Antibody Solid Dosage Forms via Low-Temperature Spheronization
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Solution Overview
Problem
Existing methods for preparing solid dosage forms using extrusion-spheronization are unsuitable for large biologically active polypeptides like antibodies and functional fragments thereof due to high temperatures, shear forces, and excipient interactions, leading to stability and activity loss, and inadequate release profiles for gastrointestinal treatment.
Innovation Solution
A method involving wet granulation, extrusion, and spheronization using specific excipients such as microcrystalline cellulose, surfactants, buffers, and disintegrants, with controlled temperatures below 55°C, to prepare stable and active solid dosage forms, including immediate and sustained release formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional extrusion-spheronization methods are used to prepare solid dosage forms, then manufacturing efficiency and particle formation are improved, but antibody stability and activity are lost due to high temperatures and shear forces
Solution Approach 1:
The patent changes the temperature parameter from conventional high temperatures to below 55°C throughout the extrusion-spheronization process, and adjusts shear force parameters by modifying extrusion speed and spheronization conditions. This resolves the contradiction by maintaining manufacturing efficiency while preserving antibody stability through optimized process parameters.
Solution Approach 2:
The patent introduces specific excipients as intermediaries that protect antibodies during processing. These excipients form a protective matrix around the antibodies during wet granulation, extrusion, and spheronization, reducing direct exposure to shear forces and temperature stress while allowing the process to proceed efficiently.
2Shape
If high shear forces are applied during extrusion and spheronization, then particle formation and spherical shape are improved, but antibody activity and integrity deteriorate
Solution Approach 1:
The patent optimizes shear force parameters by controlling extrusion speed, spheronization rotation speed, and feed rate to maintain gentle yet effective particle formation. This resolves the contradiction by achieving adequate sphericity while minimizing antibody damage through parameter optimization.
Solution Approach 2:
The patent applies beforehand cushioning by incorporating protective excipients and optimizing the binder composition before the extrusion-spheronization process begins. This protective matrix cushions the antibodies against shear forces during particle formation, maintaining both shape and antibody integrity.
3Productivity
If high temperatures are used during processing, then drying efficiency and particle formation are improved, but antibody denaturation and aggregation occur
Solution Approach 1:
The patent changes the temperature parameter to maintain processing temperature below 55°C throughout all stages including drying. This resolves the contradiction by achieving adequate drying efficiency through extended processing time at lower temperatures, thereby preventing antibody denaturation and aggregation.
Solution Approach 2:
The patent employs continuous low-temperature processing throughout wet granulation, extrusion, spheronization, and drying stages. This continuous gentle processing maintains antibody stability while achieving particle formation and drying through sustained action rather than high-temperature short-duration processing.
4Ease of manufacture
If conventional excipients are used in solid dosage forms, then manufacturing ease and cost are improved, but antibody recovery and release profiles are inadequate
Solution Approach 1:
The patent uses composite excipient formulations including specific binders, fillers, and protective agents that work synergistically. This composite approach maintains manufacturing ease while improving antibody recovery and release profiles through the combined properties of multiple excipients that protect and facilitate antibody delivery.
Solution Approach 2:
The patent introduces specific excipients as intermediaries that facilitate antibody recovery. These excipients form a protective and release-friendly matrix that maintains manufacturing simplicity while enabling high antibody recovery and appropriate release profiles through their mediating protective and release functions.
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
Preserves the stability and activity of antibodies or functional fragments during preparation, ensures optimal recovery, and allows controlled release over time, suitable for gastrointestinal treatment.
Implementation Method 1
wet granulating by adding a binding liquid to the powder blend
Implementation Method 2
extruding the wet mass with a screw extruder
Implementation Method 3
spheronizing the extrudate in a rotating drum
Implementation Method 4
drying the wet spheroids in a vacuum dryer
Data Source
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.