PVA Stabilized PEG Particles for Lyophilization
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Solution Overview
Problem
PEG-coated particles used in drug delivery face challenges with physical and chemical instability during lyophilization and freezing, leading to particle aggregation and size changes, which affect their efficacy and stability, particularly when reconstituted, and require stabilization to maintain their intended size and function for intravenous administration.
Innovation Solution
The method involves adding polyvinyl alcohol (PVA) to an aqueous composition of PEG-coated particles before lyophilization or freezing, along with optional sucrose, to prevent particle aggregation and size increase, ensuring the particles maintain their original size and stability upon reconstitution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PEG chains are used to coat particles for steric stabilization and prolonged circulation, then particle stability in biological systems is improved, but particle aggregation occurs during freeze-drying and freezing processes
Solution Approach 1:
Sucrose acts as an intermediary substance that mediates between the PEG-coated particles and the freeze-drying process. The sucrose forms a protective matrix around the particles during freezing, preventing PEG chain entanglement and aggregation, and maintains particle dispersion and size stability throughout the lyophilization process.
Solution Approach 2:
The invention changes the physical and chemical parameters of the formulation by adding sucrose, which alters the freezing point, glass transition temperature, and molecular mobility during freeze-drying. These parameter changes prevent PEG chain crystallization and entanglement, maintaining particle stability while preserving the beneficial steric stabilization properties of PEG.
2Reliability
If particles are stored as dry powder through lyophilization, then microbial contamination is prevented and handling is improved, but particle aggregation and size increase occur upon reconstitution
Solution Approach 1:
Sucrose is added to the particle formulation before lyophilization to perform preliminary protective action. The sucrose forms a protective environment around the particles during the freeze-drying process, preventing aggregation and size changes that would otherwise occur upon reconstitution, thereby preserving manufacturing precision through the storage and reconstitution cycle.
3Reliability
If PEG chains are present in the formulation, then steric stabilization and reduced macrophage uptake are achieved, but PEG chain entanglement and crystallization occur during freeze-drying
Solution Approach 1:
Sucrose serves as an intermediary that separates and isolates the PEG chains during the freeze-drying process. The sucrose matrix prevents direct contact and entanglement of PEG chains, eliminating the harmful crystallization and aggregation effects while preserving the PEG's steric stabilization properties for prolonged circulation.
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 effectively stabilizes PEG-coated particles during lyophilization and freezing, preventing aggregation and size changes, thus maintaining their intended size and stability, enhancing their circulation time and therapeutic efficacy by ensuring consistent drug delivery.
Implementation Method 1
The flexible and hydrophilic PEG chains apparently provide a steric stabilization that reduces protein interaction and uptake by macrophages
Implementation Method 2
adding polyvinyl alcohol (PVA) to an aqueous composition comprising the particles
Implementation Method 3
A commonly used process that converts solutions or suspensions into solids is freeze-drying or lyophilization. It involves removing water from a frozen sample by sublimation and desorption under vacuum
Implementation Method 4
adding polyvinyl alcohol (PVA) to an aqueous composition of PEG-coated particles before lyophilization or freezing
Data Source
AI summary
Provided herein are use of polymeric excipients, specifically polyvinyl alcohols, optionally in conjunction with sugars, as cryoprotectants to prevent aggregation of PEG-containing particles. Also provided are PEG-containing particles comprising such polymeric excipients.