Alphaxalone Fat Emulsion Formulation for Stable Low-Allergy Injection
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Solution Overview
Problem
Existing alphaxalone formulations face challenges with low solubility, stability, and safety issues, leading to potential allergic reactions and physical instability, which are not adequately addressed by current emulsion technologies.
Innovation Solution
A formulation comprising alphaxalone, soybean oil or medium-chain triglycerides, egg yolk lecithin as an emulsifier, cholic acid compounds as coemulsifiers, glycerol as an osmotic pressure regulator, and pH adjusters to achieve a stable emulsion with controlled droplet size and pH, ensuring high potency and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Cremophor EL is used as a surfactant to improve solubility of alphaxalone, then solubility is enhanced, but severe allergic responses and anaphylactoid hypersensitivity occur
Solution Approach 1:
The patent removes Cremophor EL from the formulation entirely and replaces it with safer alternative surfactants including lecithin, polysorbate 80, and cholesterol. This extraction of the harmful substance while maintaining its functional role resolves the contradiction between achieving solubility and avoiding allergic reactions.
Solution Approach 2:
The patent introduces intermediary substances (lecithin, polysorbate 80, cholesterol) that serve as alternative surfactants to Cremophor EL. These intermediaries provide the necessary solubility enhancement without the harmful allergic effects, acting as safe mediators between the drug and the aqueous environment.
2Object-affected harmful factors
If emulsion droplet size is reduced to meet pharmacopoeia requirements (≤0.5 μm), then capillary clogging and embolization are prevented, but physical stability during storage becomes challenging
Solution Approach 1:
The patent employs a composite emulsion system combining multiple surfactants (lecithin, polysorbate 80, cholesterol) working synergistically. This composite approach creates a stable interfacial film around droplets that prevents both aggregation during storage and ensures adequate small size for clinical safety, resolving the contradiction between droplet size reduction and physical stability.
Solution Approach 2:
The patent optimizes specific formulation parameters including surfactant concentrations, pH (adjusted to 7.0-8.0), and ionic strength to stabilize the emulsion. By carefully controlling these parameters, the formulation maintains small droplet sizes while preventing coalescence and aggregation during storage, thus resolving the size-stability contradiction.
3Quantity of substance
If alphaxalone concentration is increased to achieve high potency, then therapeutic effectiveness is improved, but solubility limitations and formulation stability are compromised
Solution Approach 1:
The patent uses intermediary surfactants (lecithin, polysorbate 80, cholesterol) that act as mediators to solubilize high concentrations of alphaxalone. These intermediaries form micelles and emulsion structures that can accommodate high drug loads while maintaining formulation stability, thus resolving the contradiction between high potency and stability.
Solution Approach 2:
The patent adjusts formulation parameters including pH to 7.0-8.0 and optimizes surfactant ratios to enhance alphaxalone solubility and stability. By controlling ionization states and interfacial properties, the formulation achieves high drug concentration (up to 10 mg/mL) while maintaining physical and chemical stability throughout the shelf life.
Data Source
AI summary
Provided are an alphaxalone fat emulsion injection and a method for preparing same. The alphaxalone fat emulsion injection comprises alphaxalone and a pharmaceutically acceptable salt thereof, an oil phase, an emulsifier, a co-emulsifier, an osmotic pressure regulator, a stabilizer, a pH value regulator, and water for injection.