet physical stability and sustained drug release. These parameter changes enable extended duration of action while maintaining manufacturable tablet properties.
Solution Approach 2:
The formulation uses a composite approach combining multiple excipients with distinct functions: glyceryl behenate as a rate-controlling polymer for sustained release, microcrystalline cellulose for structural integrity, and starch for disintegration. This composite material system achieves both extended duration of action and adequate tablet physical properties.
3Strength
If compression force is increased to improve tablet physical properties, then tablet hardness and resistance to breakage are improved, but release of active agent decreases
Solution Approach 1:
Glyceryl behenate acts as an intermediary substance that mediates between compression force and drug release. This rate-controlling polymer forms a matrix structure that maintains tablet integrity under compression while simultaneously controlling the diffusion and release of thiocolchicoside, ensuring both tablet strength and adequate drug release are achieved.
Solution Approach 2:
The granulated formulation creates a porous matrix structure through the granulation process that allows drug release pathways to be maintained even under compression. The porous structure of the glyceryl behenate-microcrystalline cellulose matrix enables drug diffusion while providing mechanical strength to the tablet.
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 achieves stable plasma concentrations of thiocolchicoside for 12-24 hours, reducing dosing frequency and side effects, and maintains therapeutic effects while being resistant to capping, aberration, or breakage, enhancing patient compliance and tablet stability.
Implementation Method 1
sustained release phase comprising glyceryl behenate as rate controlling polymer
Implementation Method 2
glyceryl behenate as rate controlling polymer, which maintains stable plasma concentrations for extended periods
Implementation Method 3
increase of the tablet hardness causes the decrease of the release of the active agent. Since the hardness of the tablets increased with the increased compression force
Implementation Method 4
adjust the hardness of the sustained release tablet carefully by applying the sufficient compression force
Data Source
Figure 1~2
Figure 3~4
AI summary
The present invention relates to a sustained release pharmaceutical formulation comprising immediate release phase, and sustained release phase comprising glyceryl behenate as rate controlling polymer, wherein each of phases comprising thiocolchicoside or a pharmaceutically acceptable salt thereof