Lipid Microsphere Depot Composition for Initial Burst Control
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Solution Overview
Problem
Existing depot preparations face challenges in controlling the initial burst of drug release, leading to side effects and reduced efficacy, and have issues with microsphere suspensibility and agglomeration, particularly when using GLP-1 agonists like liraglutide and semaglutide.
Innovation Solution
A depot composition is developed with microspheres containing an oil layer comprising a lipid component and a biodegradable polymer, prepared through methods such as O/W or W/O/W emulsions to control initial burst and enhance suspensibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If lipids are used as release control substance in microspheres, then initial burst is suppressed, but microsphere properties deteriorate due to strong hydrophobic properties
Solution Approach 1:
The patent uses a composite lipid system combining hydrophobic lipids (for initial burst control) with hydrophilic lipids (for microsphere stability). This composite approach allows the hydrophobic lipids to effectively suppress initial drug release while the hydrophilic lipids counteract the deteriorating effects of strong hydrophobicity, maintaining microsphere integrity and performance.
2Reliability
If microspheres are stored in freeze-dried state and suspended in water for injection, then storage safety is improved, but suspension properties deteriorate leading to agglomeration and sedimentation
Solution Approach 1:
The patent incorporates hydrophilic lipids in the microsphere composition that improve wetting and suspension properties. These hydrophilic components prevent agglomeration and sedimentation when microspheres are reconstituted from freeze-dried state, ensuring uniform suspension without compromising storage stability.
3Duration of action of stationary object
If PLGA polymer is modified to form microspheres, then sustained release is achieved, but drug approval becomes difficult
Solution Approach 1:
The patent modifies the chemical composition parameters of the lipid system while maintaining the sustained-release functionality. By using specific ratios of hydrophobic to hydrophilic lipids and selecting particular lipid types, the formulation achieves sustained release without requiring complex PLGA modifications, thereby facilitating regulatory approval.
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 composition effectively suppresses excessive initial drug release, ensuring uniform and continuous drug delivery, with improved suspensibility and stability, reducing side effects and enhancing therapeutic efficacy.
Implementation Method 1
lipids have disadvantages of failing to show a sufficient effect in suppressing the initial burst and causing the properties of the microspheres to deteriorate due to their strong hydrophobic properties
Implementation Method 2
microspheres including an oil layer (O layer) including a lipid component and a biodegradable polymer
Implementation Method 3
preparing an O/W emulsion or a W1/O/W2 emulsion by inputting the oil phase solution or W1/O emulsion into a second water phase 2 (W2) solution
Data Source
AI summary
The present invention relates to a depot composition comprising a lipid component inside microspheres. The depot composition is capable of controlling the excessive initial burst of an active ingredient from a formulation containing a biodegradable polymer and an active ingredient and has excellent suspensibility, and thus, even when using same as an injection, a layperson can obtain the effect of the active ingredient uniformly and continuously.