Ophthalmic Composition Sterilization for Long Shelf-Life Combination Drops
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Solution Overview
Problem
Existing ophthalmic pharmaceutical compositions with multiple active ingredients require separate administration, leading to cumbersome processes and low patient adherence, and there is a need for formulations that remain stable for extended periods during post-operative care.
Innovation Solution
A method involving autoclaving a first phase composition and sterile-filtering or autoclaving a second phase composition, followed by aseptic combination, results in a stable ophthalmic pharmaceutical composition with a shelf life of at least 90 days at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If multiple active ingredients are combined in one ophthalmic formulation, then patient adherence and ease of administration are improved, but formulation stability during storage deteriorates
Solution Approach 1:
The formulation is divided into two separate phases: a lipid phase containing the steroid (prednisolone acetate) and a water phase containing the fluoroquinolone (moxifloxacin) and NSAID (bromfenac). Each phase is sterilized separately and then combined aseptically, allowing each ingredient to remain stable in its own environment while enabling combined administration in a single drop.
Solution Approach 2:
The patent introduces specific excipients that act as intermediaries to maintain stability: sodium acetate and polyoxyethylene sorbitan monooleate in the lipid phase, and sodium phosphate, sodium metabisulfite, edetate disodium, boric acid, and sodium borate in the water phase. These intermediaries prevent degradation and maintain compatibility between the two phases during storage.
2Reliability
If all ingredients are autoclaved together, then sterilization is achieved, but active ingredient degradation increases
Solution Approach 1:
The sterilization process is segmented into separate treatments for the lipid phase and water phase. The lipid phase is autoclaved separately from the water phase, which is then sterile-filtered or autoclaved. This prevents thermal degradation of heat-sensitive active ingredients while still achieving complete sterilization of the final combined formulation through aseptic combination.
Solution Approach 2:
The active ingredients are incorporated into their respective phases before sterilization, and each phase is sterilized separately in advance. The lipid phase is autoclaved first, then the water phase is sterilized, and finally they are combined aseptically. This preliminary separate sterilization prevents degradation that would occur if all ingredients were exposed to autoclaving together.
3Duration of action of stationary object
If the formulation is designed for long-term storage, then shelf life is extended, but requires complex stabilization methods
Solution Approach 1:
The formulation is segmented into two phases that can be separately sterilized and stored. This segmentation simplifies the stabilization approach by allowing each phase to be optimized independently for its specific ingredients, rather than requiring a complex single-phase stabilization system for all ingredients together.
Solution Approach 2:
The patent specifies precise parameter ranges to achieve long shelf life: pH between 7.5-9.0, autoclaving at 121°C for 30 minutes at 15-18 psi, and specific concentrations of excipients. These controlled parameter changes enable extended shelf life (at least 90 days at room temperature) without requiring overly complex stabilization methods.
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 method significantly extends the shelf life of the ophthalmic pharmaceutical composition, maintaining active ingredient concentrations and pH stability for up to 365 days, ensuring potency and microbial safety.
Implementation Method 1
autoclaving a first phase composition, autoclaving or sterile-filtering a second phase composition
Implementation Method 2
the autoclaving temperature is about 121° C., and the pressure is between about 15 and about 18 psi
Implementation Method 3
autoclaving or sterile-filtering a second phase composition
Implementation Method 4
combining the first phase composition and the second phase composition aseptically
Data Source
AI summary
The present disclosure relates to methods for extending the shelf life of a sterile ophthalmic pharmaceutical composition.