Lipid Pre-Concentrate Liquid Crystal Phase Transition for Sustained Release
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Solution Overview
Problem
Conventional sustained release formulations using PLGA induce inflammation and have low biodegradability, leading to prolonged presence of drug delivery particles in the body, causing discomfort and reduced patient compliance.
Innovation Solution
A lipid pre-concentrate comprising sorbitan unsaturated fatty acid ester with multiple hydroxyl groups, phospholipids, and a liquid crystal hardener forms a liquid crystal phase upon exposure to aqueous fluids, enhancing drug release and biodegradability, thus providing a safe and effective sustained release mechanism.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If PLGA solid particles are used for sustained release, then the effective plasma concentration can be maintained for a specific period, but inflammation and pain occur at the injection site due to degradation products
Solution Approach 1:
The invention changes the material parameters from PLGA polymer to specific lipid components (sorbitan unsaturated fatty acid ester, phospholipid, and liquid crystal hardener), fundamentally altering the degradation pathway from acidic monomers to biocompatible lipid metabolism products, thereby eliminating inflammation while maintaining sustained release capability
Solution Approach 2:
The invention uses a composite lipid system comprising three specific components (sorbitan unsaturated fatty acid ester, phospholipid, and liquid crystal hardener) that work synergistically to form liquid crystal structures, providing both sustained release functionality and biocompatibility, avoiding the harmful effects of single-material PLGA degradation
2Duration of action of stationary object
If PLGA solid particles of 10-100 micrometers are injected for sustained release, then drug release is achieved over several months, but patient compliance decreases due to pain and inflammation
Solution Approach 1:
The invention changes the physical state parameter from solid particles to liquid crystal phase, allowing the formulation to be injected in liquid form and then transition to gel-like structure in vivo, eliminating injection pain while maintaining prolonged drug release through the liquid crystal-to-gel transition mechanism
Solution Approach 2:
The invention converts the potential harm of solid particle injection (pain and inflammation) into benefit by using liquid crystal hardeners that enable phase transition from liquid (injectable) to gel (sustained release matrix), turning what would be a harmful solid particle injection into a beneficial painless liquid injection with controlled gel formation
3Ease of manufacture
If conventional organic solvents are used in pre-formulations, then low viscosity and ease of injection are achieved, but drug activity decreases and safety concerns arise
Solution Approach 1:
The invention changes the solvent system from conventional organic solvents to a water-based liquid crystal system, eliminating solvent-induced drug deactivation while maintaining low viscosity through the liquid crystal phase and ensuring safety through biocompatible lipid components that metabolize naturally in the body
Solution Approach 2:
The liquid crystal hardener acts as an intermediary component that enables the formulation to exist as a low-viscosity liquid during preparation and injection, then transitions to a gel-like structure in vivo, mediating between the requirements for ease of administration and drug stability/safety without requiring harmful organic solvents
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 lipid pre-concentrate ensures prolonged drug release without pain or inflammation, improving patient compliance and biodegradability, maintaining effective plasma concentrations for extended periods while minimizing side effects.
Implementation Method 1
a lipid pre-concentrate comprising a) a sorbitan unsaturated fatty acid ester having a polar head with at least two or more -OH (hydroxyl) groups; b) a phospholipid; and c) a liquid crystal hardener... exists as a liquid state in the absence of aqueous fluid and transits into a gel-like liquid crystal upon exposure to aqueous fluid
Data Source
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AI summary
Disclosed is a sustained release lipid pre-concentrate, comprising: a) a sorbitan unsaturated fatty acid ester having a polar head with at least two or more -OH (hydroxyl) groups; b) a phospholipid; and c) a liquid crystal hardener, free of an ionizable group, having a hydrophobic moiety of 15 to 40 carbon atoms with a triacyl group or a carbon ring structure. The lipid pre-concentrate exists as a liquid phase in the absence of aqueous fluid and forms into a liquid crystal in the presence of aqueous fluid. Also, a pharmaceutical composition further comprising a pharmacologically active ingredient plus the pre-concentrate is provided.