Clevidipine Emulsion Antimicrobial Stability
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Solution Overview
Problem
Clevidipine oil-in-water emulsion formulations are prone to microbial contamination, requiring strict aseptic handling and frequent vial replacements, which increases healthcare costs and inefficiencies.
Innovation Solution
A stable clevidipine emulsion formulation incorporating an antimicrobial agent like EDTA, a co-emulsifier such as oleic acid, and an antioxidant like sodium ascorbate, combined with glycerin to inhibit microbial growth and maintain stability, reducing the risk of contamination and extending the formulation's usability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If clevidipine is formulated as an oil-in-water emulsion to improve solubility, then solubility is improved, but the formulation becomes prone to microbial contamination
Solution Approach 1:
The patent introduces antimicrobial agents (benzyl alcohol, phenol, methylparaben, propylparaben, or their combinations) as intermediary substances that mediate between the emulsion formulation and microbial contaminants. These agents actively inhibit microbial growth in the oil-in-water emulsion, allowing the formulation to maintain improved solubility while protecting against the harmful microbial contamination effect
Solution Approach 2:
The patent creates a composite emulsion formulation by combining clevidipine with multiple components including oils (soybean oil, medium-chain triglycerides), emulsifiers (egg yolk phospholipids), and antimicrobial agents. This composite structure integrates the solubility-enhancing properties of the oil phase with the antimicrobial protection, resolving the contradiction between improved solubility and microbial susceptibility
2Object-affected harmful factors
If strict aseptic technique and frequent vial replacements are implemented to prevent microbial contamination, then microbial contamination is reduced, but healthcare costs and operational complexity increase
Solution Approach 1:
The patent enables the formulation to protect itself against microbial contamination through the inclusion of antimicrobial agents. The formulation becomes self-protecting, eliminating the need for external interventions such as strict aseptic handling procedures and frequent vial replacements, thereby reducing operational complexity while maintaining protection against microbial contamination
Solution Approach 2:
The antimicrobial agents are incorporated into the formulation during manufacturing, providing preliminary protection against microbial contamination before the product reaches the healthcare setting. This pre-established protection eliminates the need for complex ongoing protective measures during storage and administration
3Object-affected harmful factors
If strict aseptic technique and frequent vial replacements are implemented to prevent microbial contamination, then microbial contamination is reduced, but time consumption and operational inefficiency increase
Solution Approach 1:
The formulation's built-in antimicrobial protection allows it to defend itself against microbial contamination without requiring time-consuming manual interventions. Healthcare providers no longer need to spend time on frequent vial replacements and strict aseptic manipulations, as the formulation maintains its stability and protection throughout the intended usage period
4Object-affected harmful factors
If frequent vial replacements are performed to prevent microbial contamination, then microbial contamination is reduced, but drug wastage increases
Solution Approach 1:
The antimicrobial agents are incorporated into the formulation during manufacturing, providing preliminary and sustained protection against microbial contamination. This allows the formulation to remain stable and safe for use throughout its intended shelf life and beyond, eliminating the need for conservative disposal timelines and reducing drug wastage from frequent vial replacements
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 effectively retards microbial growth for at least 24 hours, reducing the risk of contamination and minimizing wastage, while maintaining clevidipine's stability and efficacy, thus enhancing handling ease and cost-effectiveness.
Implementation Method 1
further comprises an amount of EDTA sufficient to inhibit growth of microorganisms in the formulation
Implementation Method 2
the emulsion is further stabilized by the co-emulsifier oleic acid
Implementation Method 3
an antioxidant like sodium ascorbate, combined with glycerin to inhibit microbial growth and maintain stability
Implementation Method 4
The tonicity of emulsion is adjusted with glycerin
Implementation Method 5
clevidipine is dispersed or dissolved in a lipid, such as soy bean oil, which in turn is emulsified with egg yolk phospholipids in water
Data Source
Figure 1
AI summary
Pharmaceutical formulations comprising clevidipine and an antimicrobial agent exhibit a reduced propensity for microbial growth and provide increased convenience to health care workers administering clevidipine-containing formulations to patients.