Amphiphile Particle Morphology Control via Thermal Processing
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Solution Overview
Problem
Existing methods for producing non-lamellar amphiphile-based particles often result in broad particle size distributions and a significant proportion of contaminant lamellar vesicular particles, which can lead to instability and variability in pharmacokinetics and efficacy, especially for intravenous administration.
Innovation Solution
A method involving heating lamellar and non-lamellar particles to an elevated temperature followed by cooling, which can convert at least 50% of lamellar particles to a non-lamellar form, thereby narrowing the particle size distribution and improving stability, is employed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional methods are used to produce non-lamellar amphiphile-based particles, then particles can be formed, but the particle size distribution becomes broad and contaminant lamellar vesicular particles are generated
Solution Approach 1:
The patent applies parameter changes by adjusting the ratio of water to amphiphile mixture (specifically using 1-10 volumes of water per volume of amphiphile mixture) and controlling the pH level to transform the particle morphology from lamellar to non-lamellar structures. This parameter optimization narrows the particle size distribution and eliminates contaminant lamellar vesicular particles, thereby improving both manufacturing precision and pharmacokinetic stability.
2Reliability
If lamellar particles are present in the dispersion, then the formulation can be prepared, but the stability and efficacy variability increases
Solution Approach 1:
The patent transforms lamellar particles into non-lamellar particles by changing key parameters including water-to-amphiphile ratio (1-10:1 volumes) and pH level adjustment. These parameter changes drive the morphological transformation that eliminates contaminant lamellar vesicular particles, simultaneously improving formulation stability and particle morphology control precision.
3Productivity
If non-lamellar particles are used for intravenous administration, then controlled release and loading capacity are enhanced, but particle size distribution must be narrowly controlled
Solution Approach 1:
The patent achieves narrow particle size distribution control while maintaining high loading capacity by optimizing the water-to-amphiphile ratio (1-10:1 volumes) and pH parameters. These parameter changes promote the formation of monodisperse non-lamellar particles with consistent sizes, enabling both enhanced productivity through improved loading capacity and manufacturing precision through narrow size distribution.
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
This approach results in a dispersion with a narrower, more stable particle size distribution and a higher proportion of non-lamellar particles, enhancing the controlled release and loading capacity of active agents, while maintaining stability over time.
Implementation Method 1
heating lamellar and non-lamellar particles to an elevated temperature followed by cooling, which can convert at least 50% of lamellar particles to a non-lamellar form
Implementation Method 2
heating said particles to an elevated temperature followed by cooling
Data Source
AI summary
The present invention provides a method for forming a dispersion comprising non-lamellar amphiphile particles having improved phase behavior, particle size distribution and/or storage stability, said method comprising forming a dispersion of lamellar and optionally non-lamellar particles comprising at least one structuring agent in a polar solvent, heating said particles to an elevated temperature, followed by cooling, wherein said heating is to a temperature and for a period sufficient to provide, after cooling, a measurable improvement in phase behavior, particle size distribution and/or storage stability.