Enteric-Coated Dosage Form With Alkaline Layer for pH 3-5.5 Release
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Solution Overview
Problem
Existing dosage forms fail to effectively release biologically active ingredients at pH values between 3 and 5.5, which is crucial for immediate action after stomach passage.
Innovation Solution
A dosage form comprising a core with a biologically active ingredient, an intermediate coating layer containing an alkaline agent, and an enteric coating layer, where the ratio of alkaline agent to enteric polymer is 5 to 95%, ensuring controlled release at pH 3 to 5.5.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the dosage form is designed for release at higher pH values, then the enteric coating provides protection in acidic stomach environment, but the drug cannot be released effectively at pH values between 3 and 5.5 which is crucial for optimal drug delivery after stomach passage
Solution Approach 1:
The coating system is divided into two distinct functional layers: an inner enteric coating layer that protects against acid dissolution and an outer pH-triggered release layer that activates at pH 3-5.5. This segmentation allows each layer to perform its specific function optimally, with the inner layer providing acid protection and the outer layer enabling controlled release at the desired pH range after stomach passage.
Solution Approach 2:
Different regions of the coating system have different pH responsiveness characteristics. The inner enteric coating layer is designed to remain stable in acidic conditions (pH < 3), while the outer layer is specifically formulated to trigger drug release at pH values between 3 and 5.5. This local differentiation of pH-triggered properties enables the system to protect the drug in the stomach while releasing it effectively in the post-stomach environment.
2Stability of the object's composition
If the dosage form provides stability at pH 3, then the biologically active ingredient is protected from degradation, but the release rate may be delayed beyond the optimal 45-minute window
Solution Approach 1:
The outer coating layer is pre-formulated with pH-triggered properties that are activated specifically when the dosage form reaches pH values between 3 and 5.5. This preliminary preparation of the release mechanism ensures that once the pH threshold is crossed, the drug releases rapidly within 45 minutes or less, optimizing both stability during transit and release speed upon activation.
Solution Approach 2:
The system utilizes pH as the triggering parameter to control the transition from stable stored state to rapid release state. The outer coating layer is designed with specific pH-responsive properties that remain inactive at low pH (providing stability) and activate at pH 3-5.5 (providing rapid release). This parameter-based control allows the system to achieve both stability and fast release by changing the environmental pH condition.
3Stability of the object's composition
If an alkaline agent is added to the intermediate coating layer to provide pH buffering, then the stability at pH 3 is improved, but the complexity of the coating system increases
Solution Approach 1:
The outer coating layer serves multiple functions simultaneously: it acts as a pH-triggered release layer, provides a buffering zone to stabilize pH between 3 and 5.5, and controls the timing of drug release. By making this single layer multi-functional, the system achieves pH stability and controlled release without requiring separate dedicated layers for each function, thereby reducing overall system complexity.
Solution Approach 2:
The pH buffering function is merged with the outer coating layer that is already designed for pH-triggered release. Instead of adding a separate buffering layer, the outer layer is formulated to perform both functions: triggering release at pH 3-5.5 and providing pH stabilization. This merging of functions into a single layer simplifies the overall coating system structure while maintaining the required stability.
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 dosage form achieves 10% or less release at pH 1.2 and 50% or more release at pH 3 to 5.5 within 45 minutes, maintaining stability of the active ingredient at pH 3 for 2 hours.
Implementation Method 1
The pH buffering properties of subcoating layer may be further strengthened by introducing substances chosen from a group of compounds usually used in antacid formulations such as, for instance, magnesium oxide, hydroxide or carbonate, aluminium or calcium hydroxide, carbonate or silicate
Implementation Method 2
The object of U.S. Pat. No. 4,786,505 is to provide an enteric coated dosage form of omeprazole, which is resistant to dissolution in acid media and which dissolves rapidly in neutral to alkaline media
Implementation Method 3
which dissolves rapidly in neutral to alkaline media
Data Source
AI summary
A dosage form contains a) a core, containing a biologically active ingredient, which is stable to a degree of at least 95% at a pH of 3 for 2 hours at 22° C.; b) an intermediate coating layer (ICL) onto or above the core, containing an alkaline agent; and c) an enteric coating layer (ECL) onto or above the intermediate coating layer, containing an enteric polymer. The relation in percent of the alkaline agent in the ICL to the enteric polymer in the ECL is 5 to 95% when calculated by the formula:quantity of alkaline agent in grams in the ICL×100(quantity of alkaline agent in grams in the ICL+quantity of enteric polymer in grams in the ECL).