Antibody Solid Dosage Wet Granulation for Stable GI Release
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Solution Overview
Problem
Existing methods for preparing solid dosage forms of antibodies and functional fragments thereof, such as extrusion-spheronization, are unsuitable due to high temperatures and shear forces that cause instability and loss of biological activity, and there is a need for a method that preserves stability and activity during preparation and ensures optimal release over a short or prolonged period.
Innovation Solution
A method involving wet granulation, extrusion, and spheronization with the inclusion of a surfactant in the binding liquid to improve recovery and stability of antibodies or functional fragments, using specific excipients and buffers to minimize interactions and maintain activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If extrusion-spheronization method is used to prepare solid dosage forms, then manufacturing efficiency and particle quality are improved, but high temperatures and shear forces cause instability and loss of biological activity of antibodies
Solution Approach 1:
The patent changes the temperature parameter from high (conventional extrusion-spheronization) to low (below 55°C, preferably below 40°C) to preserve antibody stability while maintaining manufacturing efficiency through optimized wet granulation and extrusion processes
Solution Approach 2:
The patent introduces a surfactant as an intermediary substance in the binding liquid during wet granulation to reduce surface tension and minimize shear stress on antibodies, thereby protecting biological activity while enabling effective granulation
2Productivity
If high shear forces are applied during extrusion and spheronization, then particle formation and manufacturing efficiency are improved, but physical instability such as denaturation and aggregation of antibodies occurs
Solution Approach 1:
The patent optimizes extrusion parameters including temperature (below 55°C), pressure, and screw speed to reduce shear forces while maintaining effective particle formation and manufacturing efficiency
Solution Approach 2:
The patent uses a composite binding liquid comprising surfactant, buffer, and excipients that work synergistically to protect antibodies from shear-induced denaturation and aggregation while enabling effective extrusion and spheronization
3Ease of manufacture
If conventional processing methods are used, then manufacturing simplicity is maintained, but chemical instability such as fragmentation, oxidation, and deamination of antibodies occurs
Solution Approach 1:
The patent introduces a buffer system as an intermediary to maintain optimal pH conditions throughout processing, preventing chemical instability including fragmentation, oxidation, and deamination of antibodies while maintaining manufacturing simplicity
Solution Approach 2:
The patent creates a protected processing environment using antioxidants and inert atmospheric conditions to prevent oxidation and other chemical degradation of antibodies during manufacturing
Data Source
Figure 1(A)~1(C)
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AI summary
The present invention relates to a method for preparing immediate and sustained release solid dosage forms, comprising antibodies and functional fragments thereof, by wet granulation, extrusion and spheronization,optionally coated with a delayed release coating the solid dosage forms prepared by the method and the use of the solid dosage forms in the topical treatment in the gastrointestinal tract of a patient.