Ethanol-Resistant pH-Controlled Drug Release Coating

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Solution Overview

Problem

Current pharmaceutical formulations for non-opioid drugs are susceptible to ethanol, leading to unintended acceleration or slowing of drug release, which can be harmful, especially when consumed with alcoholic beverages, and existing technologies do not adequately address this issue.

Innovation Solution

A pH-dependent controlled release pharmaceutical composition is developed, featuring a core coated with a polymer mixture containing a water-insoluble neutral vinyl polymer and an anionic polymer, along with a non-porous inert lubricant like talc, to maintain consistent drug release profiles even in the presence of ethanol.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional pharmaceutical formulations are used, then drug release can be controlled under normal conditions, but the formulation becomes susceptible to ethanol influence leading to unintended acceleration or slowing of drug release

Engineering Contradiction:
Improvedrug release controlVSAvoidethanol susceptibility
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs a composite coating system consisting of multiple polymer layers with distinct functions. The outer layer uses ethanol-resistant polymers (acrylic or methacrylate copolymers) to block ethanol penetration, while inner layers provide pH-dependent drug release control. This multi-layer composite structure resolves the contradiction by combining ethanol resistance with controlled release functionality.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

Different regions of the coating have specialized properties: the outermost layer is specifically designed for ethanol resistance, while inner layers are optimized for pH-responsive drug release. The coating thickness and composition vary locally to achieve both protection against ethanol and controlled drug release under physiological conditions.

Inventive Principle:
Principle #3Local quality

2Reliability

If a thick coating layer is applied to increase ethanol resistance, then drug release becomes resistant to ethanol, but the manufacturing complexity and coating material requirements increase

Engineering Contradiction:
Improveethanol resistanceVSAvoidcoating structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The coating is divided into multiple thin layers rather than one thick layer. Each layer has a specific thickness optimized for its function, making the overall structure more manageable and manufacturable. The segmented approach allows better control over drug release kinetics while achieving ethanol resistance through the outermost layer.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent optimizes coating parameters such as polymer composition ratios, layer thicknesses, and crosslinking degrees to achieve ethanol resistance with minimal coating mass. By adjusting these parameters, the formulation achieves protection against ethanol without excessive coating complexity.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If pH-dependent release is implemented, then controlled release under normal conditions is achieved, but the release profile becomes sensitive to pH changes including those caused by ethanol consumption

Engineering Contradiction:
Improvecontrolled release efficiencyVSAvoidpH sensitivity
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The outer polymer layer acts as an intermediary barrier that prevents ethanol from reaching the pH-sensitive inner layers. This mediator layer allows the pH-dependent release mechanism to function normally under physiological conditions while blocking the harmful effect of ethanol-induced pH changes in the gastric environment.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The pH-sensitive polymer components are localized in inner coating layers away from the external environment, while the outer layer provides a stable, ethanol-resistant barrier. This spatial separation allows pH-dependent release control without sensitivity to external pH fluctuations caused by ethanol consumption.

Inventive Principle:
Principle #3Local quality

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 composition ensures that the drug release is resistant to ethanol, maintaining a consistent release profile with less than 20% variation in the presence of 40% ethanol, thereby reducing the risk of adverse effects from ethanol consumption.

Implementation Method 1

the polymer mixture comprises i) 40-95, preferably 50-80 % by weight, based on dry weight of the polymer mixture, of at least one water insoluble essentially neutral vinyl polymer or copolymer, which polymer contains less than 5% by weight of monomer residues with anionic or cationic side groups and ii) 5-60, preferably 20-50 % by weight, based on dry weight of the polymer mixture, of at least one anionic polymer or copolymer, which is insoluble in a buffered medium below pH 4.0 and soluble at least in the range from pH 7.0 to pH 8.0

Methodology Applied
Scientific EffectpH-dependent solubility:

Implementation Method 2

the coating layer further contains 110 to 250, preferably 140 - 220 % by weight, calculated on dry weight of the polymer mixture, of a non-porous inert lubricant

Methodology Applied
Scientific EffectLubrication: Lubrication

Data Source

PatentEP2187875B1Ph-dependent controlled release pharmaceutical composition for non-opioids with resistance against the influence of ethanol
Publication Date: 2012.09.05 ROHM GMBH

AI summary

The invention relates to a pH-dependent controlled release pharmaceutical composition, comprising at least one pharmaceutical active ingredient, with the exception of opioids, wherein the core is coated at least by one coating layer, controlling the release of the pharmaceutical composition, wherein the coating layer comprises a polymer mixture of i) 40 - 95 % by weight, based on dry weight of the polymer mixture, of at least one water insoluble essentially neutral vinyl polymer or copolymer, and ii) 5 - 60 % by weight, based on dry weight of the polymer mixture, of at least one anionic polymer or copolymer, which is insoluble in a buffered medium below pH 4.0 and soluble at least in the range from pH 7.0 to pH 8.0. characterized in that the coating layer further contains 110 to 250 % by weight, calculated on dry weight of the polymer mixture, of a non-porous inert lubricant and the is present in an amount of at least 60 % by weight calculated on the weight of core.