Electrosprayed Therapeutic Particles for High-Concentration Stability
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Solution Overview
Problem
Existing therapeutic and diagnostic formulations, particularly those containing monoclonal antibodies, face challenges in achieving high concentrations with stability and reduced aggregation, fragmentation, and charge variants, which are unattainable in aqueous solutions, leading to issues with viscosity and degradation.
Innovation Solution
The method involves electrospraying a stream of a therapeutic or diagnostic agent into a collector to form particles with controlled concentrations and viscosities, using encapsulants like poly(vinyl alcohol) and organic solvents, resulting in formulations with less than 10% aggregation, fragmentation, and charge variant changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high concentrations of therapeutic or diagnostic agents are formulated in aqueous solution, then the dose delivery efficiency is improved, but the fluid dynamic viscosity increases and degradation is accelerated
Solution Approach 1:
The patent changes the physical state of the formulation from aqueous solution to non-aqueous suspension, and transforms the therapeutic agent from dissolved state to encapsulated particulate form. This parameter change enables high concentrations (10-1000 mg/mL) while maintaining low viscosity and high stability, as the particles remain suspended rather than dissolved, preventing the viscosity increase and degradation pathways associated with concentrated aqueous solutions
Solution Approach 2:
The patent utilizes phase transition by forming solid or semi-solid particles from the therapeutic agent and suspending them in a non-aqueous carrier. This phase separation allows the therapeutic to be delivered in a stable suspended state rather than a dissolved state, enabling high concentration formulations with minimal viscosity and enhanced stability against degradation
2Quantity of substance
If high concentrations of therapeutic or diagnostic agents are formulated in aqueous solution, then the volume of formulation is reduced, but aggregation and fragmentation increase
Solution Approach 1:
The patent segments the therapeutic agent into discrete encapsulated particles, each containing the therapeutic in a protected form. This segmentation prevents intermolecular aggregation that occurs in concentrated aqueous solutions, as each particle acts as an independent unit. The encapsulation structure maintains agent integrity while enabling high concentration formulations through suspended particulate matter
Solution Approach 2:
The patent introduces an encapsulant material as an intermediary between the therapeutic agent and the aqueous environment. This encapsulant shell protects the therapeutic from aggregation and fragmentation pathways, allowing high concentrations to be maintained with preserved agent integrity. The non-aqueous carrier suspension medium also serves as an intermediary that prevents direct therapeutic-therapeutic interactions that lead to aggregation
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 method produces stable particles with high agent concentrations, enabling efficient administration with minimal volume and reduced patient discomfort, suitable for various administration routes.
Implementation Method 1
forming particles by electrospraying, e.g., conventional electrospraying, a stream of a first liquid including a first therapeutic or diagnostic agent toward a collector
Implementation Method 2
electrospraying a first liquid including a first therapeutic or diagnostic agent to form droplets and removing (e.g., evaporating) the first liquid to produce particles from the droplets
Data Source
AI summary
The invention provides particles, compositions including the particles, and methods of making the particles using electrospray. In certain embodiments, the particles allow for high concentrations of a therapeutic or diagnostic agent to be delivered at low viscosity. Particles may also exhibit beneficial properties with respect to stability.