Brinzolamide Ophthalmic Solution Sterilization via Surfactant Mediation
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Solution Overview
Problem
Existing ophthalmic compositions of brinzolamide, particularly in suspension form, face challenges with sterilization methods that introduce degradation or result in large needle-shaped crystals, which are harmful to the eyes, and there is a need for an aqueous solution formulation that effectively lowers intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
Innovation Solution
An aqueous ophthalmic solution comprising brinzolamide, solubilizing agents like hydroxy-propyl-β-cyclodextrin and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, isotonic agents, chelating agents, and buffering agents, with a concentration of 0.5-0.95% brinzolamide, which is dissolved in the solution to ensure safety and efficacy, and optionally includes viscosity-enhancing polymers and purified water.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional sterilization methods (autoclaving) are used for brinzolamide suspension, then sterilization is achieved, but brinzolamide recrystallizes as large needle-shaped crystals that are harmful to the eyes
Solution Approach 1:
A surfactant (polysorbate 80) is introduced as an intermediary substance to prevent the formation of large harmful crystals during sterilization. The surfactant adsorbs at the crystal surface, modifying the crystallization process to produce smaller, safer particles while maintaining sterilization efficacy.
Solution Approach 2:
The invention changes the physical-chemical parameters of the system by introducing a surfactant that alters the surface tension and crystallization behavior of brinzolamide. This parameter change transforms the crystallization process from forming large harmful needles to forming smaller safe particles during autoclaving.
2Reliability
If dry heat sterilization is used for brinzolamide suspension, then sterilization is achieved, but the material melts
Solution Approach 1:
A surfactant is introduced as a protective intermediary that stabilizes the brinzolamide particles during dry heat sterilization. The surfactant forms a protective layer around the particles, preventing direct thermal contact and melting while allowing sterilization to proceed.
3Reliability
If ethylene oxide or gamma irradiation sterilization is used for brinzolamide suspension, then sterilization is achieved, but unacceptable degradation products are introduced
Solution Approach 1:
The invention converts the potentially harmful sterilization process into a beneficial one by using autoclaving (moist heat) combined with surfactant protection. This approach eliminates the need for ethylene oxide or gamma irradiation, avoiding degradation products while achieving complete sterilization through the controlled crystallization process.
4Ease of operation
If brinzolamide is administered as large needle-shaped crystals, then administration is simple, but the crystals damage the eyes
Solution Approach 1:
A surfactant serves as a protective intermediary that modifies the crystal morphology and size during sterilization. This ensures that the administered form consists of small, safe particles rather than large harmful needles, maintaining ease of administration while eliminating eye damage risk.
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 solution provides equivalent efficacy in reducing intraocular pressure compared to traditional 1.0% brinzolamide ophthalmic suspension, with improved safety by dissolving brinzolamide and maintaining stability, and is suitable for use as eye drops, addressing the limitations of previous formulations.
Implementation Method 1
An aqueous ophthalmic solution comprising brinzolamide, solubilizing agents like hydroxy-propyl-β-cyclodextrin and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
Data Source
AI summary
The present invention relates to an aqueous ophthalmic solution for treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma, the solution comprising at least 0.5 w/v % brinzolamide dissolved in the solution; hydroxy-propyl-β-cyclodextrin; polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; and water and/or the process for preparation thereof.