Propiverine Enteric Coating for Controlled Release
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Solution Overview
Problem
Current pharmaceutical formulations of propiverine, a BCS Class III drug, face challenges in achieving controlled release and optimal bioavailability due to its low permeability and high solubility, with existing technologies not effectively managing the drug's release profile in the gastrointestinal tract.
Innovation Solution
A controlled-release matrix form tablet design using Eudragit S100 and Eudragit L100-55 as pH-dependent polymers, with an enteric coating comprising 0.5% to 2.5% by weight of the core tablet, which ensures negligible dissolution at low pH levels in the stomach and rapid dissolution in the upper bowel, allowing for prolonged release of propiverine in the small intestine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If immediate release formulation is used, then rapid absorption and onset of action is achieved, but bioavailability is limited to 40.5% and therapeutic effects are short-lived
Solution Approach 1:
The tablet is segmented into core and coating layers, where the core contains the drug and the coating controls release. The enteric coating segments the release process by preventing dissolution in stomach (low pH) and enabling dissolution in intestine (high pH), thereby improving bioavailability while maintaining rapid absorption when the coating dissolves.
Solution Approach 2:
The formulation uses pH-dependent polymers (Eudragit S100 and Eudragit L100-55) that change their solubility parameters based on pH. The coating remains intact at gastric pH but dissolves at intestinal pH, transforming the release profile from immediate to controlled while enhancing bioavailability to 60.8%.
2Reliability
If modified release formulation is used, then bioavailability is improved to 60.8%, but the release profile is not optimally controlled in the gastrointestinal tract
Solution Approach 1:
The formulation uses a composite coating system combining two different pH-dependent polymers: Eudragit S100 (soluble at pH ≥ 7.0) and Eudragit L100-55 (soluble at pH ≥ 5.5). This composite approach provides more precise control over the release profile by leveraging the complementary dissolution characteristics of both polymers, ensuring optimal bioavailability and controlled release in the gastrointestinal tract.
3Object-affected harmful factors
If enteric coating is applied, then dissolution in stomach is prevented, but dissolution in upper bowel must be rapid for effective absorption
Solution Approach 1:
The enteric coating exhibits dynamic behavior by changing its dissolution properties in response to pH changes along the gastrointestinal tract. The coating remains stable and prevents dissolution in the acidic stomach environment, then dynamically dissolves rapidly when it reaches the higher pH environment of the upper bowel, ensuring both protection and rapid absorption.
Solution Approach 2:
The pH-dependent polymers in the coating undergo a phase transition from insoluble to soluble state as pH increases from gastric to intestinal levels. This phase transition enables the coating to prevent dissolution in stomach while allowing rapid dissolution in upper bowel, effectively resolving the contradiction between protection and absorption.
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 biphasic in vitro release characteristics, with propiverine being effectively released over 24 hours, maintaining bioequivalence within the 80-125% confidence interval, ensuring stable and prolonged therapeutic effects for treating overactive bladder and urinary incontinence.
Implementation Method 1
Eudragit S100 and Eudragit L100-55 as pH-dependent polymers, with an enteric coating comprising 0.5% to 2.5% by weight of the core tablet, which ensures negligible dissolution at low pH levels in the stomach
Implementation Method 2
rapid dissolution in the upper bowel, allowing for prolonged release of propiverine in the small intestine
Implementation Method 3
The formulation achieves biphasic in vitro release characteristics, with propiverine being effectively released over 24 hours
Data Source
AI summary
The present invention relates to controlled release pharmaceutical compositions for oral administration comprising propiverine or a pharmaceutically acceptable salt thereof. Particularly, the present invention relates to a pharmaceutical composition for oral administration with an enteric coating with an amount of the range between 0.5% to 2.5% by weight of core tablet.