Polymeric Fill Matrix for Softgel Capsule Stability

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Solution Overview

Problem

Traditional softgel capsule formulations face issues such as degradation of active ingredients due to water migration from the shell, interactions between fill and shell components, and require extensive drying processes, which are time-consuming and resource-intensive. Additionally, existing polymeric fill materials do not disintegrate or dissolve in the gastrointestinal tract, leading to intestinal problems.

Innovation Solution

A softgel formulation using a polymeric fill matrix formed from activated monomers without water, which minimizes interactions between fill and shell components, reduces water migration, and is sensitive to pH, allowing for immediate or delayed release of active ingredients. This matrix is formed through polymerization of monomers, solvents, and photoinitiators, eliminating the need for cross-linking agents and reducing drying time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a traditional softgel shell containing water is used, then the shell provides good flexibility and digestibility, but water migrates from the shell to the fill causing degradation of hydrolysis-sensitive active ingredients

Engineering Contradiction:
Improveshell flexibility and digestibilityVSAvoidstability of hydrolysis-sensitive active ingredients
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent removes water from the fill formulation by using a non-aqueous polymeric matrix system. The fill contains no water, thereby eliminating the source of water migration that causes hydrolysis of sensitive active ingredients like aspirin, while the gelatin shell retains its water content for flexibility and digestibility.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses a composite polymeric matrix formulation consisting of multiple polymers (such as polyethylene glycol, polyvinyl alcohol, carboxymethyl cellulose) combined with excipients to create a water-free or low-water fill system that maintains structural integrity and drug stability without relying on aqueous solutions.

Inventive Principle:
Principle #40Composite materials

2Ease of manufacture

If a traditional liquid or suspension fill is used, then the formulation is easy to manufacture, but extensive drying processes are required which are time-consuming and resource-intensive

Engineering Contradiction:
Improveformulation simplicityVSAvoiddrying process duration
Core Design Contradiction:
Ease of manufactureVSLoss of time

Solution Approach 1:

The patent changes the fundamental parameter of the fill system from aqueous-based to polymeric matrix-based. This transformation eliminates the need for extensive drying processes because the polymeric matrix inherently binds and retains moisture, allowing the softgel to be filled in a semi-solid or solid state without requiring prolonged drying to achieve low moisture content.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If existing polymeric fill materials are used, then water migration is reduced, but the materials do not disintegrate or dissolve in the gastrointestinal tract causing intestinal problems

Engineering Contradiction:
Improvereduction of water migrationVSAvoidintestinal obstruction risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent creates a dynamic polymeric matrix system that remains stable during storage and manufacturing (preventing water migration) but transforms into a disintegrating structure in the gastrointestinal environment. The polymeric composition is specifically selected to dissolve or break down into safe, excretable components after ingestion, eliminating intestinal obstruction risks.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent applies different properties to the polymeric matrix at different stages: during storage and handling, the matrix maintains structural integrity and low water content; upon contact with gastrointestinal fluids, the matrix becomes soluble and disintegrates. This spatial and temporal differentiation of material properties resolves the contradiction between stability and biodegradability.

Inventive Principle:
Principle #3Local quality

4Reliability

If a polymeric fill matrix formed from activated monomers without water is used, then interactions between fill and shell components are minimized and water migration is reduced, but the formulation complexity increases

Engineering Contradiction:
Improveminimization of fill-shell interactionsVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs polymeric materials that serve multiple functions simultaneously: they provide structural matrix support, bind excipients and active ingredients, prevent water migration, and ensure gastrointestinal solubility. This multi-functionality reduces the need for separate components and simplifies the overall formulation despite the advanced chemistry involved.

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

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 provides stable, fast-release, delayed-release, or sustained-release formulations that prevent intestinal issues, reduce manufacturing time and resources, and ensure the stability of hydrophilic drugs, while allowing for a wide range of excipients and active ingredients, including naproxen, acetylsalicylic acid, and ibuprofen.

Implementation Method 1

The polymeric fill matrix is formed from activated monomers... This matrix is formed through polymerization of monomers, solvents, and photoinitiators

Methodology Applied
Scientific EffectPhotopolymerization: Photopolymerisation

Implementation Method 2

minimizes interactions between fill and shell components, reduces water migration

Methodology Applied
Scientific EffectPermeation: Permeation

Data Source

PatentEP3866758B1Softgels with solid or gel-like polymeric fill matrix
Publication Date: 2024.12.04 BAYER HEALTHCARE LLC
  • EP3866758B1 patent drawingFigure 1~2
  • EP3866758B1 patent drawingFigure 3~4
  • EP3866758B1 patent drawingFigure 5~6

AI summary

Stable dosage forms, preferably of pharmaceutical formulations, that include a solid or semi-solid polymeric mass, which entraps active ingredients and can be formulated for oral administration in a mould, preferably in a softgel capsule.