Vacuum-Dried Probiotic Microcapsules for Gastric Stability

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Solution Overview

Problem

Existing methods for delivering probiotic bacteria via the oral route face challenges in maintaining the viability of heat-sensitive active agents due to high heat processes, leading to thermal damage and instability under gastric conditions.

Innovation Solution

The development of microcapsules with a protein matrix, specifically using denatured whey protein, which are cold-gelated and vacuum dried in two stages to create low water activity microcapsules that are resistant to gastric conditions, allowing for gradual release in the ileum and enhanced stability against moisture and heat.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high heat processes are used to produce microcapsules, then the microcapsules achieve good structural stability and encapsulation efficiency, but the probiotic bacteria suffer thermal damage and loss of viability

Engineering Contradiction:
Improvemicrocapsule structural stabilityVSAvoidthermal damage to probiotics
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the temperature parameter from conventional high heat processes to cold gelation (room temperature or refrigeration temperatures). The protein matrix is gelated at low temperatures, eliminating thermal damage to probiotics while still achieving proper microcapsule structure and stability through alternative mechanisms such as protein denaturation and cross-linking at low temperatures.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces thermal processing mechanisms with mechanical and chemical mechanisms. Instead of using heat to set the microcapsule structure, the invention uses cold gelation involving protein denaturation, cross-linking, and extrusion forces to form the microcapsule matrix, thereby avoiding thermal damage to heat-sensitive probiotics.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If conventional drying methods are used to produce microcapsules, then the microcapsules achieve adequate moisture removal, but the probiotics lose stability and viability due to high temperature exposure

Engineering Contradiction:
Improvemoisture content reductionVSAvoidthermal damage to probiotics
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent changes the drying temperature parameter from conventional high temperature drying to vacuum drying at low or room temperatures. This parameter change allows effective moisture removal while maintaining probiotic stability and viability, as the vacuum drying process removes water at temperatures that do not damage the probiotic bacteria.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses vacuum conditions as an inert environment for drying. The vacuum atmosphere allows moisture removal without exposure to ambient air and high temperatures, creating a protective environment that preserves probiotic viability while achieving the desired moisture content reduction.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

3Duration of action of moving object

If the microcapsule matrix is designed to break up quickly in the stomach, then rapid release of probiotics is achieved, but the probiotics are exposed to harsh gastric conditions before release

Engineering Contradiction:
Improverelease speedVSAvoidexposure to gastric conditions
Core Design Contradiction:
Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary protective action by coating the probiotics with a protective protein matrix before they encounter harsh gastric conditions. The microcapsule matrix is designed to resist gastric acid and enzymes initially, protecting the probiotics during transit through the stomach, and then breaks down in the ileum to release the protected probiotics.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces the protein matrix as an intermediary protective layer between the probiotics and harsh gastric conditions. This intermediary matrix absorbs the harmful effects of gastric acid and enzymes, protecting the probiotics until they reach the ileum where the matrix breaks down to release the protected bacteria.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Ease of operation

If the microcapsules are designed with high water activity for ease of handling, then the microcapsules are easier to process, but the microcapsules show reduced stability against moisture and humidity

Engineering Contradiction:
Improvehandling easeVSAvoidstability against moisture and humidity
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent changes the water activity parameter to achieve the desired stability. By controlling the drying process to achieve low water activity (0.25 or less), the microcapsules gain enhanced stability against moisture and humidity while maintaining adequate handling properties through proper formulation and packaging.

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

This approach effectively protects and stabilizes probiotic bacteria, ensuring a prolonged release profile and maintaining a high payload of active probiotics, with a high encapsulation efficiency and ability to survive in gastric conditions, thus addressing the challenges of thermal damage and instability.

Implementation Method 1

the matrix comprises or consists essentially of denatured protein

Methodology Applied
Scientific EffectProtein denaturation:

Implementation Method 2

cold gelation (e.g. extrusion into a curing/gelation) bath

Methodology Applied
Scientific EffectGelation: Gel

Implementation Method 3

drying by vacuum drying

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 4

vacuum drying in two separate vacuum drying steps

Methodology Applied
Scientific EffectVacuum: Vacuum

Implementation Method 5

configured to break up in the ileum, releasing the contents gradually over a period of time

Methodology Applied
Scientific EffectEnzymatic digestion: Enzyme

Data Source

PatentUS20230321161A1A compositon comprising microcapsules
Publication Date: 2023.10.12 TEAGASC THE AGRI & FOOD DEVMENT AUTHORITY

AI summary

A composition comprising microcapsules in an oral dosage form is described. The oral dosage form comprises gastric-resistant ileal-sensitive microcapsules comprising a matrix and active agent such as probiotic bacterium, contained within the matrix, in which the matrix comprises denatured whey protein, and in which the microcapsules are be coldgelated and vacuum dried microcapsules, and thus are subject to less heat treatment than conventional probiotic-containing microparticles. The microcapsules may be formed by extrusion through a single or double nozzle and are vacuum dried to a water activity (Aw) of 0.30 or less. The microcapsules may be subjected to two separate vacuum drying steps to further reduce the water activity and provide microcapsules with greater stability against moisture, humidity and thermal processes such as pasteurisation and Ultra High Temperatures (i.e. UHT)