Continuous Spray Drying via Microfluidization
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Solution Overview
Problem
Current spray drying processes for pharmaceuticals face challenges with low solubility and stability of active pharmaceutical ingredients and excipients, leading to inefficient dissolution kinetics, limited batch sizes due to feed tank capacity, and instability issues caused by hold times during batch preparation.
Innovation Solution
A continuous spray drying process that uses microfluidization to micronize and homogenize a suspension of active pharmaceutical ingredients and excipients within a micro-reactor or micro-channel, eliminating the need for additional batch operations and reducing hold times, thereby enhancing solubility and dissolution kinetics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If batch mode spray solution preparation is used in a stirred tank, then the process is simple to operate, but the dissolution kinetics are slow and the process requires long hold times leading to instability
Solution Approach 1:
The patent replaces the conventional stirred tank mechanical mixing system with a microfluidization system that uses high-pressure fluid dynamics and micro-channel flow patterns to achieve rapid dissolution. The microfluidizer forces the suspension through micro-channels at high pressure, creating intense mixing and shear forces that dramatically accelerate dissolution kinetics compared to traditional mechanical stirring.
Solution Approach 2:
The patent changes key process parameters by transitioning from batch mode to continuous mode operation, and from atmospheric pressure to high-pressure microfluidization. These parameter changes enable rapid dissolution while maintaining operational simplicity through continuous automated processing.
2Quantity of substance
If the feed tank capacity is increased to handle low solubility APIs, then larger batches can be prepared, but the hold time increases causing chemical degradation
Solution Approach 1:
The patent implements continuous spray solution preparation and feeding, eliminating the batch hold time period where the spray solution sits in the feed tank. The continuous operation ensures that the spray solution is prepared and immediately processed through spray drying, preventing chemical degradation while maintaining the ability to handle large quantities of low solubility APIs.
3Productivity
If particle size is reduced by milling to improve dissolution kinetics, then dissolution rate increases, but additional discontinuous processing steps are required
Solution Approach 1:
The patent merges the particle size reduction function with the spray solution preparation function into a single integrated microfluidization step. The microfluidizer simultaneously micronizes the API particles and dissolves them in the solvent, eliminating the need for separate milling and dissolution steps while achieving both particle size reduction and complete dissolution.
Solution Approach 2:
The patent extracts the particle size reduction function from the traditional multi-step process (milling followed by dissolution) and integrates it into the microfluidization process. This extraction and integration eliminates discontinuous processing steps while maintaining the beneficial particle size reduction effect.
4Device complexity
If conventional stirred tank preparation is used, then equipment is simple, but low solubility APIs require very low concentrated/high volume spray solutions
Solution Approach 1:
The patent replaces the conventional stirred tank with a microfluidization system that uses high-pressure fluid dynamics to achieve superior mixing and dissolution. This substitution enables the preparation of high-concentration spray solutions for low solubility APIs by creating intense local mixing zones and enhancing mass transfer, eliminating the need for large volumes of dilute spray solution.
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 process enables rapid and efficient preparation of amorphous solid dispersions with improved bioavailability, scalable production, and reduced stability issues, as it continuously feeds a homogeneous spray solution to a spray dryer, eliminating the need for external heat and additional processing steps.
Implementation Method 1
A continuous spray drying process that uses microfluidization to micronize and homogenize a suspension of active pharmaceutical ingredients and excipients within a micro-reactor or micro-channel
Implementation Method 2
the spray solution is fed through an atomization nozzle to a spray drying chamber where the solvent is evaporated from the fine droplets by the hot drying gas to produce solid particulates
Data Source
AI summary
The present invention discloses a spray drying process characterized by continuous preparation and immediate spray drying of a solution comprising at least one active pharmaceutical ingredient and/or at least one excipient, and at least one solvent. The said active pharmaceutical ingredient(s) and solvent(s) are combined, alone or along with one or more excipients to form a first suspension. Said suspension is continuously fed to an intensifier pump that pushes said suspension through at least one micro-reaction chamber and/or at least one micro-channel where the suspension's solid(s) component(s) is(are) dissolved into said solvent(s) by means of high energy mixing I forced contact at micro, nano and molecular level to form a solution stream. The said solution stream is then immediately and continuously fed to the spray dryer through at least one atomization nozzle, drying said atomized stream to obtain solid particles and collecting said solid particles. Single component particles or multi-component particles, particulate amorphous solid dispersion and pharmaceutical compositions are also disclosed. The present invention also discloses amorphous solid dispersions obtained by the method of the invention as well as pharmaceutical compositions containing the same.