Ophthalmic Emulsion Phase Separation for Extended Retention

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Solution Overview

Problem

Prior ophthalmic compositions suffer from inefficient delivery of pharmaceutical ingredients to the eye due to short duration on the ocular surface, leading to frequent application needs and discomfort in treating dry eye conditions.

Innovation Solution

An ophthalmic pharmaceutical composition comprising a carboxyvinyl polymer, a polyanionic polysaccharide, a medium-chain triglyceride, and water, forming an oil phase-in-water phase emulsion, which is gentle on the ocular surface and provides extended lubrication by breaking into separate phases upon dilution with tears, reducing evaporation and enhancing retention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If the viscosity of the ophthalmic composition is increased to extend duration on the eye, then the duration of action is improved, but the composition becomes sticky and uncomfortable for the patient

Engineering Contradiction:
Improveduration on eyeVSAvoidcomfortability
Core Design Contradiction:
Duration of action of moving objectVSEase of operation

Solution Approach 1:

The composition is divided into two distinct phases: an aqueous phase containing hydrophilic polymers and lipids, and an oil phase containing hydrophobic polymers and lipids. This segmentation allows each phase to perform specific functions - the aqueous phase provides initial lubrication and comfort, while the oil phase provides extended retention and reduces evaporation, thereby resolving the contradiction between duration and comfort.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses a composite emulsion system combining both hydrophilic and hydrophobic polymers and lipids in a single composition. This composite structure enables the composition to exhibit both the comfort of aqueous-based formulations and the extended duration of oil-based formulations, simultaneously addressing both requirements of the technical contradiction.

Inventive Principle:
Principle #40Composite materials

2Reliability

If tear substitutes are applied repeatedly throughout the day to maintain lubrication, then the ocular surface is kept moist, but the frequency of application increases and becomes inconvenient

Engineering Contradiction:
Improvelubrication maintenanceVSAvoidapplication frequency
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The composition dynamically adjusts its behavior on the ocular surface through phase separation. Upon application, the emulsion breaks into aqueous and oil phases that work synergistically to provide extended lubrication. The oil phase forms a protective barrier that slowly releases hydrophobic polymers and lipids, maintaining ocular surface moisture for extended periods, thereby reducing the frequency of applications needed to maintain reliability.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The dual-phase composition provides continuous lubrication through the coordinated action of both phases. The aqueous phase provides immediate lubrication while the oil phase provides sustained protection against evaporation. This continuous action eliminates the need for frequent reapplication, as the composition maintains its useful function throughout the day without requiring multiple dosing events.

Inventive Principle:
Principle #20Continuity of useful action

3Quantity of substance

If the composition remains as a stable emulsion on the eye, then delivery is enhanced, but the composition does not break down to release active ingredients effectively

Engineering Contradiction:
Improveactive ingredient deliveryVSAvoidemulsion stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The composition exhibits dynamic stability - it remains stable during storage and handling as a uniform emulsion, ensuring even distribution and enhanced delivery. Upon application to the eye, the emulsion dynamically breaks down into separate aqueous and oil phases, releasing the active ingredients embedded in each phase. This dynamic behavior resolves the contradiction by providing both stable delivery and effective release.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The composition undergoes parameter changes in its physical state upon application. The emulsion transitions from a stable, uniform state during storage to a separated state on the ocular surface. This parameter change is triggered by the specific conditions on the eye (tears, temperature, mechanical stress) and enables the release of active ingredients while maintaining enhanced delivery through the controlled breakdown of the emulsion structure.

Inventive Principle:
Principle #35Parameter changes

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 offers enhanced delivery and prolonged retention of active ingredients, reducing the frequency of application and alleviating dry eye symptoms with improved comfort and efficacy.

Implementation Method 1

forming an oil phase-in-water phase emulsion, which is gentle on the ocular surface and provides extended lubrication by breaking into separate phases upon dilution with tears

Methodology Applied
Scientific EffectPhase separation: Phase Change

Data Source

PatentEP2814463B1Ophthalmic pharmaceutical compositions and methods of making and using same
Publication Date: 2016.05.18 BAUSCH & LOMB INC
  • EP2814463B1 patent drawingFigure 1
  • EP2814463B1 patent drawingFigure 2
  • EP2814463B1 patent drawingFigure 3

AI summary

A stable ophthalmic pharmaceutical composition for relief, treatment, control, alleviation, or prevention of a pathological ocular condition of the eye comprises: (a) a first polymer, a viscosity of which changes with a change in a concentration of an electrolyte, such as a salt, when added to said first polymer; (b) a second polymer that is different from the first polymer and can modify the viscosity of the first polymer; and (c) an oil. In some embodiments, the composition further comprises a non-ionic surfactant. The composition can form a stable oil-in-water emulsion on storage, but separate into an oil phase and a water phase when applied in the eye. The emulsion can comprises an ophthalmic active pharmaceutical ingredient dissolved in the oil or water phase. The emulsion can provide enhanced stability to said active pharmaceutical ingredient.