Multilayered Microparticles for Acid-Labile Drug Stability
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Solution Overview
Problem
Current oral pharmaceutical compositions face challenges in maintaining stability and controlled release of acid-labile and gastric mucosa-aggressive compounds, particularly when administered in liquid form, as they are prone to degradation in acidic environments and have issues with patient compliance due to swallowing difficulties and variability in gastric conditions.
Innovation Solution
Development of multilayered controlled-release microparticles with an outermost coating layer containing a hydrophilic gastro-soluble component and a hydrophobic/insoluble component, which is soluble in gastric fluid, allowing the microparticles to maintain stability in liquid media and release the active compound effectively in the intestine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If acid-labile compounds are delivered in the acidic environment of the stomach, then oral administration is achieved, but the compounds are susceptible to degradation prior to reaching the intestine
Solution Approach 1:
The microparticle is divided into multiple functional layers: a core containing the acid-labile compound, an enteric coating layer that protects the core from acid, and an outermost coating layer that provides additional protection in liquid media. This segmentation allows the compound to survive gastric acid while enabling oral administration.
Solution Approach 2:
The microparticle uses a composite structure with different materials for different functions: the enteric coating layer uses pH-sensitive polymers that resist acid, while the outermost coating layer uses hydrophobic/insoluble components that resist liquid media. This composite approach simultaneously achieves oral administrability and compound stability.
2Reliability
If pharmaceutically active compounds are shielded from gastric environment for intestinal release, then compound stability is improved, but controlled-release properties are required
Solution Approach 1:
The enteric coating layer is designed to change its properties based on pH parameters - it remains intact in acidic gastric environment (pH 1-3) but dissolves in intestinal pH (pH 6-8). This parameter-based switching provides controlled release without complex mechanisms.
3Reliability
If multilayered microparticles are designed for controlled release, then compound protection is achieved, but stability in liquid media becomes challenging
Solution Approach 1:
The outermost coating layer acts as a flexible protective shell that is soluble in gastric fluid but provides barrier protection in liquid media. This thin film structure maintains controlled-release functionality while protecting against premature dissolution in liquid formulations.
4Reliability
If enteric coating layer is used to protect from acid, then compound degradation is prevented, but solubility in liquid media may be affected
Solution Approach 1:
The outermost coating layer serves as an intermediary between the enteric coating layer and the liquid media. It allows the enteric layer to maintain its acid-protection function while the outermost layer interfaces with liquid media, preventing premature dissolution through its hydrophobic/insoluble properties.
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 multilayered microparticles remain stable for extended periods in liquid form and ensure controlled release of the active compound, avoiding degradation in acidic environments and improving patient compliance by allowing targeted and prolonged therapeutic effects.
Implementation Method 1
an outmost external protection coating layer surrounding said controlled-release layer and comprising a mixture of (a) a hydrophilic gastro-soluble component which is insoluble in aqueous media at a pH between 6.5 and 7.5 and (b) a hydrophobic and/or insoluble component, wherein said outmost external protection coating layer is soluble in gastric fluid
Implementation Method 2
a hydrophobic and/or insoluble component chosen in the group consisting of glycerides, wax, magnesium stearate, fatty alcohol, ethyl cellulose, copolymer based on ethyl acrylate and methyl methacrylate, silicone and stearic acid
Data Source
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AI summary
The present invention concerns control led-release multilayer microparticle containing a pharmaceutically active compound, said microparticle being intended for oral administration or direct administration in the stomach in the form of a liquid pharmaceutical composition. It concerns also the liquid pharmaceutical composition containing it, a kit for the preparation of said liquid pharmaceutical composition, a pharmaceutical solid composition intended to be reconstituted in the form of said liquid composition and a process of preparation of said liquid composition.