Lyophilized Nucleic Acid Formulations With Faster, More Uniform Drying
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Solution Overview
Problem
Pharmaceutical compositions containing nucleic acids, such as mRNA vaccines, are unstable and require ultracold storage, which is costly and difficult to maintain, especially in resource-poor regions, and lyophilization processes for these compositions result in vial-to-vial inconsistencies and loss of critical quality attributes like encapsulation efficiency.
Innovation Solution
Increasing the surface area to volume ratio of the pharmaceutical composition before or during freeze-drying leads to faster sublimation and desorption, enabling improved payload encapsulation efficiency and homogeneity, allowing for continuous manufacturing and reducing environmental impact.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional lyophilization is used for nucleic acid containing pharmaceuticals, then the process is time-consuming and results in high inherent heterogeneity, but increasing surface area to volume ratio enables faster sublimation and improved homogeneity
Solution Approach 1:
The invention divides the pharmaceutical composition into multiple smaller vials or containers instead of using fewer larger vials. This segmentation increases the total surface area to volume ratio, enabling faster and more uniform sublimation of ice crystals throughout the lyophilization process, thereby improving both productivity and manufacturing precision simultaneously
Solution Approach 2:
The invention transitions from traditional batch lyophilization to a continuous lyophilization process where vials are processed sequentially through a conveyor system. This dimensional change from batch to continuous processing enables better control over sublimation conditions and improves homogeneity while increasing productivity
2Ease of manufacture
If conventional batch freeze-drying is used, then the process is simple to implement, but it causes loss of critical quality attributes like encapsulation efficiency and payload integrity
Solution Approach 1:
The invention modifies critical lyophilization parameters including temperature profiles, pressure conditions, and agitation rates to optimize the sublimation process. These parameter changes enable faster drying while preserving the encapsulation efficiency and payload integrity of the nucleic acid-containing lipid carrier particles
Solution Approach 2:
The invention implements continuous lyophilization where the pharmaceutical composition undergoes uninterrupted sublimation and drying processes. This continuous action prevents the formation of large ice crystals that cause mechanical stress and maintains encapsulation efficiency, while also eliminating the need for repeated freezing-thawing cycles
3Stability of the object's composition
If ultracold storage is maintained to preserve nucleic acid stability, then product quality is preserved, but cost and distribution complexity increase significantly
Solution Approach 1:
The invention performs lyophilization as a preliminary action before distribution, transforming the nucleic acid-containing formulation into a stable dried powder form. This preliminary processing eliminates the need for continuous ultracold storage during distribution and storage, significantly reducing cold chain complexity while maintaining product stability through proper lyophilization formulation
Solution Approach 2:
The invention replaces the mechanical ultracold storage system with a chemical stabilization approach through lyophilization formulation. By optimizing the composition and drying conditions, the product achieves stability without requiring continuous refrigeration, substituting a complex mechanical cooling system with a chemically stable dried formulation
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 method results in a lyophilized product with greater than 75% encapsulation efficiency, reduced vial-to-vial inconsistencies, and improved production homogeneity, suitable for continuous manufacturing and stable storage at room temperature.
Implementation Method 1
the sublimation phase
Implementation Method 2
the desorption step
Implementation Method 3
the freezing step
Data Source
AI summary
The present invention provides lyophilised pharmaceutical compositions and methods of making said lyophilised pharmaceutical compositions. More particularly, the present invention provides lyophilised pharmaceutical compositions comprising nucleic acid and lipid carrier particles and methods of making said lyophilised pharmaceutical compositions. The provided lyophilised compositions have improved critical quality attributes (CQAs) and the provided methods prevent the need for a deep-freeze cold chain. The present invention further provides the use of said lyophilised pharmaceutical compositions in medicine.