Aqueous Quinazolinone Eye Suspension for Hydrophobic Drug Stability
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Solution Overview
Problem
Formulating hydrophobic compounds into stable, aqueous ophthalmic compositions for topical treatment of ocular surface conditions, particularly ocular surface pain, is challenging due to agglomeration issues that affect stability and quality.
Innovation Solution
An aqueous formulation comprising 4-(7-Hydroxy-2-isopropyl-4-oxo-4H-quinazolin-3-yl)-benzonitrile or its salts, co-crystals, or polymorphs, combined with excipients such as surfactants, suspending agents, tonicity agents, buffers, and preservatives, to create a stable suspension for topical application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If hydrophobic compounds are formulated into aqueous ophthalmic compositions, then topical administration becomes non-invasive and convenient, but agglomeration occurs causing stability and quality issues
Solution Approach 1:
The patent employs surfactants as intermediary substances to mediate between the hydrophobic compound and aqueous environment. The surfactant molecules have hydrophilic heads that interact with water and hydrophobic tails that interact with the drug compound, forming stable micellar structures that prevent agglomeration while maintaining solubility and formulation stability.
Solution Approach 2:
The formulation creates a composite system combining hydrophobic compound, surfactant, and aqueous components into a stable emulsion or micellar dispersion. This composite structure allows the hydrophobic drug to be effectively delivered in an aqueous vehicle without phase separation or precipitation, resolving the contradiction between solubility and stability.
2Adaptability or versatility
If hydrophobic compounds are used in aqueous formulations, then ocular surface pain can be treated topically, but agglomeration causes quality issues
Solution Approach 1:
The patent modifies key formulation parameters including surfactant concentration, pH, ionic strength, and temperature to optimize the stability and quality of the aqueous formulation. By carefully controlling these parameters, the formulation maintains consistent drug distribution and prevents agglomeration, ensuring both treatment applicability and manufacturing quality.
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 formulation maintains stability and effectiveness for up to 18 months, reducing ocular surface pain by 10-25% within hours of application and improving symptoms of dry eye disease.
Implementation Method 1
one or more excipients selected from the group consisting of a surfactant, a suspending agent
Implementation Method 2
the 4-(7-Hydroxy-2-isopropyl-4-oxo-4H-quinazolin-3-yl)-benzonitrile (compound I) or a salt, co-crystal, or polymorph thereof is present in the formulation as a suspension
Data Source
AI summary
The present invention provides formulations of 4-(7-hydroxy-2-isopropyl-4-oxo-4H-quinazolin-3-yl)-benzonitrile (compound I) and methods for treating ocular surface pain by administering such formulations. The present invention also provides methods for treating dry eye disease and ocular hyperemia by administering formulations of 4-(7-hydroxy-2-isopropyl-4-oxo-4 H-quinazolin-3-yl)-benzonitrile.