Microwave Vacuum Drying of Frozen Biological Pellets

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Solution Overview

Problem

Existing methods for preparing dried biological materials, such as lyophilization, face challenges in achieving fast reconstitution times and efficient drying processes, particularly for spherical pellets, due to complex assembly designs, leakage, and prolonged drying times.

Innovation Solution

A method involving dispensing liquid droplets onto a solid surface, freezing them without cryogenic contact, and then using microwave vacuum drying to produce dried, spherical pellets with rapid sublimation times, achieving less than 12 hours of drying time and optimal reconstitution within minutes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional lyophilization is used to prepare dried biological materials, then long-term storage stability is achieved, but reconstitution time is prolonged and drying process takes excessive time

Engineering Contradiction:
Improvestorage stabilityVSAvoidreconstitution time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention changes the physical state parameters of water in the biological material by using microwave irradiation to heat and evaporate water, transitioning from the slow sublimation process of traditional lyophilization to rapid microwave-assisted drying. This parameter change enables faster reconstitution while maintaining storage stability through proper formulation and controlled drying conditions

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the mechanical vacuum-based sublimation system with an electromagnetic microwave heating system. This substitution eliminates the need for complex vacuum chambers and long drying cycles, achieving rapid water removal and enabling fast reconstitution times while preserving product stability through controlled energy input

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If microwave vacuum drying is applied to frozen pellets, then drying time is reduced to less than 12 hours, but temperature control must be maintained below 45°C to preserve biological material integrity

Engineering Contradiction:
Improvedrying speedVSAvoidmaximum temperature
Core Design Contradiction:
ProductivityVSTemperature

Solution Approach 1:

The invention uses periodic microwave irradiation cycles with controlled power levels to gradually remove water from the frozen pellets. By applying microwave energy in controlled intervals and adjusting power levels, the process achieves rapid drying while maintaining temperature below 45°C, preserving biological material integrity through repeated heating and cooling cycles

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The invention introduces vacuum conditions as an intermediary environment that lowers the boiling point of water, enabling microwave drying to proceed at lower temperatures. The vacuum atmosphere facilitates rapid water evaporation at reduced temperatures, allowing the biological material to be dried quickly without thermal degradation

Inventive Principle:
Principle #24Intermediary (Mediator)

3Shape

If liquid droplets are dispensed onto a solid surface for freezing, then spherical pellet formation is achieved, but complex assembly designs and leakage issues occur with traditional methods

Engineering Contradiction:
Improvespherical pellet shapeVSAvoidassembly design complexity
Core Design Contradiction:
ShapeVSDevice complexity

Solution Approach 1:

The invention uses a simple flat solid surface that allows liquid droplets to freeze into spherical pellets through self-directed freezing. The droplets naturally form spheres as they freeze on the cold surface without requiring complex molds, cavities, or assembly mechanisms. This self-service approach eliminates leakage issues and simplifies the device design while maintaining consistent spherical pellet formation

Inventive Principle:
Principle #25Self-service

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 method results in dried pellets with faster reconstitution times and improved stability, reducing the complexity and time associated with traditional lyophilization processes while maintaining the integrity of biological materials.

Implementation Method 1

applying microwave radiation in a traveling wave format at a power in a range of between 0.5 and 8 KW/hr/Kg to the frozen pellet under a pressure below atmospheric pressure

Methodology Applied
Scientific EffectMicrowave radiation: Microwave Radiation

Implementation Method 2

the ice in the frozen sample directly changes to water vapor or sublimes

Methodology Applied
Scientific EffectSublimation: Sublimation

Implementation Method 3

water is desorbed from the remaining non-ice phase of the sample

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 4

dispensing an aliquot of a liquid composition comprising the virus as a single droplet onto a solid surface, wherein the temperature of the surface is at -90°C or below

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Data Source

PatentEP3057978B1Method of microwave vacuum drying spherical-shaped pellets of biological materials
Publication Date: 2022.09.14 MERCK SHARP & DOHME LLC

AI summary

Methods for preparing dried pellets of biological materials are described. The pellets can have a substantially spherical shape and are prepared by freezing droplets of a liquid composition of a desired biological material on a solid surface followed by microwave vacuum drying the frozen droplets. These methods are useful for preparing dried pellets having a high concentration of a desired biological material, in particular a therapeutic protein or vaccine, and which have a faster reconstitution time than lyophilized powder cakes prepared in vials.