Self-Dispersing Non-Lamellar Lipid Compositions
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Solution Overview
Problem
Current methods for forming non-lamellar phase particles require high energy input and specialized equipment, making them impractical for point-of-care applications and unstable for storage, especially when incorporating sensitive active agents like proteins and peptides.
Innovation Solution
A composition comprising monoacyl lipids, diacyl glycerols, tocopherols, and fragmentation agents that self-disperse to form colloidal non-lamellar particles upon contact with an aqueous fluid, eliminating the need for high energy techniques and allowing for on-demand particle formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If high energy input methods (ultrasonication, homogenisation, high pressure filtration) are used to disperse non-lamellar phases, then particle formation is achieved, but the process requires specialised apparatus and high energy input, making it impractical for point-of-care applications
Solution Approach 1:
The composition is formulated to self-disperse into non-lamellar particles upon contact with aqueous fluid without requiring external energy input or specialised equipment. The amphiphilic compounds and fragmentation agents work together to automatically form the desired particle structure when mixed with water or body fluids, enabling point-of-care preparation.
Solution Approach 2:
The invention changes the physical-chemical parameters of the system by using specific ratios of amphiphilic compounds with different spontaneous curvatures and incorporating fragmentation agents. This parameter optimization allows the system to transition from requiring high-energy dispersion to spontaneous self-dispersion under physiological conditions.
2Reliability
If high energy dispersion methods are used, then non-lamellar particles are formed, but the dispersions are unstable for storage and transport, especially when incorporating sensitive active agents like proteins and peptides
Solution Approach 1:
The composition is pre-formulated with the optimal combination of amphiphilic compounds and fragmentation agents before use. This preliminary preparation ensures that when the composition contacts aqueous fluid, it immediately forms stable non-lamellar particles that protect sensitive active agents, eliminating the need for post-preparation stabilization steps.
Solution Approach 2:
The fragmentation agents act as intermediaries that facilitate the formation of non-lamellar structures while protecting sensitive active agents. These agents mediate between the amphiphilic compounds and the active agents, enabling stable particle formation without exposing proteins and peptides to damaging high-energy processes.
3Quantity of substance
If conventional amphiphile formulations are used, then both polar and apolar compounds can be solubilised, but they form lamellar structures with lower internal surface area and less tuneable interior space-dividing mesophase structure
Solution Approach 1:
The invention segments the internal structure by creating non-lamellar particles with complex three-dimensional architectures including cubic and hexagonal phases. This segmentation provides vastly increased internal surface area and creates multiple nanodomains that can independently solubilise different compounds, enhancing overall solubilisation capacity beyond what simple lamellar structures can achieve.
Solution Approach 2:
The formulation uses composite amphiphilic systems combining compounds with different spontaneous curvatures (positive and negative) to create complex non-lamellar mesophases. This composite approach enables the formation of tuneable interior structures with both polar and apolar nanodomains, providing enhanced solubilisation capacity for diverse compounds while maintaining structural stability.
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
Enables the formation of stable, colloidal non-lamellar particles with narrow size distributions, suitable for pharmaceutical and cosmetic applications, without the need for high energy methods, and maintains stability during storage, even with sensitive active agents.
Implementation Method 1
the amphiphile has both polar and apolar groups which cluster to form polar and apolar regions
Implementation Method 2
liquid crystalline phases such as the cubic P, cubic D, cubic G and hexagonal phases
Implementation Method 3
Depending upon their curvature, these phases may be described as normal (mean curvature towards the apolar region) or reversed (mean curvature towards the polar region)
Implementation Method 4
The non-lamellar liquid crystalline and L3 phases are thermodynamically stable systems
Implementation Method 5
dispersions of micrometer and sub-micrometer sized non-lamellar particles
Implementation Method 6
a bulk non-lamellar phase may be dispersed in a polar or non-polar solvent to form particles of a non-lamellar (especially liquid crystalline) phase in a bulk solvent
Data Source
AI summary
The present invention relates to compositions containing a) at least one monoacyl lipid; b) at least one diacyl glycerol and/or tochopherol; and c) at least one fragmentation agent; and optionally an active agent. The compositions are capable of self-dispersing to provide colloidal non-lamellar particles upon contact with an aqueous fluid. The invention additionally provides a method for forming non-lamellar particles from such compositions, and pharmaceutical formulations containing the compositions, plus non-lamellar particles formable from the compositions.