Fluid Bed Processing of Pharmaceuticals

Processing Modules

Dryer: warm air is blown through a perforated distributor to rapidly and gently dry materials until the required residual moisture content is reached. Moisture evaporated from the product is exhausted with the drying air, providing very short processing times.

Precision Granulator: a novel granulation process, a rotating high velocity air stream is established in the central agglomeration tube. Particles are picked up at the base of the tube and accelerated by the air stream. The particles come into contact with liquid droplets produced from the spray nozzle at the base of the tube. The relative velocity of the air, liquid droplets and particles are high, so wetting is efficient and drying begins almost immediately. Most of the feed material is in the outer “holding area,” where the gas velocity is very low. Attrition is greatly reduced. The gas humidity is also low in the holding area so the material is dry not sticky. Individual particles may make repeated cycles (typically from 10 to 1000) through the tube, allowing very large agglomerates to be built up.

Top Spray Granulator: offering granulation and drying in a single-pot process, the top spray granulator agglomerates finer particles into larger, free flowing granulates. Ingredients are mixed and pre-heated by an upward flow of heated air. Granulation occurs by spraying liquid into the fluidized powder. The granules are subsequently dried with heated air. The top spray granulator can also be used for top spray coating, layering from liquid, and instantizing. 

Spray Dryer Granulator: with batch or continuous discharge available in continuous mode, the spray dryer granulator transforms suspensions or solutions into dry, free-flowing, dustless granules. A suspension or solution of the substance to be dried is sprayed onto warm air, simultaneously drying and agglomerating the product. The product is discharged at a controlled rate to maintain an optimum bed height. Special features include easy scale-up and a small footprint.

PRECISION-COATER: this multi-functional fluid bed processor can be used to make pellets by layering the active material onto an inert core. Offering high spray rates for short processes, non-pareil starter pellets are sprayed with a solution or suspension of the active material and dried simultaneously.

Production Capacities

Key Advantages of FlexStream

• Reduced investment 
• Easy/fast changeover 
• Reduced downtime 
• Flexible fluid bed concept for drying, granulation and pellet coating 
• Linear scale-up
  
• Compact design
• Cost saving.

Where inspiration meets technology

Inspired processing of effervescents - with FlexStream fluid bed granulation technology.

• Suitable for all effervescent formulations with aqueous and/or organic based solvents. 
• Robust processor granulating free flowing products with no lumps. 
• Substantial faster process compared to traditional effervescent processing methods. 
• Lowest total costs for high quality effervescent processing.

Process Control

Process Monitoring

The programmable logic controller (PLC) front panel keypad and built-in monitor are used for recipe input and real-time process MIMIC display. For optimum compatibility with existing plant control strategies, fluid bed systems are available with a choice of manual or automated FDA-compliant controls. PLC and PC-based options offer a wide range of recipe handling, data acquisition and network communication functions.

The FDA’s PAT (process analytical technology) initiative has enabled GEA to combine its equipment design skills and process engineering know-how to integrate online (PAT) analyzers into its process systems in a way that can provide real insight into the operation of the process and help customers achieve key product quality targets.

The goal of the PAT initiative is to ensure that pharmaceutical products are manufactured using processes that are understood and monitored, and that key product quality characteristics can be actively controlled. 

Combining process monitoring using online analyzers, together with solid process engineering principles and advanced modelling techniques, will enable processes to be actively controlled to compensate for minor input variations (raw materials), so that final product specifications will be closer to ideal targets. 

Using process models to identify the conditions in which products perform best in subsequent procedures will enable the whole production process to be targeted towards the performance of the final dose, rather than just optimizing each unit operation individually. GEA's wide scope gives it a unique perspective on the entire process.

Lighthouse Probe® Technology

GEA has created a compact and cleanable in-process optical probe for use in powder processing equipment. The result is the novel Lighthouse Probe®, which can be used with a range of spectroscopic techniques, including NIR and UV/vis, to overcome the traditional problem of product sticking to observation windows. 

The probe is compact and easy to install, and makes it possible to take a reliable in-process measurement of quality critical product characteristics, including

• material and active content identification 
• active content uniformity during high shear blending operations 
• moisture content and end-point during drying processes 
• coat growth during coating processes.

Optical methods such as UV/vis or NIR spectroscopy can be very powerful tools to analyze a range of product characteristics.  In processes involving wet and sticky powders, however, it is necessary to ensure that the system has a clear view of the product. Conventional windows used in process equipment such as fluid bed systems or high shear granulators have always suffered from the risk of window fouling. The new Lighthouse Probe® has overcome this problem.

Plant Design

Through-the-Wall Installation

By positioning the support column at the back of the fluid bed, a through-the-wall installation is achieved that ensures that all the auxiliary equipment is housed outside the process room. This greatly simplifies compliance with GMP guidelines.

Solvent Emission Control

Spraying Systems

Product Discharge

For automatic product discharge, pneumatic conveying or gravity-based systems are available for use with the Non-Sifting Gill Plate air distributor technology.

Inlet Air Preparation Unit

Inlet air is treated using a series of filters and conditioning units according to the sensitivity of the process and the ambient climatic conditions. Options range from the basic minimum, consisting of a pre-filter, heater and final filter, to full air-conditioning to provide consistent processing conditions all year round. Condensers are used for dehumidifying in most applications, but for hygroscopic or effervescent products that require a very low dew point, additional adsorption devices can be installed. Humidification is achieved by an injection of steam.

Process Filters

In granulation, drying and most pelletizing applications, a process filter is used to trap small particles, which are subsequently returned to the bed when the filter is cleaned. In coating applications, fine particles usually need to be removed. Fluid beds that are used for more than one type of process can be supplied with interchangeable process filters.

Filter Options

Single shaker bag filter: a simple, basic filter with a single bag, which is cleaned by shaking. Fluidization stops during filter cleaning.

Multi-shaker bag filter: this filter is divided into two or more sections, with a separate filter bag in each one. Bags are cleaned individually by shaking the filter, while fluidization continues in the other sections, for faster and more efficient production.

Blow-back filter: there are multiple filter bag sections in this design. Cleaning takes place one bag at a time, so that a large proportion of the filter is always available for continuous fluidization.

Cartridge filter: stainless steel filter cartridges are cleaned one at a time, so that a large proportion of the filter is always available for continuous fluidization. Unlike bag filters, this system can be cleaned-in-place.

High Equipment Costs vs Operator Friendly Working Environments

• Better containment technology allows operators to work outside of containment suites
• Operators are less restricted, allowing a more efficient working environment 
• Low risk of re-contamination 
• Development of more potent products/compounds 
• More stringent regulations 
• Better housekeeping.