Continuous Active Ingredient Granulation for Poor-Flow Powders
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Solution Overview
Problem
Existing methods for producing granules of active pharmaceutical ingredients with poor flowability, such as those with a Hausner factor of 1.19 or greater, often result in unsatisfactory flowability and stability, making it difficult to process them into dosage forms with high active ingredient content.
Innovation Solution
A continuous method involving the introduction of active ingredient-containing droplets into a spouted bed process space, where droplets evaporate and agglomerate with existing particles, allowing controlled particle growth and formation of granules with improved flowability and stability, suitable for high active ingredient content dosage forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Shape
If active ingredient powders are produced by spray-drying, then the active ingredient can be obtained in particle form, but the particles have poor flowability and tend to aggregate and clump
Solution Approach 1:
The invention segments the spray-drying process into two distinct stages: (1) initial particle formation by spray-drying to create fine particles, and (2) subsequent granulation in a fluidized bed to aggregate these particles into larger granules with improved flowability. This segmentation allows each stage to optimize for its specific function, resolving the contradiction between particle formation and flowability.
Solution Approach 2:
The invention implements a continuous process where spray-dried particles are directly fed into the fluidized bed granulation system without interruption. This continuous action ensures that the fine particles are immediately processed into flowable granules, preventing aggregation and clumping while maintaining production efficiency.
2Ease of manufacture
If fine particle forms of active ingredients are used, then the active ingredient can be readily formulated, but the fine powders have poor stability and tend to aggregate and clump
Solution Approach 1:
The process segments particle formation and stability enhancement into separate stages: spray-drying creates the fine particles for formulability, while fluidized bed granulation subsequently aggregates these particles into stable granules that resist aggregation and clumping during storage and handling.
Solution Approach 2:
The spray-drying stage performs preliminary particle formation, creating fine particles with good formulability. These particles are then immediately subjected to granulation in the fluidized bed, which preliminarily stabilizes them before final formulation, preventing aggregation and clumping.
3Ease of operation
If batch methods are used for granule production, then the process is simple to operate, but the granules obtained do not always have satisfactory properties with regard to flowability and stability
Solution Approach 1:
The invention transitions from batch to continuous operation, where spray-dried particles continuously feed into the fluidized bed granulation system. This continuous process ensures consistent granule properties with satisfactory flowability and stability, while maintaining operational simplicity through automated continuous processing.
4Quantity of substance
If active ingredients with poor flowability (Hausner factor ≥1.19) are used, then the active ingredient can be obtained in high purity form, but it is difficult to process into dosage forms with high active ingredient content
Solution Approach 1:
The process segments the material transformation into two stages: first obtaining high purity active ingredient particles through spray-drying, then improving their processability by aggregating them into flowable granules through fluidized bed granulation. This segmentation preserves purity while enhancing processability.
Solution Approach 2:
The invention changes the physical parameters of the active ingredient by transforming it from fine particles (poor flowability, Hausner factor ≥1.19) into larger granules with improved flowability and handling characteristics, while maintaining high active ingredient content suitable for dosage form manufacturing.
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 enables the production of granules with enhanced flowability and stability, suitable for high active ingredient content dosage forms, and allows for the creation of controlled-release formulations that release the active ingredient in specific gastrointestinal sections.
Implementation Method 1
introducing droplets of the spray composition into an injection zone of the process space in which the liquid evaporates
Implementation Method 2
providing solid particles in a spouted bed process space
Implementation Method 3
at least a portion of the droplets, which may have already lost part of the liquid contained, comes into contact with solid particles and larger solid particles are formed through agglomeration
Data Source
AI summary
A method for the continuous production of an active ingredient granulate is provided, which comprises the following steps:(a) preparing a spray composition by dissolving or dispersing an active ingredient and optionally one or more excipients in a liquid;(b) providing solid particles in a process space;(c) introducing droplets of the spray composition into an injection zone of the process space in which the liquid evaporates;(d) repeatedly guiding the solid particles back past the sprayed droplets in the process space with the aid of a process gas jet, so that at least a portion of the droplets, which may have already lost part of the liquid contained, comes into contact with solid particles and larger solid particles are formed through agglomeration;(e) removing the active ingredient granulate from the process space in the form of solid particles,wherein the active ingredient in the form used has a Hausner factor of 1.19 or greater.