Oral Tablet with Segmented Immediate and Modified Release Layers
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Solution Overview
Problem
The combination of tamsulosin and solifenacin in a single formulation results in a decreased dissolution rate and maximum percentage of solifenacin dissolution, affecting bioavailability and pharmacological effects, as the water-soluble solifenacin is incorporated into the modified release portion containing a hydrogel-forming polymer, leading to unexpected delays in drug release.
Innovation Solution
A tablet comprising a modified release portion with tamsulosin and a hydrogel-forming polymer, and an immediate release portion with solifenacin and hydrophilic substances like D-mannitol, polyethylene glycol, or polyvinylpyrrolidone, where the immediate release portion disintegrates and dissolves before the modified release portion forms a gel, ensuring 70% or more of solifenacin dissolves within 15 minutes and 90% within 60 minutes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If a single formulation contains both modified release tamsulosin and immediate release solifenacin, then the number of formulations is reduced and dosing compliance is improved, but the dissolution rate and maximum percentage of solifenacin dissolution decrease
Solution Approach 1:
The tablet is divided into two distinct layers: a modified release layer containing tamsulosin and a hydrogel-forming polymer, and an immediate release layer containing solifenacin and hydrophilic substances. This segmentation allows each drug to release according to its intended profile without interfering with the other, resolving the contradiction between combined formulation convenience and maintained dissolution performance
Solution Approach 2:
A hydrophilic substance layer acts as an intermediary between the modified release and immediate release portions. This intermediate layer prevents water from directly penetrating into the modified release portion too quickly, while still allowing the immediate release portion to dissolve rapidly. The hydrophilic substance mediates the water distribution to ensure solifenacin releases immediately without being incorporated into the hydrogel matrix
2Device complexity
If solifenacin is placed in the modified release portion with hydrogel-forming polymer, then a single layered structure is simplified, but water-soluble solifenacin is incorporated into the gel and release is delayed
Solution Approach 1:
Instead of a single layered structure, the formulation uses a multi-layer structure with distinct zones: modified release layer, hydrophilic substance layer, and immediate release layer. This segmentation prevents water-soluble solifenacin from being incorporated into the hydrogel matrix by creating a physical barrier (the hydrophilic substance layer) that controls water flow and drug release timing
Solution Approach 2:
The solifenacin is extracted from the modified release portion and placed in a separate immediate release layer. This extraction ensures that the water-soluble solifenacin does not get incorporated into the hydrogel-forming polymer matrix, thereby preventing delayed release and maintaining rapid dissolution characteristics
3Reliability
If the immediate release portion dissolves rapidly, then bioavailability of solifenacin is maintained, but the modified release portion may not form proper gel structure
Solution Approach 1:
The hydrophilic substance layer serves as an intermediary that manages water distribution between the two functional layers. It allows sufficient water to reach the immediate release portion for rapid dissolution and high bioavailability, while simultaneously providing controlled water penetration to the modified release portion to allow proper gel structure formation without compromising either function
Solution Approach 2:
Different regions of the tablet have different water permeability and dissolution characteristics. The immediate release layer has high water permeability for rapid dissolution, while the modified release layer has controlled water permeability for proper gel formation. The hydrophilic substance layer creates a gradient of water distribution, ensuring each portion receives the appropriate amount of water for its intended function
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
This configuration maintains drug release rates similar to single drug formulations, enhancing bioavailability and pharmacological effects, while improving drug dosing compliance by reducing the number of formulations needed.
Implementation Method 1
a modified release portion comprising tamsulosin or a pharmaceutically acceptable salt thereof, and a polymer which forms a hydrogel
Implementation Method 2
an immediate release portion comprising solifenacin or a pharmaceutically acceptable salt thereof and at least one hydrophilic substance from the group consisting of D-mannitol, maltose, polyethylene glycol, and polyvinylpyrrolidone
Data Source
Figure 1~2
Figure 3
AI summary
The present invention relates to a pharmaceutical composition for oral administration comprising a modified release portion containing tamsulosin or a pharmaceutically acceptable salt thereof, and an immediate release portion containing solifenacin or a pharmaceutically acceptable salt thereof and a hydrophilic substance. In the pharmaceutical composition, the dissolution rate of each drug (in particular, solifenacin contained in the immediate release portion) is similar to those of the current single drug formulations, and the maximum percentage of drag dissolution of each drug (in particular, solifenacin contained in the immediate release portion) is 90% or more. Therefore, the pharmaceutical composition is a single formulation (i.e., a combined formulation) with a bioavailability equivalent to those of the current single drug formulations.