TY - JOUR
T1 - Runtime Maximization of Continuous Precipitation in an Ultrasonic Process Chamber
AU - Zettl, Manuel
AU - Kreimer, Manuel
AU - Aigner, Isabella
AU - Mannschott, Thomas
AU - van der Wel, Peter
AU - Khinast, Johannes
AU - Krumme, Markus
PY - 2020/4/17
Y1 - 2020/4/17
N2 - 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.
AB - 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.
KW - precipitation
KW - mixing
KW - ultrasound application
KW - suspensions
KW - crystallization
UR - http://www.scopus.com/inward/record.url?scp=85084678062&partnerID=8YFLogxK
U2 - 10.1021/acs.oprd.9b00311
DO - 10.1021/acs.oprd.9b00311
M3 - Article
SN - 1083-6160
VL - 24
SP - 508
EP - 519
JO - Organic Process Research & Devlopment
JF - Organic Process Research & Devlopment
IS - 4
ER -