Ophthalmic Composition Using Macrogol 15 Hydroxystearate
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Solution Overview
Problem
Current ophthalmic compositions for treating elevated intraocular pressure have low ocular bioavailability due to rapid precorneal drug elimination and systemic absorption, limiting their effectiveness.
Innovation Solution
An aqueous ophthalmic composition comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester as the active ingredient, combined with macrogol 15 hydroxystearate as the sole solubilizing agent, to enhance ocular permeability and absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional aqueous ophthalmic solutions are used, then the formulation is simple and stable, but ocular bioavailability is very low due to rapid precorneal drug elimination and systemic absorption
Solution Approach 1:
The patent introduces macrogol 15 hydroxystearate as an intermediary substance that mediates between the hydrophobic prostamide active ingredient and the aqueous ophthalmic solution. This surfactant forms micelles that solubilize the drug and enhance its penetration through the corneal epithelium, thereby improving ocular bioavailability while reducing precorneal elimination
Solution Approach 2:
The patent changes the physical-chemical parameters of the formulation by using macrogol 15 hydroxystearate to alter the solubility, surface tension, and penetration characteristics of the ophthalmic solution, enabling better drug delivery to the ocular surface and improved bioavailability
2Ease of operation
If eye drops are administered topically, then the administration route is non-invasive and easy, but ocular absorption is limited by the corneal epithelial barrier and rapid drainage
Solution Approach 1:
Macrogol 15 hydroxystearate acts as a penetration enhancer that facilitates the transfer of the prostamide drug across the corneal epithelial barrier. The surfactant interacts with the lipid components of the corneal membrane, creating pathways for enhanced drug absorption while maintaining the simplicity of topical drop administration
Solution Approach 2:
The formulation is designed to pre-condition the ocular surface environment by the surfactant macrogol 15 hydroxystearate, which prepares the corneal epithelium for enhanced drug penetration before the active ingredient is delivered, thereby improving absorption efficiency
3Ease of operation
If some prostaglandin eye drop formulations are used, then they can be stable at room temperature, but they require cold storage to preserve active ingredient level
Solution Approach 1:
Macrogol 15 hydroxystearate serves as a stabilizing intermediary that protects the prostamide active ingredient from degradation. The surfactant forms protective micellar structures that shield the drug molecule from hydrolysis and other degradation pathways, enabling stable storage at room temperature without cold chain requirements
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 achieves higher ocular permeability and enhanced ocular absorption of the active compound, leading to improved efficacy in reducing intraocular pressure, while also providing chemical and physical stability at room temperature.
Implementation Method 1
an aqueous ophthalmic composition comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester as the active ingredient, combined with macrogol 15 hydroxystearate as the sole solubilizing agent
Data Source
AI summary
The present invention relates to a preservative free ophthalmic aqueous composition in the form of solution comprising 0.005% to 0.18% w/w hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester, from 0.5% w/w to 1.5% w/w macrogol 15 hydroxystearate, wherein macrogol 15 hydroxystearate is the only solubilizing agent.