Multilayer Microparticle Coating for Stable Liquid Controlled Release
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Solution Overview
Problem
Existing oral pharmaceutical compositions face challenges in maintaining the stability and controlled release of acid-labile compounds and gastric mucosa-aggressive compounds in liquid formulations, particularly for patients with swallowing difficulties, as they degrade in acidic environments and fail to provide sustained release in the intestines.
Innovation Solution
A multilayered microparticle design with an outer coating layer comprising a hydrophilic gastro-soluble component insoluble at pH 6.5-7.5 and a hydrophobic component protects the microparticles in liquid media, ensuring stability and controlled release in the gastrointestinal tract.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If acid-labile compounds are administered orally, then the compounds can be delivered to the gastrointestinal tract, but they degrade in the acidic stomach environment before reaching the intestine
Solution Approach 1:
The microparticle is divided into multiple functional layers: an inner core containing the acid-labile compound, an intermediate coating layer providing controlled release, and an outer enteric coating layer protecting against acid degradation. This segmentation allows each layer to perform its specific function independently, solving the contradiction between oral administration and compound stability.
Solution Approach 2:
The enteric coating layer acts as an intermediary barrier between the acid-labile compound and the acidic stomach environment. This protective layer prevents direct contact between the compound and acid, allowing the compound to remain stable until it reaches the intestine, thus resolving the stability issue while maintaining oral administration feasibility.
2Ease of operation
If gastric mucosa-aggressive compounds are administered orally, then the compounds can be delivered to the gastrointestinal tract, but they cause irritation of the gastric mucosa
Solution Approach 1:
The enteric coating layer serves as a protective intermediary that shields the gastric mucosa from direct contact with gastric mucosa-aggressive compounds. This layer allows the compound to be delivered to the intestine while preventing harmful interactions with the stomach lining, thus resolving the contradiction between oral administration and mucosal irritation.
3Duration of action of moving object
If controlled-release formulations are used, then the duration of action is extended, but the compounds must remain stable in liquid formulations for extended periods
Solution Approach 1:
The outer enteric coating layer is designed to be temporarily protective during storage and transit, but to dissolve or degrade in the intestinal environment to allow controlled release. This short-lived protective layer enables extended duration of action while maintaining formulation stability during storage, resolving the contradiction between release duration and composition stability.
4Reliability
If multilayered microparticles are designed with protective coating, then compound stability is improved, but the device complexity increases
Solution Approach 1:
The coating layers are designed with specific parameter characteristics: the enteric coating layer has specific pH responsiveness and degradation properties that allow it to provide protection under certain conditions (acidic environment during storage) and release under other conditions (intestinal environment). By optimizing these parameters, the patent achieves compound stability without excessive structural complexity.
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 microparticles maintain pharmaceutical efficacy for several hours to weeks, providing controlled release in the intestines without degrading in acidic conditions, suitable for patients with swallowing impairments.
Implementation Method 1
an outmost external protection coating layer surrounding the controlled-release intermediate coating layer and containing a mixture of a) a hydrophilic gastro-soluble component which is insoluble in aqueous media at a pH of between 6.5 and 7.5
Implementation Method 2
b) a hydrophobic and/or insoluble component
Data Source
AI summary
A controlled-release multilayer microparticle containing a pharmaceutically active compound, which is intended for oral administration or direct administration in the stomach, which may be done using a liquid pharmaceutical composition containing the microparticle. The microparticle may include: a core that includes the pharmaceutically active compound, which may be pramipexole; a controlled-release intermediate coating layer; and an outmost external protection coating layer surrounding the controlled-release intermediate coating layer. The external protection coating layer may include a mixture of: a hydrophilic gastro-soluble component which is insoluble in aqueous media at a pH of between 6.5 and 7.5; and a hydrophobic and/or insoluble component. Also disclosed are a liquid pharmaceutical composition containing the microparticles, a kit for the preparation of the liquid pharmaceutical composition, a pharmaceutical solid composition reconstitutable as the liquid composition, a process of preparing the liquid composition, and a method for treating disease with the liquid composition.