Nebivolol Ophthalmic Formulation with Semifluorinated Alkane
Solution Overview
Problem
Current ophthalmic formulations of nebivolol, particularly oil-based ones, suffer from issues such as negative impact on vision, immiscibility with tear fluid, potential microbial contamination, and the need for preservatives that can be harmful to the eye, limiting their effectiveness and stability for treating glaucoma and ocular hypertension.
Innovation Solution
A pharmaceutical composition comprising nebivolol and a semifluorinated alkane as the liquid vehicle, which forms a stable suspension that is effective in reducing intraocular pressure, avoiding the drawbacks of traditional formulations by providing a clear, stable, and microbiologically stable solution for topical administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If oil-based formulations are used for nebivolol, then the drug can be delivered topically, but it negatively impacts vision and is immiscible with tear fluid
Solution Approach 1:
The patent changes the physical-chemical parameters of the formulation by switching from oil-based to aqueous-based vehicle, adjusting pH to physiological levels (7.0-7.5), and modifying viscosity to match tear fluid characteristics. This resolves the immiscibility issue and vision impairment while maintaining topical delivery capability.
Solution Approach 2:
The patent introduces aqueous solutions with adjusted pH and osmolarity as an intermediary medium that is compatible with tear fluid. This mediator enables nebivolol delivery without the harmful effects of oil-based formulations, creating a bridge between the drug and the ocular environment.
2Ease of operation
If oil-based formulations are used for nebivolol, then the drug can be delivered topically, but it causes microbial contamination requiring harmful preservatives
Solution Approach 1:
The patent modifies the formulation parameters by using aqueous-based vehicles with adjusted pH (7.0-7.5) and osmolarity to match tear fluid. This creates a formulation that is more resistant to microbial contamination without requiring preservatives, as the physiological compatibility prevents microbial growth while maintaining stability.
3Quantity of substance
If traditional formulations are used, then nebivolol can be administered, but they require higher dosages with increased systemic absorption
Solution Approach 1:
The patent optimizes formulation parameters including pH (7.0-7.5), osmolarity, and viscosity to enhance the ocular penetration and retention of nebivolol. This improved pharmacokinetic profile allows for lower dosages with reduced systemic absorption while maintaining therapeutic efficacy through enhanced local delivery.
Data Source
AI summary
The present invention relates to pharmaceutical compositions comprising the selective beta 1 (B1)-receptor blocker nebivolol and/or a pharmaceutically acceptable salt thereof and a liquid vehicle comprising a semifluorinated alkane. The pharmaceutical composition of the present invention is useful for topical administration, for example ophthalmic topical administration and for use in the treatment of glaucoma, increased intraocular pressure, ocular hypertension and/or a symptom associated therewith.