Macrogol 15 Hydroxystearate Ophthalmic Solubilizer

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Solution Overview

Problem

Topically applied ophthalmic formulations face challenges due to poor aqueous solubility of active pharmaceutical ingredients (APIs), limiting the maximum drug dose that can be formulated as a solution, necessitating strategies to enhance solubility.

Innovation Solution

An ophthalmic composition comprising an active pharmaceutical ingredient, macrogol 15 hydroxystearate, and benzalkonium chloride at a concentration of 10 to 200 ppm, which improves solubility and stability of the API, preventing oxidative degradation and maintaining effectiveness across various storage conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If polysorbate 80 is used as a solubilizer to increase API solubility, then the solubility of the active pharmaceutical ingredient is improved, but oxidative degradation of the API occurs

Engineering Contradiction:
ImproveAPI solubilityVSAvoidAPI stability
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent replaces polysorbate 80 with macrogol 15 hydroxystearate, changing the chemical parameter of the solubilizer to eliminate oxidative degradation while maintaining API solubility. This substitution fundamentally alters the chemical composition to resolve the contradiction between solubility enhancement and stability preservation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs macrogol 15 hydroxystearate as a stable, non-oxidizing alternative to polysorbate 80, effectively replacing a problematic substance with a superior one that provides the same solubilizing function without the harmful oxidative side effects.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If the concentration of benzalkonium chloride is reduced to maintain API stability, then oxidative degradation is prevented, but preservative effectiveness may be compromised

Engineering Contradiction:
ImproveAPI stabilityVSAvoidpreservative effectiveness
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces macrogol 15 hydroxystearate as an intermediary substance that mediates between the preservative benzalkonium chloride and the API. This intermediary protects the API from oxidative degradation by benzalkonium chloride, allowing the use of lower preservative concentrations while maintaining both stability and effectiveness.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the potentially harmful oxidative effect of benzalkonium chloride into a beneficial protective effect by using macrogol 15 hydroxystearate to prevent degradation. The same preservative that could cause harm is instead used at reduced concentrations with protection provided by the macrogol compound.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 composition effectively increases the solubility and stability of APIs, allowing for higher therapeutic doses in topical ophthalmic formulations, thereby enhancing treatment efficacy for conditions like ocular hypertension, glaucoma, and dry eye.

Implementation Method 1

macrogol 15 hydroxystearate...improves solubility of the API

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 2

macrogol 15 hydroxystearate...preventing oxidative degradation

Methodology Applied
Scientific EffectAntioxidation: Oxidation

Data Source

PatentEP2726060B1Macrogol 15 hydroxystearate formulations
Publication Date: 2019.12.25 ALLERGAN INC
  • EP2726060B1 patent drawingFigure 1
  • EP2726060B1 patent drawingFigure 2A~2B
  • EP2726060B1 patent drawingFigure 2C~2D

AI summary

Provided herein are compositions, which include an active pharmaceutical ingredient and macrogol 15 hydroxystearate, and methods for using the same for treating diseases or disorder.