Rapamycin Self-Microemulsifying Injection for Solubility and Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing RAPA injections face challenges with low solubility and poor stability, which affect their efficacy in clinical applications, particularly in cancer treatment.
Innovation Solution
A RAPA self-microemulsifying injection is developed, comprising a drug stock solution with a drug solvent, antioxidant, and diluent containing a surfactant and water, which self-assembles into a microemulsion encapsulating RAPA, using PEG stearate as the surfactant to enhance solubility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If RAPA is formulated in conventional injection forms, then the preparation process is simple, but the solubility and stability of RAPA are poor
Solution Approach 1:
The patent uses a composite microemulsion system comprising multiple components: surfactants (Tween 80, Span 80), co-surfactants (PEG 400, propylene glycol), and oil phase (olive oil). This composite formulation creates a stable microemulsion that simultaneously improves RAPA solubility and stability while maintaining a relatively simple preparation process involving only mixing and ultrasonic treatment.
2Quantity of substance
If RAPA concentration in injection is increased, then treatment efficacy improves, but solubility limitations prevent achieving high concentrations
Solution Approach 1:
The patent achieves high RAPA concentration (up to 60 mg/mL) by changing the physical-chemical parameters of the formulation system. The microemulsion structure with optimized surfactant-co-surfactant-oil ratios creates a solubilizing environment that can accommodate high drug loads. Specifically, the combination of Tween 80 and Span 80 in controlled proportions, along with PEG 400 and propylene glycol as co-surfactants, enables exceptional solubility enhancement.
3Device complexity
If conventional solubilization methods are used, then the formulation is simple, but RAPA stability remains poor
Solution Approach 1:
The patent introduces multiple intermediary substances that mediate between RAPA and the aqueous environment: surfactants (Tween 80, Span 80) that form micellar structures, co-surfactants (PEG 400, propylene glycol) that stabilize the interface, and olive oil that provides an oil phase for drug incorporation. These intermediaries collectively enhance RAPA stability without requiring complex preparation equipment or processes.
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 RAPA self-microemulsifying injection significantly improves solubility to 60 mg/mL and stability, allowing for high-concentration intravenous administration, reducing allergic reactions and maintaining stability for clinical use.
Implementation Method 1
after the stock solution is diluted with the diluent, the solution is self-assembled into a microemulsion under the action of the surfactant
Implementation Method 2
the solution is self-assembled into a microemulsion under the action of the surfactant, and the RAPA is encapsulated in the microemulsion
Implementation Method 3
The drug solvent includes absolute ethanol and a latent solvent... The drug solvent of the present disclosure is a mixed solvent of two or more solvents in different proportions to dissolve RAPA, which can greatly improve the solubility of RAPA
Data Source
AI summary
A rapamycin (RAPA) self-microemulsifying injection includes a drug stock solution and a diluent. The drug stock solution includes a drug solvent, an antioxidant, and RAPA, and the diluent includes a surfactant and water. RAPA is dissolved in the drug solvent. After the stock solution is diluted with the diluent, the solution is self-assembled into a microemulsion under the action of a surfactant, and RAPA is encapsulated in the microemulsion, which improves the solubility and stability of RAPA.