pH-Responsive Copolymer Coating for Drug Form Mechanical Stability

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Solution Overview

Problem

Existing drug forms with copolymers for intestinal juice solubility face challenges in mechanical stability and release profiles, particularly at high pH values, and are unsuitable for multiparticulate drug forms due to poor resistance to mechanical loads and inappropriate dissolution profiles.

Innovation Solution

A copolymer composed of 20-33% methacrylic acid, 5-30% methyl acrylate, 20-40% ethyl acrylate, and more than 10-30% butyl methacrylate, with a glass transition temperature of 55-70°C, is used to create a mechanically stable and pH-specific release profile for drug forms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If copolymers are used to form thin coatings for controlled release, then release characteristics are improved, but mechanical stability deteriorates

Engineering Contradiction:
Improvecoating thickness controlVSAvoidmechanical stability
Core Design Contradiction:
Manufacturing precisionVSStrength

Solution Approach 1:

The patent changes the chemical composition parameters of the copolymer by incorporating specific ratios of methacrylic acid (20-33%), methyl acrylate (5-30%), ethyl acrylate (20-40%), and butyl methacrylate (10-30%), which fundamentally alters the mechanical properties and enables thin coating stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite copolymer system combining multiple monomer components with different properties - methacrylic acid for pH responsiveness, methyl acrylate for flexibility, ethyl acrylate for mechanical strength, and butyl methacrylate for film stability - achieving both thin coating viability and mechanical integrity

Inventive Principle:
Principle #40Composite materials

2Manufacturing precision

If copolymers are used for multiparticulate drug forms under high compression, then dosage uniformity is improved, but coating reliability deteriorates

Engineering Contradiction:
Improvedosage uniformityVSAvoidcoating reliability
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent modifies the copolymer's mechanical parameters through specific monomer selection and ratios, creating a coating that maintains its integrity under high compression forces during multiparticulate form production while ensuring uniform dosage

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If copolymers are used for high pH release profiles, then release characteristics are improved, but mechanical resistance deteriorates

Engineering Contradiction:
Improverelease profile controlVSAvoidmechanical resistance
Core Design Contradiction:
Manufacturing precisionVSStrength

Solution Approach 1:

The patent adjusts the copolymer composition parameters to balance pH-dependent release characteristics with mechanical resistance, using specific proportions of acid-containing monomers for release control and other monomers for structural integrity at high pH levels

Inventive Principle:
Principle #35Parameter changes

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 copolymer provides a mechanically stable film with controlled release characteristics suitable for intestinal absorption, ensuring reliable mechanical stability and targeted release of active ingredients in the upper intestine.

Implementation Method 1

the glass transition temperature of the copolymer in accordance with ISO 11357-2, section 3.3.3, is 55 to 70° C.

Methodology Applied
Scientific EffectGlass transition temperature:

Implementation Method 2

which form comparatively flexible films and have release profiles that are suitable for many drugs

Methodology Applied
Scientific EffectPolymer film formation:

Implementation Method 3

which dissolve only above a pH of 6.5, and hence in relatively low sections of the intestine

Methodology Applied
Scientific EffectpH-dependent dissolution:

Implementation Method 4

copolymers of 10 to 25% by weight methacrylic acid, 40 to 70% by weight methyl acrylate and 20 to 40% by weight methyl methacrylate

Methodology Applied
Scientific EffectIonization: Ionisation

Data Source

PatentUS7498044B2Dosage form and method for producing the same
Publication Date: 2009.03.03 EVONIK OPERATIONS GMBH

AI summary

The invention relates to a process for producing a coated drug form or a drug form in the form of an active ingredient matrix, by processing a copolymer, an active pharmaceutical ingredient, a core if present and/or pharmaceutically customary excipients in a conventional manner by melting, injection molding, extrusion, wet granulation, casting, dipping, spreading, spraying or compression to form a coated drug form and/or to form an active ingredient matrix, characterized in that a copolymer is used which is composed of 20 to 33% by weight methacrylic acid, 5 to 30% by weight methyl acrylate, 20 to 40% by weight ethyl acrylate and more than 10 to 30% by weight butyl methacrylate and, if desired, 0 to 10% by weight further vinylically copolymerizable monomers, with the proviso that the glass transition temperature of the copolymer in accordance with ISO 11357-2, section 3.3.3, is 55 to 70° C. The invention further relates to the drug form produced in accordance with the invention, to the copolymer, and to the use thereof.