Mesalamine Pellet Coating Process in Fluid Bed

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Solution Overview

Problem

The existing processes for manufacturing mesalamine pellets are inefficient, requiring multiple machines and steps, leading to a slower, less reproducible, and aesthetically unappealing product with low drug content suspension.

Innovation Solution

A process that integrates all steps, including drug layering, seal coating, extended release coating, and color coating, into a single automated fluid bed coater, using specific ingredients like hypromellose, polysorbate 80, ethyl cellulose, and dibutyl sebacate, to produce spherical pellets with improved appearance and release control.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional multi-machine manufacturing process is used, then manufacturing flexibility is maintained, but process speed and productivity are reduced

Engineering Contradiction:
Improveprocess speedVSAvoidnumber of machines
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent combines multiple coating operations (drug layering, seal coating, extended release coating, color coating) that were previously performed on separate machines into a single fluid bed coater. This consolidation integrates multiple manufacturing functions into one device, increasing process speed and productivity while maintaining the necessary manufacturing flexibility through programmable control of each coating step.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The fluid bed coater is designed to perform multiple coating functions sequentially within a single machine. The device can switch between different coating modes (drug layering, seal coating, extended release coating, color coating) by changing parameters and coatings, making it a universal machine that replaces several specialized machines while maintaining operational versatility.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Manufacturing precision

If conventional layering process is used, then manufacturing simplicity is maintained, but drug content suspension quality and aesthetic appearance are compromised

Engineering Contradiction:
Improvedrug content suspension qualityVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent prepares optimized drug content suspensions in advance with precise formulation (including surfactants and binders) before the coating process. This preliminary preparation ensures high-quality drug content suspension that adheres properly to pellets, improving manufacturing precision while the automated fluid bed coater handles the complex layering operations efficiently.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses composite coating formulations including multiple components (mesalamine, surfactants like polysorbate 80, binders like hypromellose, release-controlling agents like ethyl cellulose) to create multi-functional coatings. These composite materials provide both therapeutic functionality and aesthetic appearance while the automated process maintains ease of manufacture.

Inventive Principle:
Principle #40Composite materials

3Reliability

If multiple coating steps are performed on separate machines, then process control is simplified, but manufacturing time and reproducibility are adversely affected

Engineering Contradiction:
ImprovereproducibilityVSAvoidmanufacturing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent implements continuous coating operations within a single fluid bed coater, where pellets undergo sequential coating steps (drug layering, seal coating, extended release coating, color coating) without removal or interruption. This continuous process eliminates transfer time between machines and ensures consistent pellet treatment, improving reproducibility while reducing total manufacturing time through automated sequential operations.

Inventive Principle:
Principle #20Continuity of useful action

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

This approach results in a faster, more robust, and reproducible process for mesalamine pellets with enhanced appearance and therapeutic efficacy, offering better patient compliance and reduced dosing frequency.

Implementation Method 1

performing a first drug layering in the fluid bed coater by applying the first drug layering suspension on sugar spheres to form first drug layered pellets

Methodology Applied
Scientific EffectFluidization: Fluidisation

Implementation Method 2

about 17 to about 19 percent by weight of a binder wherein the binder is hypromellose; about 4 to about 5 percent by weight of a release controlling agent wherein the release controlling agent is ethyl cellulose

Methodology Applied
Scientific EffectMatrix formation:

Implementation Method 3

about 0.50 to about 0.80 percent by weight of a surfactant wherein the surfactant is polysorbate 80

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Implementation Method 4

about 2 to about 3 percent by weight of a pore forming agent wherein the pore forming agent is polyvinyl pyrrolidone

Methodology Applied
Scientific EffectPore formation: Porosity

Data Source

PatentEP3131535B1Process for preparation of mesalamine composition and mesalamine composition thereof
Publication Date: 2020.04.29 ATHENA PHARMACEUTIQUES SAS
  • EP3131535B1 patent drawingFigure 1
  • EP3131535B1 patent drawingFigure 2
  • EP3131535B1 patent drawingFigure 3

AI summary

A process for preparation of a mesalamine composition, comprising: preparing a first drug layering suspension comprising mesalamine; performing a first drug layering in the fluid bed coater to form first drug layered pellets; preparing a seal coating suspension; performing the seal coating in the fluid bed coater on the first drug layered pellets to form seal coated pellets; preparing a second drug layering suspension comprising mesalamine; performing the second drug layering in the fluid bed coater on seal coated pellets to form second drug layered pellets; preparing an extended release coating suspension; performing the extended release coating in the fluid bed coater on the second drug layered pellets to form extended release pellets; preparing a color coating suspension; performing the color coating in the fluid bed coater on the extended release pellets to form color coated pellets; and lubricating the color coated pellets to form mesalamine pellets.