Metoprolol Oral Liquid Formulation Stability

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Solution Overview

Problem

Current oral liquid formulations of metoprolol tartrate lack stability, palatability, and an acceptable shelf-life, making them unsuitable for elderly and incapacitated patients who require precise dose adjustment and long-term stability.

Innovation Solution

Development of stable oral liquid pharmaceutical formulations comprising metoprolol or its pharmaceutically acceptable salts, combined with preservatives, cosolvents, chelating agents, sweeteners, and water, which are palatable, alcohol-free, and sugar-free, with a shelf-life of at least 18 months.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If conventional oral liquid formulations of metoprolol tartrate are used, then the formulation can be administered orally, but the formulation lacks stability and has unacceptable shelf-life

Engineering Contradiction:
Improveformulation stabilityVSAvoidshelf-life
Core Design Contradiction:
Stability of the object's compositionVSDuration of action of stationary object

Solution Approach 1:

The patent applies parameter changes by adjusting the pH of the formulation to a specific range (2.5-5.5) and controlling the concentration of metoprolol tartrate (0.1-10% w/v) to achieve enhanced stability and extended shelf-life of at least 18 months

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by combining metoprolol tartrate with specific excipients including preservatives (sodium benzoate, parabens), cosolvents (propylene glycol, glycerine), chelating agents (disodium edetate), and sweeteners (sucralose, acesulfame potassium) to create a stable formulation system

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If tablet form of metoprolol is used, then the formulation is stable, but it is difficult for geriatric or seriously ill patients to swallow

Engineering Contradiction:
Improveease of administrationVSAvoidformulation stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent segments the tablet dosage form into a liquid dosage form that can be easily administered via oral syringe or dosing cup, making it accessible to geriatric and incapacitated patients while maintaining formulation stability through controlled pH and composition

Inventive Principle:
Principle #1Segmentation

3Ease of operation

If liquid formulation is developed for ease of administration, then palatability and ease of swallowing are improved, but stability and shelf-life deteriorate

Engineering Contradiction:
Improveease of administrationVSAvoidformulation reliability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent changes critical parameters including pH (2.5-5.5), metoprolol concentration (0.1-10% w/v), and adds chelating agents to prevent degradation, thereby achieving both ease of administration and formulation reliability with shelf-life of at least 18 months

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces intermediary substances including preservatives (sodium benzoate, parabens), chelating agents (disodium edetate), and cosolvents (propylene glycol, glycerine) that mediate between the active ingredient and the formulation environment to maintain stability while enabling liquid dosage form

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 formulations are chemically and physically stable, palatable, and have an extended shelf-life, allowing for precise dose adjustment and improved patient compliance, particularly in elderly and incapacitated individuals.

Implementation Method 1

one or more chelating agents

Methodology Applied
Scientific EffectChelation:

Implementation Method 2

one or more preservatives

Methodology Applied
Scientific EffectPreservation: Preservative

Implementation Method 3

one or more cosolvents

Methodology Applied
Scientific EffectCosolvation: Solvation

Data Source

PatentUS20250057789A1Stable oral liquid formulations containing metoprolol or salts thereof
Publication Date: 2025.02.20 RUBICON RES PTY LTD

AI summary

The present disclosure relates to stable oral liquid pharmaceutical formulations comprising metoprolol or pharmaceutically acceptable salts thereof, methods of manufacturing the same, as well as applications thereof including the use of the inventive formulations for treatment of angina, hypertension, and myocardial infarction.