Propiverine Biphasic Release Matrix Using pH-Dependent Polymers
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Solution Overview
Problem
Current controlled release formulations of propiverine do not achieve a biphasic release profile with less than 50% release rate until 9 hours and not less than 85% release in 24 hours, and there is a need for a simple and industrially viable process to manufacture a dosage form with acceptable dissolution profiles.
Innovation Solution
A pharmaceutical composition comprising propiverine with a biphasic in vitro release profile is achieved using a combination of pH-dependent and hydrophilic polymers, along with pore-forming agents, specifically hydroxypropyl cellulose, hydroxypropylmethyl cellulose, lactose, and pH-dependent polymers like EUDRAGIT®, which control the release of propiverine over 24 hours, ensuring less than 50% release in the first 9 hours and more than 85% release by 24 hours in specific pH conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional controlled release formulations are used, then propiverine release is extended, but the desired biphasic release profile (less than 50% until 9 hours and not less than 85% in 24 hours) is not achieved
Solution Approach 1:
The patent uses a composite matrix formulation combining hydrophilic polymers (hydroxypropyl cellulose, hydroxypropylmethyl cellulose) with pH-dependent polymers (EUDRAGIT L 100, EUDRAGIT L 100-55) to create a multi-functional release system. This composite material structure enables the biphasic release profile by leveraging the different release mechanisms of each polymer component - the hydrophilic polymers provide initial controlled release while the pH-dependent polymers respond to intestinal pH to enhance release in the second phase.
Solution Approach 2:
The formulation incorporates pore-forming agents (lactose monohydrate, lactose spray-dried) that create a porous matrix structure. This porosity controls the diffusion pathways for propiverine release, allowing modulation of the release rate. The porous structure enables water penetration and drug dissolution while maintaining controlled release kinetics, contributing to achieving the target biphasic profile.
2Manufacturing precision
If complex manufacturing processes are used to achieve controlled release, then release profile is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent combines multiple release-controlling functions into a single matrix formulation layer, eliminating the need for multiple coating layers or complex multi-component systems. By integrating hydrophilic polymers, pH-dependent polymers, and pore-forming agents into one composite matrix, the formulation achieves biphasic release through a simplified manufacturing process suitable for standard tablet compression equipment.
Solution Approach 2:
The formulation exploits pH parameter changes in the gastrointestinal tract to trigger the second phase of release. The pH-dependent polymers remain relatively stable in gastric pH but dissolve or swell at intestinal pH levels, automatically triggering enhanced drug release without requiring external control mechanisms. This passive response to physiological parameter changes simplifies the manufacturing process.
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 composition provides a controlled release of propiverine with a biphasic profile, ensuring therapeutic levels are maintained for 24 hours, with less than 50% release in the first 9 hours and more than 85% release by 24 hours, as measured by USP Type I apparatus, effectively addressing the need for prolonged drug release.
Implementation Method 1
a combination of pH-dependent and hydrophilic polymers, along with pore-forming agents, specifically hydroxypropyl cellulose, hydroxypropylmethyl cellulose, lactose, and pH-dependent polymers like EUDRAGIT®, which control the release of propiverine over 24 hours
Implementation Method 2
a combination of pH-dependent and hydrophilic polymers, along with pore-forming agents, specifically hydroxypropyl cellulose, hydroxypropylmethyl cellulose, lactose
Implementation Method 3
a combination of pH-dependent and hydrophilic polymers, along with pore-forming agents, specifically hydroxypropyl cellulose, hydroxypropylmethyl cellulose, lactose
Data Source
Figure 1~2
AI summary
The present invention relates to controlled release pharmaceutical compositions for oral administration comprising propiverine or a pharmaceutically acceptable salt thereof. More specifically, the present invention relates to a pharmaceutical composition for oral administration exhibiting a biphasic in vitro release of the active ingredient, characterized as less than 50.0% release after nine hours and more than 85.0% release after 24 hours.