Matrix Mesalamine Minitablets Without Coating

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Solution Overview

Problem

Current methods for producing controlled release mesalamine formulations are complex, expensive, and involve multiple steps, including spheronization, layering, and polymeric coating, which are time-consuming and require organic solvents, making it challenging to achieve high drug load and controlled release in matrix minitablets without these processes.

Innovation Solution

A pharmaceutical composition comprising mesalamine with a high drug load of 70-85% weight percentage, combined with controlled release excipients, binders, and diluents, glidants, and lubricants, which are processed using wet or dry granulation or direct compression to create matrix minitablets without spheronization, layering, or polymeric coating, allowing for controlled release similar to marketed products like PENTASA.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods (spheronization, layering, polymeric coating) are used to produce controlled release mesalamine formulations, then controlled release profile is achieved, but manufacturing complexity and cost increase significantly

Engineering Contradiction:
Improvecontrolled release profileVSAvoidmanufacturing process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the complex coating and layering steps from the manufacturing process. Instead of using conventional multi-step processes involving spheronization, seed layering, and polymeric coating, the invention uses a simplified direct compression or granulation process that achieves controlled release through the matrix formulation itself, removing the need for separate controlled release coating operations.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent combines the drug substance, controlled release excipients, and binding agents into a single integrated matrix formulation. The controlled release functionality is merged directly into the tablet matrix through the selection of specific excipients (such as hydrophilic polymers, lipids, or biodegradable materials) that provide sustained release without requiring separate coating layers.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If multiple coating and layering steps are used, then controlled release is achieved, but production time and cost increase

Engineering Contradiction:
Improvecontrolled releaseVSAvoidproduction efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent incorporates controlled release excipients and binding agents directly into the formulation mix before compression or granulation. This preliminary incorporation of release-controlling materials eliminates the need for subsequent coating operations, allowing the controlled release functionality to be built into the tablet structure during the primary manufacturing step.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention skips the intermediate coating and layering steps that are conventional in controlled release formulation. By using a direct compression or single-step granulation approach with pre-mixed controlled release excipients, the process rushes through to final tablet formation without the time-consuming sequential operations of spheronization, seed coating, and multiple layer applications.

Inventive Principle:
Principle #21Skipping (Rushing through)

3Quantity of substance

If high drug load (70-85% w/w) is achieved in matrix minitablets, then dosage efficiency improves, but manufacturing precision requirements increase

Engineering Contradiction:
Improvedrug loadVSAvoidformulation uniformity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent achieves high drug load by carefully selecting and optimizing the parameters of the matrix-forming excipients. By choosing excipients with appropriate particle size, density, and binding characteristics, and by optimizing the compression force and granulation parameters, the formulation achieves 70-85% drug load while maintaining uniform distribution and consistent manufacturing quality.

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 solution enables the production of mesalamine matrix minitablets with a controlled release profile, high drug load, and simplified manufacturing, achieving similar dissolution profiles to existing products across various pH levels, while eliminating the need for complex coating processes and organic solvents, thus reducing costs and processing time.

Implementation Method 1

The controlled release of mesalamine from the matrix minitablets occurs through diffusion of the drug molecules through the excipient matrix

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

The matrix structure undergoes erosion as the excipient degrades, releasing mesalamine in a controlled manner

Methodology Applied
Scientific EffectErosion:

Implementation Method 3

The binder adheres the mesalamine particles and excipients together to form a cohesive matrix structure

Methodology Applied
Scientific EffectAdhesion: Adhesive

Implementation Method 4

The liquid binder moves through the powder mixture via capillary action, binding particles together

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 5

Surface tension of the liquid binder facilitates particle aggregation during wet granulation

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Implementation Method 6

The granulated mixture is compressed under high pressure to form dense, solid minitablets with controlled porosity

Methodology Applied
Scientific EffectCompression: Compression

Data Source

PatentUS11975011B2Matrix mesalamine extended release minitablets and its process thereof
Publication Date: 2024.05.07 ATOZ PHARMA PVT LTD

AI summary

Compositions for development of matrix type extended release mesalamine minitablets without use of any modified release coating, comprising a) mesalamine or its prodrug or derivatives thereof having a weight percentage in a range of 65-85 weight percentage with respect to the composition; b) at least one intragranular excipient having a weight percentage in a range of 3.5-22.5 weight percentage with respect to the composition; c) at least one binder having a weight percentage in a range of 2-6.5 weight percent with respect to the composition; and d) at least one extra granular excipient having a weight percentage in a range of 2-5 weight percentage with respect to the composition such that largest dimension in the minitablet is range of 1.00 mm to 2.8 mm. In another aspect of the present disclosure provides for a process of preparation of composition.