Extended Release Thiocolchicoside Tablets for Stable Plasma Levels
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Solution Overview
Problem
Conventional thiocolchicoside tablets taken twice daily result in deep plasma concentration fluctuations due to the active metabolite's short elimination half-life, leading to low plasma levels at dosing times and increased frequency of deep releases, which can be inconvenient for patients.
Innovation Solution
Development of extended release tablets containing a combination of immediate and extended release components, utilizing cellulose derivatives like hydroxypropyl methylcellulose, to maintain stable plasma concentrations by releasing 35-65% of thiocolchicoside immediately and the remaining 55-56% over 5 hours or more, providing a single daily dosing regimen equivalent to conventional twice-daily administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional immediate release tablets are administered twice daily, then the initial plasma concentration is achieved quickly, but deep plasma concentration fluctuations occur with low levels at dosing times
Solution Approach 1:
The tablet is divided into two distinct parts: an immediate release part containing 35-45% of thiocolchicoside and an extended release part containing 55-65% of thiocolchicoside. This segmentation allows the immediate release part to rapidly achieve therapeutic plasma concentrations while the extended release part maintains stable levels over 24 hours, eliminating the deep fluctuations seen with conventional twice-daily dosing
Solution Approach 2:
The extended release polymer matrix ensures continuous drug release over 24 hours, maintaining therapeutic plasma concentrations without the deep declines that occur between doses in conventional regimens. This continuous action provides stable muscle relaxation efficacy throughout the dosing interval
2Reliability
If conventional tablets are taken twice daily, then plasma concentration is maintained, but dosing frequency and patient convenience are reduced
Solution Approach 1:
By segmenting the tablet into immediate and extended release components, a single daily dose achieves both rapid initial effect and sustained 24-hour coverage, eliminating the need for twice-daily administration while maintaining reliable plasma concentrations
Solution Approach 2:
The invention changes the release rate parameter by using different polymer matrices with controlled porosity and degradation rates, allowing one dose to provide sustained release over 24 hours while maintaining therapeutic levels
3Stability of the object's composition
If extended release formulation is used, then plasma concentration stability is improved, but the immediate effect onset may be delayed
Solution Approach 1:
The segmented tablet design with immediate release part (35-45% drug content) ensures rapid onset of action within 1-2 hours, while the extended release part (55-65% drug content) simultaneously provides stable long-term concentrations, eliminating the delay issue
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 extended release formulation stabilizes plasma concentrations, reducing deep releases and providing sustained efficacy, making it more convenient for patients with a single daily dose while maintaining bioequivalence to conventional tablets.
Implementation Method 1
The tablet developed consists of the separate parts, one of which provides immediate release and the other provides extended release. Extended release part is the matrix type formulation. Cellulose derivative polymers are used in matrix type of formulation.
Implementation Method 2
Preferred cellulose derivative used as polymer is hydroxypropyl methylcellulose and more preferably, hydroxypropyl methylcellulose 4000 cps commercially known as Methocel K4M CR.
Data Source
Figure 1~2
AI summary
Present invention is related to extended release pharmaceutical composition containing 8 to 16 mg thiocolchicoside with once a day dosage regime. The composition contains a polymer which controls the release of thiocolchicoside. 35 to 65% of thiocolchicoside in the formulation is released at the first hour in 0.1 N hydrochloric acid medium. The composition is equivalent to the conventional tablets taken twice daily.