Enteric Coated MGBG Dosage Form for Oral Bioavailability

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Solution Overview

Problem

MGBG, a potent cancer chemoprevention agent, faces challenges due to severe toxicity and limited bioavailability, particularly when administered intravenously, which is inconvenient, costly, and risky, especially for immunocompromised individuals, and oral formulations are hindered by gastrointestinal side effects and dose-limiting toxicity.

Innovation Solution

Development of controlled-release oral pharmaceutical dosage forms of MGBG, including delayed-release tablets or capsules with enteric coatings that dissolve in the duodenum, reducing gastrointestinal side effects and enhancing bioavailability, allowing for chronic low-dose administration and combination with other therapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If MGBG is administered intravenously, then bioavailability is achieved, but convenience is reduced and infection risk increases

Engineering Contradiction:
ImprovebioavailabilityVSAvoidconvenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent uses an enteric coating as an intermediary layer between the MGBG drug and the gastric environment. This coating allows the drug to survive stomach conditions and be released in the intestine, achieving oral bioavailability while maintaining patient convenience and avoiding IV-related infection risks

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If MGBG is administered orally, then convenience is improved, but gastrointestinal toxicity increases

Engineering Contradiction:
ImproveconvenienceVSAvoidgastrointestinal toxicity
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The enteric coating acts as a protective intermediary that prevents direct contact between MGBG and the gastric mucosa. The coating remains intact in the acidic stomach environment and only dissolves in the more neutral pH of the intestine, thereby eliminating GI toxicity while preserving oral administration convenience

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The enteric coating is applied in advance to the MGBG dosage form before administration. This preliminary protective action ensures that the drug is shielded from gastric damage before it can cause toxicity, allowing safe oral delivery

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If MGBG is administered orally without controlled release, then ease of use is improved, but bioavailability is reduced due to gastric destruction

Engineering Contradiction:
Improveease of useVSAvoidbioavailability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The enteric coating serves as a protective intermediary that enables the orally administered MGBG to withstand gastric conditions. This simple oral dosage form with coating achieves both ease of use and reliable bioavailability by preventing gastric destruction of the drug

Inventive Principle:
Principle #24Intermediary (Mediator)

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 controlled-release formulation significantly reduces gastrointestinal side effects by at least 30% and maintains therapeutic efficacy with improved bioavailability, enabling safer and more convenient chronic administration of MGBG, particularly for immunocompromised patients.

Implementation Method 1

delayed-release tablets or capsules with enteric coatings that dissolve in the duodenum

Methodology Applied
Scientific EffectDissolution:

Data Source

PatentEP2665471B1Controlled release oral pharmaceutical dosage forms comprising mgbg
Publication Date: 2017.12.27 PATHOLOGICA LLC
  • EP2665471B1 patent drawingFigure 1
  • EP2665471B1 patent drawingFigure 2
  • EP2665471B1 patent drawingFigure 3

AI summary

Disclosed herein are controlled-release oral pharmaceutical dosage forms comprising MGBG, and their application for the improved treatment of diseases with reduced side effects and/or longer time at maximum concentration.