Spray-Dried Virus Powders Stabilized by MCTD Formulation
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Solution Overview
Problem
Existing methods for preparing inhalation products, such as spray drying, face challenges in stabilizing viruses during the process and storage, leading to instability and reduced viability of viruses in powder form, which is critical for effective vaccine delivery.
Innovation Solution
A method involving a mannitol-cyclodextrin-trehalose-dextran (MCTD) formulation is used for spray drying, which stabilizes viruses, maintaining their viability and stability during the process and storage, suitable for mass vaccinations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If spray drying is used to prepare viral powder formulations, then the process speed and cost-effectiveness are improved, but the virus stability and viability during drying and storage deteriorate
Solution Approach 1:
The patent introduces a stabilizing agent as an intermediary substance that mediates between the virus particles and the harsh drying conditions. The stabilizing agent forms a protective matrix around the virus particles during spray drying, preventing denaturation and aggregation, thereby enabling the virus to survive the rapid drying process while maintaining high viability in the final powder formulation
Solution Approach 2:
The patent optimizes multiple parameters including drying temperature, spray rate, and stabilizing agent concentration to achieve the desired balance between processing speed and virus stability. By carefully controlling these parameters, the process maintains high productivity while ensuring virus particles remain viable through the drying and storage phases
2Ease of manufacture
If spray drying is used to prepare viral powder formulations, then the cost-effectiveness is improved, but the virus stability during storage deteriorates
Solution Approach 1:
The stabilizing agent serves as a protective intermediary that enables long-term storage stability without requiring expensive cold chain infrastructure. This approach maintains virus viability during storage while keeping manufacturing costs low by eliminating the need for complex refrigeration systems and associated operational expenses
Solution Approach 2:
The patent modifies the formulation composition by incorporating specific stabilizing agents at optimized concentrations, which fundamentally changes the storage requirements from temperature-sensitive to ambient-stable conditions, thereby reducing storage costs while maintaining virus stability
3Ease of operation
If viruses are converted to powder form for delivery, then the aerosolization characteristics are improved, but the viral activity retention deteriorates
Solution Approach 1:
The stabilizing agent acts as a protective intermediary that forms a protective matrix around the virus particles during aerosolization. This matrix prevents mechanical stress and environmental damage during inhalation delivery, maintaining high viral activity retention while enabling effective aerosol formation and lung deposition
Solution Approach 2:
The patent creates a composite powder formulation consisting of virus particles embedded in a stabilizing agent matrix. This composite structure provides both the aerosolization benefits of powder form and the protective advantages of the stabilizing agent, achieving synergistic effects that maintain viral activity while enabling inhalation delivery
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 MCTD formulation results in a stable, spray-dried virus powder with improved aerosolization characteristics and resistance to moisture, ensuring high viral activity retention and extended storage stability, making it suitable for inhalation and other delivery routes.
Implementation Method 1
The glass transition temperature (Tg) of MCTD powder sample
Implementation Method 2
Spray drying, whereby a liquid is transformed into dry powder particles by nebulization of droplets in hot drying air
Implementation Method 3
Spray drying, whereby a liquid is transformed into dry powder particles by nebulization of droplets in hot drying air
Implementation Method 4
improved aerosolization characteristics and resistance to moisture
Data Source
AI summary
Viruses, and particularly genetically engineered, replication deficient viruses such as adenoviruses, poxviruses, MVA viruses, and baculoviruses which encode one or more antigens of interest, such as TB, malarial, and HIV antigens, are spray dried with a mannitol-cyclodextrin-trehalose-dextran (MCTD) to form a powder where the viability of the viruses are maintained at a suitable level for mass vaccinations after spray drying, and where the viability of the viruses are maintained at suitable level over a period of storage time, even in the presence of humidity.