Multiparticulate Vitamin Delivery via pH-Sensitive Coatings

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Solution Overview

Problem

Current delivery systems for water-soluble vitamins, such as tablets and capsules, face limitations in payload capacity, swallowing difficulties for young and elderly patients, variable residence time in the stomach, and premature release due to pH-sensitive coatings, leading to high local concentrations and reduced efficacy for gut and metabolic health.

Innovation Solution

A multiparticulate delivery system comprising a solid core of water-soluble vitamins coated with a crosslinked fermentable biopolymer inner layer and a stomach-resistant outer layer, allowing controlled release in the small intestine, with the option to incorporate additional nutraceuticals and production via batch or continuous processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If water-soluble vitamins are formulated as powdery particles or granules with readily dissolved matrix materials, then the vitamins are easily released and absorbed, but they are released in the stomach or small intestine and do not reach the large intestine

Engineering Contradiction:
Improveease of releaseVSAvoidtargeted delivery to large intestine
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The delivery system is segmented into multiple particles (pellets, beads, or granules) rather than a single tablet or capsule. This multiparticulate approach allows for better distribution and controlled release characteristics while maintaining the ability to target specific intestinal regions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the release parameter by using pH-sensitive coatings that respond to the pH gradient along the GI tract. The coating materials (cellulose acetate phthalate, poly vinyl acetate phthalate, hydroxypropyl methyl cellulose phthalate, or methacrylic acid copolymers) are selected to dissolve at specific pH levels, ensuring release occurs in the large intestine rather than the stomach or small intestine.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If controlled release capsules or tablets are used with pH-sensitive coatings, then release in the small or large intestine is achieved, but the amount of active substance is limited by available volume and residence time in the stomach is very variable

Engineering Contradiction:
Improvecontrolled release locationVSAvoidpayload capacity
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

By segmenting the delivery system into multiple small particles rather than a single large tablet or capsule, the total surface area increases while maintaining a compact form factor. This allows for greater payload capacity within the same volume constraint and improves mixing and distribution in the GI tract.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses thin film coatings on each particle that provide pH-sensitive release functionality without adding significant volume. This allows maximum payload capacity within the available volume while maintaining the controlled release capability.

Inventive Principle:
Principle #30Flexible shells and thin films

3Reliability

If controlled release coatings are applied to multiparticulate dosage forms, then release control is improved, but the larger specific surface area requires much higher amounts of coating material, reducing available space for payload

Engineering Contradiction:
Improvecontrolled release performanceVSAvoidpayload capacity
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The invention employs thin film coatings rather than thick layers, which provides sufficient pH-sensitive release control while minimizing the volume occupied by the coating material. This maximizes the payload capacity within each particle.

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The selection of specific pH-sensitive polymer materials allows for optimized coating thickness and composition. By choosing polymers with appropriate molecular weights and compositions, the coating provides effective release control with minimal material requirements.

Inventive Principle:
Principle #35Parameter changes

4Ease of manufacture

If pH-sensitive coating materials are used for controlled release, then release in the small intestine is achieved, but premature drug release may occur in the small intestine due to variation in GI motility

Engineering Contradiction:
Improverelease mechanismVSAvoidrelease timing precision
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The invention uses composite coating systems combining multiple pH-sensitive polymers or combining pH-sensitive polymers with other functional materials. This creates a more robust release mechanism that is less sensitive to variations in GI motility and pH fluctuations, ensuring more precise release timing in the large intestine.

Inventive Principle:
Principle #40Composite materials

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

Enhances the stability and efficacy of water-soluble vitamins by ensuring targeted release in the large intestine, improving payload capacity and industrial scalability while avoiding premature release and high local concentrations.

Implementation Method 1

The colonic bacteria are predominately anaerobic in nature and secrete enzymes that are capable of metabolizing both endogenous and exogenous substrates such as carbohydrates and proteins that escape digestion in the upper GI tract

Methodology Applied
Scientific EffectFermentation: Fermentation

Implementation Method 2

Polysaccharides naturally occurring in plant (e.g., pectin, guar gum, inulin), animal (e.g., chitosan, chondroitin sulfate), algal (e.g., alginates), or microbial (e.g., dextran) origins were studied for colon targeting. These are broken down by the colonic microflora to simple saccharides by saccharolytic species like bacteroides and bifidobacteria

Methodology Applied
Scientific EffectEnzyme degradation: Enzyme

Implementation Method 3

The use of GI microflora as a mechanism of drug release in the colonic region has been of great interest to researchers in the past. The majority of bacteria are present in the distal gut although they are distributed throughout the GI tract

Methodology Applied
Scientific EffectpH-sensitive dissolution:

Data Source

PatentUS20220193033A1New delivery system for specific water-soluble vitamins
Publication Date: 2022.06.23 DSM IP ASSETS BV

AI summary

The present invention relates to a new delivery system for specific water-soluble vitamins.