Antibody Pulmonary Delivery via Acidic Buffer Formulation
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Solution Overview
Problem
The pulmonary delivery of antibodies is challenging due to issues such as intermolecular interactions and physico-chemical degradation, leading to aggregation and loss of biological activity, especially during aerosolization and nebulization.
Innovation Solution
A formulation comprising an antibody or antibody derivative, a buffering agent like acetate or histidine, and an aqueous medium with a pH of 3.5 to 5.5, along with a surfactant like polysorbate 80, is used to create an aerosol with droplets of 0.5 to 5 μm diameter, which is nebulized using a mesh nebulizer for stable delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If antibodies are administered via pulmonary route, then non-invasive delivery is achieved, but protein stability and biological activity are compromised due to aerosolization stress
Solution Approach 1:
The patent applies parameter changes by optimizing formulation pH to acidic ranges (pH 3.0-5.5, preferably pH 3.5-4.5) and controlling buffer composition (using acetate or histidine buffers) to maintain antibody stability during aerosolization. These parameter adjustments prevent aggregation and degradation while enabling pulmonary delivery
Solution Approach 2:
The patent uses buffering agents (acetate, histidine) and surfactants as intermediary substances that mediate between the antibody and the harsh aerosolization environment. These intermediaries protect the antibody from shear stress and interfacial degradation, enabling stable pulmonary delivery
2Ease of operation
If antibodies are formulated for aerosolization, then pulmonary delivery is enabled, but aggregation occurs due to intermolecular interactions
Solution Approach 1:
The patent changes formulation parameters by using acidic pH (3.0-5.5) and specific buffer systems to alter the electrostatic interactions between antibody molecules. This prevents intermolecular aggregation while maintaining solubility and stability during nebulization
Solution Approach 2:
The patent introduces surfactants and buffering agents as intermediary substances that interfere with antibody-antibody interactions. These intermediaries adsorb at interfaces and in solution, preventing aggregation during aerosolization and pulmonary delivery
3Productivity
If antibodies undergo nebulization, then aerosol droplets are formed, but physico-chemical degradation occurs due to shear stress and temperature increase
Solution Approach 1:
The patent applies beforehand cushioning by incorporating stabilizing excipients (buffers, surfactants) into the formulation before nebulization. These protective agents are pre-loaded to cushion the antibody against upcoming shear stress and thermal stress during aerosol generation
Solution Approach 2:
The patent optimizes formulation parameters including pH (3.0-5.5), buffer concentration, and surfactant content to create a formulation that is resistant to nebulization stress. These parameter changes enable high productivity aerosol generation while preserving biological activity
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 maintains the stability and biological activity of antibodies upon nebulization, reducing aggregation and ensuring effective pulmonary delivery for treating lung diseases.
Implementation Method 1
a buffering agent selected from the group consisting of acetate, histidine and combinations thereof
Implementation Method 2
mesh nebulizer
Data Source
AI summary
The present invention relates to the pulmonary delivery of antibodies or antibody derivatives.