Stable Biologic Particles for Low-Volume Subcutaneous Delivery
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Solution Overview
Problem
Current biologic therapies, particularly monoclonal antibodies, face challenges in subcutaneous delivery due to the need for high concentrations and low volumes, which are difficult to achieve and can lead to patient discomfort and increased risk of infection. Additionally, formulating hyaluronan degrading agents into stable particles for delivery is challenging.
Innovation Solution
A stable particle composition comprising therapeutic biologics and hyaluronan degrading agents is developed, which includes particles with less than 25% internal void spaces and circularity between 0.80 and 1.00. These particles are suspended in a pharmaceutically acceptable liquid carrier and can be administered using a syringe or portable drug delivery device, eliminating the need for manual premixing or resuspension.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If high concentration therapeutic biologic particles are formulated for subcutaneous delivery, then delivery volume is reduced, but manufacturing stability and physical stability during processing and storage deteriorate
Solution Approach 1:
The therapeutic biologic is segmented into particulate form with controlled internal void spaces (less than 25%), creating discrete particles that can be suspended at high concentrations while maintaining stability during processing and storage
Solution Approach 2:
The particle composition uses a composite structure combining therapeutic biologic with stabilizing materials, creating a composite particle that maintains both high concentration capability and manufacturing/storage stability
2Quantity of substance
If hyaluronan degrading agents are formulated into particles, then bioavailability of therapeutic biologic is improved, but chemical and physical stability during processing and storage deteriorates
Solution Approach 1:
The hyaluronan degrading agent is pre-formulated into stable particles with controlled morphology (circularity 0.80-1.00) before administration, enabling the agent to remain stable during processing and storage while maintaining its bioavailability-enhancing function upon delivery
Solution Approach 2:
The particle parameters (internal void space less than 25%, circularity 0.80-1.00) are optimized to create a physical state that simultaneously protects the hyaluronan degrading agent's chemical stability and maintains its ability to enhance bioavailability
3Object-affected harmful factors
If high concentration particles are administered by subcutaneous injection, then patient discomfort and infection risk are reduced, but delivery volume constraints necessitate even higher concentrations that are difficult to obtain
Solution Approach 1:
The invention creates a copy or alternative delivery form (stable high-concentration particles) that bypasses the limitations of conventional liquid formulations, enabling achievement of the high concentrations needed for low-volume subcutaneous injection without the instability issues that previously made such concentrations unattainable
Data Source
AI summary
The present disclosure provides, in various embodiments, stable injectable particle suspensions of therapeutic biologics and hyaluronan degrading agents that permit administration without the need for resuspension. In particular, the compositions disclosed herein are highly concentrated, low-volume injectable particle suspensions that increase bioavailability of therapeutic biologics.