This work investigates the application
of static mixers (SMs) in
precipitating environments as present in certain pharmaceutical processes,
in which the undesired side effect of precipitation of the residual
dissolved fraction leads to equipment fouling and process stability
challenges. The tests were conducted using saturated suspensions mixed
with an anti-solvent to challenge the system with a step change of
solubility in the presence of seeds and SMs. Various equipment configurations
such as co-axial vs perpendicular mixing, different equipment dimensions,
plastic vs metal SM, or ultrasound (US) irradiation were investigated,
and fouling probability and stability were analyzed for different
precipitation rates by monitoring the pressure level. The process
stability was highly influenced by the setup configuration. The most
stable and satisfactory process was achieved by co-axial mixing of
the fluids before the SM plus using US irradiation. With this setup
a run time of 5 h was achieved, continuous processing beyond 5 h could
be realized by parallel arrangement of SMs, in which the process is
switched from one SM to another after a pressure threshold is triggered.
Furthermore, the particle size in various feed and outlet suspensions
was analyzed, and correlations between the amount of suspended particles
and the particle growth were determined. The highest initial solids
in the feed suspension (30 wt%) resulted in the smallest growth of
the particles in the outlet suspension (d
50 increased by 17.7%) after anti-solvent addition.
This work addresses the influence of several process parameters on the performance of a novel drying device (patent NL2020740B1). In the new dryer, the processed substance is conveyed through the grooves of a large rotor via an interlocking screw design. A gentle, forced flow is created, preventing agglomeration and attrition and enabling a new technology of continuous drying for poorly flowing substances, which are often applied in the pharmaceutical industry. Drying test runs are performed using waterwetted ibuprofen, a nonsteroidal anti-inflammatory drug with poor material flow properties. The substances were tested according to their size, shape, and flow properties prior to the test runs. The process parameters in question were the temperature, mass flow, air flow, rotational speed, and initial moisture. Additionally, test runs to estimate the drying mechanism and the long-term process behavior, as well as reprocessing tests of the substance ibuprofen, were executed. It was shown that the dryer's performance for cohesive materials was optimal (continuous process times of up to 10 h were possible with evaporation rates up to 688 g/h). The process was robust, with a few drawbacks related to materials that are prone to tribocharging.
The goal of this
investigation was to develop a continuous process
for producing as much dry material as possible under stable operating
conditions in an intentionally or unintentionally precipitating environment.
Despite the challenge of solids formation, the risk of fouling, and
as a result clogging of the system, the goal was achieved by maximizing
uninterrupted runtime. A novel approach was used, i.e., exciting the
mixing zone by ultrasound (US) in a specially configured process chamber.
The main focus was the investigation of how to avoid fouling and buildup
of solids in the process chamber, which are undesired effects in continuous
manufacturing. Often these are unavoidable side effects in a precipitating
environment, which in the worst case can lead to a process shutdown.
In this work, two model substance combinations were used (lactose/water/isopropanol
and ibuprofen/ethanol/water) to demonstrate a hydrophilic case and
a lipophilic case. A feed suspension was mixed with an antisolvent
in an ultrasonic process chamber, with a persisting helical flow pattern
and perpendicular introduction of ultrasound. Solids were precipitated
during mixing, and blockage of the system could occur as a result
of the introduced fouling and accumulation. Critical process parameters
(product temperature, US input, and solid loading) were analyzed with
respect to their influence on process stability and duration. As this
process could also be applied to produce or purify particles, the
particle size distributions (PSDs) of the two substances were evaluated
with regard to agglomeration and attrition. The described precipitating
environment can be applied to pharmaceutical manufacturing.
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