Thiocolchicoside Sustained Release Formulation with Rate Controlling Polymers

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Solution Overview

Problem

Conventional thiocolchicoside formulations exhibit rapid absorption and high initial plasma concentration followed by rapid decline, leading to transient dose dumping and fluctuations, which are detrimental to therapeutic efficacy and patient compliance, necessitating a sustained release formulation that maintains constant drug levels and reduces side effects.

Innovation Solution

A sustained release pharmaceutical formulation containing thiocolchicoside and at least one rate controlling polymer, such as glyceryl behenate, for oral administration, which releases the drug in a controlled manner over an extended period, preventing dose dumping and maintaining requisite blood levels for once daily or twice daily dosing, and utilizing ammonio methacrylate copolymer for pH-independent release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional immediate release formulations of thiocolchicoside are used, then the drug is rapidly absorbed and achieves high initial plasma concentration, but this leads to rapid decline in plasma levels, transient dose dumping, and fluctuations in drug concentration

Engineering Contradiction:
Improveabsorption speedVSAvoidplasma concentration stability
Core Design Contradiction:
SpeedVSStability of the object's composition

Solution Approach 1:

The patent changes the release rate parameter of thiocolchicoside from rapid (immediate release) to controlled/sustained release by incorporating rate-controlling polymers such as hydroxypropyl methylcellulose (HPMC), ethyl cellulose, or carboxymethyl cellulose. This parameter change transforms the plasma concentration profile from fluctuating high-peak levels to stable, sustained levels within the therapeutic window, resolving the contradiction between rapid absorption and concentration stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces rate-controlling polymers as intermediary substances that mediate between the rapidly absorbed thiocolchicoside and the bloodstream. These polymers form a controlled release matrix that gradually releases the drug, acting as a buffer to prevent both rapid peak formation and subsequent sharp declines, thereby maintaining stable plasma concentrations.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If conventional formulations are administered multiple times daily to maintain therapeutic levels, then plasma concentration fluctuations are addressed, but patient compliance deteriorates due to frequent dosing requirements

Engineering Contradiction:
Improvetherapeutic level maintenanceVSAvoidpatient compliance
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent implements continuous controlled release of thiocolchicoside over extended periods (24 hours or more) through the use of sustained-release formulations. This continuous release mechanism eliminates the need for multiple daily dosing while maintaining therapeutic plasma levels, thereby improving patient compliance without compromising therapeutic level maintenance.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent creates a dynamic release system where the formulation adapts to maintain constant plasma concentrations over time. The rate-controlling polymers provide a sustained release profile that dynamically adjusts drug release to match metabolic elimination rates, enabling once-daily or twice-daily dosing while maintaining therapeutic efficacy.

Inventive Principle:
Principle #15Dynamics

3Speed

If high initial plasma concentration is achieved through rapid absorption, then immediate therapeutic effect is obtained, but side effects increase due to transient dose dumping

Engineering Contradiction:
Improveonset of actionVSAvoidside effects from dose dumping
Core Design Contradiction:
SpeedVSObject-generated harmful factors

Solution Approach 1:

The patent applies partial action by releasing only the necessary amount of thiocolchicoside at each time point to maintain therapeutic levels, rather than releasing the entire dose rapidly. The sustained-release formulation provides gradual drug release at controlled rates, preventing the excessive initial concentration that causes dose dumping and associated side effects, while still achieving therapeutic effects.

Inventive Principle:
Principle #16Partial or excessive action

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 a controlled and sustained release of thiocolchicoside, maintaining therapeutic effects for a longer duration, improving patient compliance and reducing side effects by maintaining constant plasma concentrations, and ensuring repeatable and pH-independent release profiles.

Implementation Method 1

sustained release pharmaceutical formulation containing thiocolchicoside and at least one rate controlling polymer

Methodology Applied
Scientific EffectSustained release:

Implementation Method 2

releases the drug in a controlled manner over an extended period

Methodology Applied
Scientific EffectControlled release:

Implementation Method 3

utilizing ammonio methacrylate copolymer for pH-independent release

Methodology Applied
Scientific EffectpH-independent release:

Data Source

PatentEP2848259B1Sustained release pharmaceutical formulations of Thiocolchicoside
Publication Date: 2016.03.23 SANOVEL ILAC SANAYI & TICARET ANONIM SIRKETI
  • EP2848259B1 patent drawingFigure 1
  • EP2848259B1 patent drawing

AI summary

Present invention relates to novel sustained release pharmaceutical formulations containing an effective amount of thiocolchicoside or pharmaceutically acceptable salts thereof for oral administration with myorelaxant activity.