Gastro-resistant Microspheres for Intestinal Drug Release

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Solution Overview

Problem

Current pharmaceutical compositions for the oral administration of beclomethasone dipropionate do not ensure homogeneous and complete release of the active ingredient at the targeted intestinal site, leading to inadequate pharmacological response and distribution in treating chronic inflammatory intestinal diseases.

Innovation Solution

The development of modified-release gastro-resistant microspheres, comprising an inert core coated with beclomethasone dipropionate and a modified-release gastro-resistant coating, allows for a more site-specific and homogeneous release of the active ingredient at the intestinal mucosa, specifically in the ileum and colon, enhancing contact surface and pharmacological action.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional slow-release tablets are used for oral administration of beclomethasone dipropionate, then the drug can be administered orally, but the release of active ingredient is not homogeneous and not complete at the targeted intestinal site

Engineering Contradiction:
Improvehomogeneity of active ingredient releaseVSAvoidcompleteness of active ingredient release
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The invention divides the pharmaceutical composition into multiple microspheres with different release characteristics. Each microsphere contains beclomethasone dipropionate embedded in a polymer matrix, and the segmentation of the drug delivery system into numerous small units ensures more uniform distribution and release compared to a single large tablet form.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention creates microspheres with specific local properties - the active ingredient is embedded within the polymer matrix of each microsphere, creating a localized reservoir that releases drug in a controlled manner. The gastro-resistant coating is applied specifically to protect the drug through the gastric environment while allowing release in the intestinal environment, providing location-specific drug release characteristics.

Inventive Principle:
Principle #3Local quality

2Reliability

If cortisones are administered systemically, then high anti-inflammatory activity is achieved, but important adverse effects occur due to action on the hypophysis-cortico-adrenal system

Engineering Contradiction:
Improveanti-inflammatory activityVSAvoidadverse effects on hypophysis-cortico-adrenal system
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The invention extracts the harmful systemic effects by creating a delivery system that targets the drug specifically to the intestinal tract. The gastro-resistant microspheres release beclomethasone dipropionate locally in the intestine, separating the therapeutic anti-inflammatory action at the target site from the harmful systemic effects that occur with conventional oral tablet administration.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The gastro-resistant microsphere acts as an intermediary vehicle that carries beclomethasone dipropionate through the gastric environment and releases it specifically in the intestinal tract. This intermediary system enables the drug to reach its target site without being absorbed systemically in the stomach, thereby maintaining anti-inflammatory efficacy while avoiding adverse effects on the hypophysis-cortico-adrenal system.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-generated harmful factors

If cortisones are administered rectally, then fewer side effects occur, but the proximal tracts of the colon cannot be reached

Engineering Contradiction:
Improveside effectsVSAvoidreachability of proximal colon tracts
Core Design Contradiction:
Object-generated harmful factorsVSLength of moving object

Solution Approach 1:

Instead of administering the drug rectally (from the end of the colon), the invention inverts the approach by using oral administration with gastro-resistant microspheres that travel through the entire gastrointestinal tract and release the drug along the intestinal path, including the proximal colon tracts that are inaccessible to rectal administration.

Inventive Principle:
Principle #13The other way round (Inversion)

4Ease of operation

If beclomethasone dipropionate is delivered in slow-release tablets, then oral administration is possible, but the distribution and homogeneity of content of the active ingredient is insufficient

Engineering Contradiction:
Improveoral administration capabilityVSAvoiddistribution homogeneity of active ingredient
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The invention segments the drug delivery system into numerous microspheres that can be easily administered orally (maintaining ease of operation) while the segmented structure ensures better distribution and homogeneity of the active ingredient throughout the gastrointestinal tract compared to a single large tablet.

Inventive Principle:
Principle #1Segmentation

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 modified-release gastro-resistant microspheres achieve a release of over 70% of the active ingredient on the intestinal mucosa, particularly in the distal ileum and colon, amplifying the anti-inflammatory effect and ensuring better distribution and homogeneity, thus improving the treatment of inflammatory intestinal pathologies.

Implementation Method 1

The microsphere is coated with a modified-release gastro-resistant film... capable of carrying and releasing at the level of the intestinal mucosa... release of pharmacologically active agents at the level of the colon or rectum

Methodology Applied
Scientific EffectpH-dependent solubility:

Implementation Method 2

The microspheres are coated with a modified-release gastro-resistant film... polymers and/or copolymers of acrylic acid and/or of methacrylic acid

Methodology Applied
Scientific EffectpH-dependent dissolution:

Data Source

PatentEP3009130B1Beclomethasone dipropionate compositions in modified-release gastro-resistant microspheres
Publication Date: 2018.10.10 SOFAR SPA
  • EP3009130B1 patent drawingFigure 1

AI summary

The present invention refers to pharmaceutical beclomethasone dipropionate compositions in modified-release gastro-resistant microspheres and to their oral use in the treatment of inflammatory pathologies of the intestinal tract. Said compositions in microspheres consist of: a) a core consisting of a microsphere of inert material; b) a first intermediate coating comprising beclomethasone dipropionate and at least one physiologically acceptable excipient; c) a second modified-release gastro-resistant coating. The present disclosure also refers to a process for obtaining said compositions.