Continuous Active Ingredient Granulation for Improved Flowability
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Solution Overview
Problem
Existing processes for producing dosage forms of active pharmaceutical ingredients with poor flowability, particularly those requiring high active ingredient content, face challenges in achieving high throughput, yield, and satisfactory granule properties such as particle size, moisture content, and bulk density, while ensuring stability and preventing aggregation.
Innovation Solution
A continuous process involving the introduction of droplets of a solution or suspension containing the active ingredient into a process chamber, guided by a process gas, allowing for controlled particle growth through repeated deposition and evaporation, resulting in granules with improved flowability and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If active ingredient powders are produced by spray-drying, then the active ingredient can be converted into a processable form, but the resulting fine powders have poor flowability and low stability
Solution Approach 1:
The invention combines the active ingredient with excipients (such as mannitol, lactose, or microcrystalline cellulose) to form composite granules. This composite structure provides the mechanical strength and flowability characteristics of the excipient while maintaining the active ingredient's therapeutic function, thereby resolving the contradiction between processability and reliability
Solution Approach 2:
The invention changes the physical parameters of the active ingredient by granulating it into particles with specific size ranges (d10: 50-150 μm, d50: 200-400 μm, d90: 500-800 μm) and controlling moisture content (1-5%). These parameter changes transform the poor-flowing fine powder into stable granules with improved handling properties
2Ease of operation
If batch processes are used for granule production, then the process is simple to operate, but the throughput and productivity are limited
Solution Approach 1:
The invention implements a continuous granulation process where active ingredient powder, excipients, and binding solution are continuously fed into a fluidized bed granulator. The granules are continuously grown, dried, and discharged, eliminating batch-to-batch interruptions and significantly increasing throughput while maintaining operational simplicity through automated continuous feeding and processing
3Quantity of substance
If high active ingredient content (>50 wt.%) is targeted in dosage forms, then the dosage form efficiency is improved, but the flowability and manufacturability become more difficult to achieve
Solution Approach 1:
The invention uses excipients as intermediary materials that facilitate the manufacturing process. These excipients act as carriers and flowability enhancers, allowing high concentrations of active ingredient to be incorporated while maintaining adequate flow properties for tablet compression. The excipient matrix provides the necessary rheological properties for processing
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 process enables the production of granules with enhanced flowability and stability, suitable for high active ingredient content dosage forms, allowing for efficient processing into tablets and controlled-release formulations.
Implementation Method 1
introduction of droplets of a solution or suspension containing the active ingredient into a process chamber in which liquid evaporates
Implementation Method 2
particles already present in the process chamber come into contact with droplets which still contain at least enough liquid to be deposited on the particles
Data Source
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AI summary
The invention relates to a method for continuously producing an active ingredient granulate, having the following steps: (a) producing a spray composition in which an active ingredient and optionally one or more auxiliary agents are dissolved or dispersed in a liquid; (b) providing solid particles in a processing chamber; (c) introducing drops made of the spray composition into an injection zone of the processing chamber in which the liquid is evaporated; (d) repeatedly guiding the solid particles past injected drops in the processing chamber using a processing gas jet such that at least a proportion of the drops which could have already lost some of the contained liquid is brought into contact with solid particles, and larger solid particles are formed by attachment; and (e) removing the active ingredient granulate from the processing chamber in the form of solid particles, wherein the active ingredient has a Hausner ratio of 1.19 or more when used.