Cryogranulation Dispenser Assembly for Anti-Clog Pellet Formation
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Solution Overview
Problem
Existing cryogranulation systems are not suitable for manufacturing pharmaceutical formulations, leading to issues such as agglomeration, increased lyophilization times, lack of pellet formation, and clogging due to streaming and freezing of pharmaceutical solutions or suspensions, resulting in inefficient pelletization and product loss.
Innovation Solution
A cryogranulation system with an improved dispenser assembly that includes a housing and dispenser subassembly for uniform dispensing of pharmaceutical compositions into a cooling agent, producing pellets of a predetermined size range, and a transport system for separating and transporting the pellets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If commercial cryogranulation systems are used for pharmaceutical formulations, then frozen pellets can be produced, but agglomeration occurs and pellet size uniformity is poor
Solution Approach 1:
The pharmaceutical composition is segmented into multiple fine dispense streams through a multi-orifice dispenser assembly, creating numerous small droplets that freeze into uniform pellets rather than large agglomerates. The dispenser assembly divides the bulk material flow into controlled individual streams.
Solution Approach 2:
A controlled atmosphere environment serves as an intermediary medium between the pharmaceutical composition and cooling agent, preventing premature freezing and agglomeration while allowing uniform pellet formation. The controlled atmosphere mediates the phase transition process.
2Productivity
If pharmaceutical solutions are dispensed in existing systems, then pelletization occurs, but streaming and freezing cause clogging and product loss
Solution Approach 1:
The physical parameters of the pharmaceutical composition are modified by adjusting temperature, viscosity, and flow rate within specific ranges to prevent freezing during dispensing. The system maintains parameters within thresholds that avoid clogging while enabling subsequent pelletization.
Solution Approach 2:
The pharmaceutical composition undergoes preliminary conditioning and heating before dispensing to maintain it in a flowable state, preventing premature freezing and clogging. The system prepares the material in advance to ensure smooth delivery through the dispenser.
3Quantity of substance
If conventional dispensing methods are used, then material can be delivered, but uniform distribution over the cooling agent is not achieved
Solution Approach 1:
The dispenser assembly segments the material flow into multiple parallel streams that spread uniformly across the cooling agent surface. This segmentation achieves both high delivery rate and uniform distribution simultaneously.
Solution Approach 2:
The system transitions from single-point dispensing to multi-dimensional distribution by arranging multiple dispensing orifices in a pattern that spreads material across the cooling agent surface area, achieving uniform coverage.
4Productivity
If existing cryogranulation equipment is used, then frozen product can be produced, but pellet fines are increased and yield is reduced
Solution Approach 1:
By precisely controlling dispensing parameters (flow rate, temperature, pressure) within optimal ranges, the system produces pellets within the desired size specification and minimizes fines, thereby increasing overall yield.
Solution Approach 2:
The system replaces mechanical grinding or size-reduction methods with a controlled freezing process that directly forms pellets of the desired size, eliminating the need for post-processing that generates fines and reduces yield.
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 system achieves more homogeneous pellet sizes, improving process efficiency and drug product yield by minimizing pellet fines and eliminating dispenser freezing issues, suitable for pharmaceutical substances like proteins and peptides adsorbed onto carrier particles.
Implementation Method 1
A material to be cryogranulated is introduced into the flow of liquid nitrogen from a dispenser positioned above the tray. The material is frozen by the liquid nitrogen into pellets or granules.
Implementation Method 2
The material is frozen by the liquid nitrogen into pellets or granules
Implementation Method 3
The pharmaceutical composition into the cooling agent, the dispenser assembly including a housing and a dispenser subassembly... producing pellets of the pharmaceutical composition
Data Source
AI summary
Cryogranulation systems with improved dispenser assemblies are provided for use in manufacturing frozen pellets of pharmaceutical substances in a fluid medium. Methods of cryogranulating the pharmaceutical substance in the fluid medium are also provided. In particular embodiments, the dispenser assembly is used with suspensions or slurries of pharmaceutical compositions including biodegradable substances, such as proteins, peptides, and nucleic acids. In certain embodiments, the pharmaceutical substance can be adsorbed to any pharmaceutically acceptable carrier particles suitable for making pharmaceutical powders. In one embodiment, the pharmaceutical carrier can be, for example, diketopiperazine-based microparticles. The dispenser assembly improves the physical characteristics of the cryopellets formed and minimizes product loss during processing.