Clevidipine Nanoparticles for Ambient Stability and Immediate Release
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Solution Overview
Problem
Existing clevidipine formulations, such as the Cleviprex emulsion, have limitations including microbial growth support, high lipid content, refrigeration requirements, and unsuitable pharmacokinetics for immediate release applications, necessitating a stable, ambiently stable, and low-lipid formulation for parenteral use.
Innovation Solution
Development of clevidipine nanoparticles stabilized by electrostatic and stearic stabilization using combinations of water-soluble and water-insoluble excipients, produced via a microjet reactor, ensuring immediate release and stability at ambient temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If clevidipine is formulated as an oil-in-water emulsion (Cleviprex), then chemical stability is improved, but microbial growth support and high lipid content occur
Solution Approach 1:
The patent changes the formulation parameters by transitioning from a conventional oil-in-water emulsion to a nanoparticle dispersion system. This parameter change allows the formulation to achieve chemical stability through nanoparticle encapsulation while eliminating the need for high lipid content and microbial growth retardants, thereby resolving the contradiction between stability and harmful factors.
Solution Approach 2:
The patent employs composite nanoparticle structures combining clevidipine with specific excipients (such as phospholipids, cholesterol, and polymers) to create a stable dispersion system. This composite approach provides chemical stability through the nanoparticle matrix while avoiding the harmful effects of traditional emulsion formulations, including microbial growth support and excessive lipid content.
2Stability of the object's composition
If clevidipine is formulated as an oil-in-water emulsion (Cleviprex), then chemical stability is improved, but refrigeration requirements increase
Solution Approach 1:
The patent changes the physical state and formulation parameters by creating a nanoparticle dispersion that remains stable at ambient temperatures. This parameter change eliminates the need for refrigeration while maintaining chemical stability, as the nanoparticle structure provides protection against degradation without requiring cold-chain storage.
3Stability of the object's composition
If conventional nanoparticle formulations (solid lipid nanoparticles, albumin stabilized nanoparticles, or liposomes) are used, then stability in water at ambient temperatures is improved, but immediate release pharmacokinetics are compromised
Solution Approach 1:
The patent applies local quality by creating nanoparticle formulations with specific surface properties and compositions that differ from conventional uniform nanoparticle structures. By controlling the local composition and surface characteristics of the nanoparticles, the formulation achieves both ambient stability and immediate release pharmacokinetics, as the localized structural features enable rapid drug release upon administration.
4Stability of the object's composition
If high lipid content is used in Cleviprex formulation, then chemical stability is improved, but lipid load and restrictions in patients with hyperlipidemia increase
Solution Approach 1:
The patent fundamentally changes the formulation parameters by replacing high-lipid emulsion systems with a nanoparticle dispersion system. This parameter change maintains chemical stability through nanoparticle encapsulation while dramatically reducing lipid content, thereby eliminating restrictions for patients with hyperlipidemia and reducing overall lipid load.
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 nanoparticles provide stable, immediate release of clevidipine at ambient temperatures, reducing microbial growth risks and lipid load, and maintaining pharmacokinetic properties, facilitating easier handling and broader clinical use.
Implementation Method 1
colliding clevidipine, or a pharmaceutically acceptable salt thereof, and said at least one excipient in a microjet reactor
Implementation Method 2
formed by colliding clevidipine, or a pharmaceutically acceptable salt thereof, and said at least one excipient in a microjet reactor
Implementation Method 3
stabilized by electrostatic and stearic stabilization using combinations of water-soluble and water-insoluble excipients
Implementation Method 4
stabilized by electrostatic and stearic stabilization using combinations of water-soluble and water-insoluble excipients
Implementation Method 5
ensuring immediate release and stability at ambient temperatures
Data Source
AI summary
Provided is a pharmaceutical composition comprising clevidipine in a sterile, ready to use, physically stable, aqueous dispersion of nanoparticles that stabilizes clevidipine against formation of impurities and is suitable for parenteral administration.