Proof-of-Concept Design of an In-Line pH Neutralization System with Coarse and Fine Adjustments for the Continuous Manufacturing of Pharmaceuticals

Wen, Kai; Hu, Chuntian; Wu, Wei; Shvedova, Khrystyna; Born, Stephen C.; Takizawa, Bayan; Mascia, Salvatore

doi:10.1021/acs.oprd.1c00101

Cited by 4 publications

(6 citation statements)

References 36 publications

(54 reference statements)

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“…Furthermore, a large difference between the p K a of HCl (−6.3) and set point pH of 7 makes it challenging to control pH in continuous experiments where a slight deviation/fluctuation in the pump flow rate is detrimental. For better pH control, the difference between the desired pH (7 in the present case) and the p K a of the acidifying agent should be minimal . The examination of p K a values of different acids viz.…”

Section: Resultsmentioning

confidence: 95%

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO₂ as an Acidifying Agent

Shukla,

Moghadam,

Patwardhan

et al. 2024

ACS Sustainable Chem. Eng.

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Section: Resultsmentioning

confidence: 95%

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO₂ as an Acidifying Agent

Shukla,

Moghadam,

Patwardhan

et al. 2024

ACS Sustainable Chem. Eng.

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“…Finally, different types of pumps can be employed to fine tune a given application. [162] When making tablets for ultra-lowdose drugs using twin-screw wet granulation, Démuth et al showed that syringe pumps generated lower deviation of drug content in tablets compared to peristaltic or piston-driven pumps. This is important as ultra-low-dose drugs require higher degrees of precision versus normal dosages.…”

Section: Pumpingmentioning

confidence: 99%

“…By integrating pumps with in‐line monitoring and control, they were able to control the pH fluctuation within 2 pH units near the equivalence point. Finally, different types of pumps can be employed to fine tune a given application [162] . When making tablets for ultra‐low‐dose drugs using twin‐screw wet granulation, Démuth et al .…”

Section: Unit Operationsmentioning

confidence: 99%

Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

Hyer,

Gregory,

Kay

et al. 2024

Adv Synth Catal

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The pharmaceutical industry has traditionally employed batch processing as a means of synthesizing active pharmaceutical ingredients (APIs) on a commercial scale. Batch manufacturing enables API synthesis in large quantities in order to meet regulations. Yet, this strategy remains cumbersome, is labor‐intensive, and creates complex logistical networks. In recent decades, batch API processing has gradually eroded American economic competitiveness and has led to the off‐shoring of API manufacturing from the United States. Today it is estimated that +80% of APIs are manufactured overseas. Meanwhile, disruptions from the Coronavirus Disease (SARS‐CoV‐2) have exacerbated weaknesses in the global supply chain, culminating with widespread shortages of critical life‐saving drugs. These shortages have emphasized the importance of reshoring drug manufacturing to the U.S. and fostered a regulatory landscape that seeks advanced methods of API manufacturing in order to bolster America’s supply chain resiliency. Recently, increased attention has been directed towards continuous drug manufacturing to enable nonstop API production within modular stand‐alone flow systems. Continuous manufacturing (CM) facilitates modular automation, offers new avenues towards process intensification, and even enables in‐line analytical monitoring from raw materials to packaged products. This strategy offers better conversion, increased safety, reduced waste, and overall cost savings versus traditional batch‐style processing. The rise of advanced API manufacturing, coupled with the current regulatory landscape, offers a rare window of opportunity to convert traditional batch pharmaceutical processes into continuous, streamlined production systems to on‐shore API manufacturing and eliminate drug shortages. This review will outline the current state‐of‐the‐art in the CM of APIs and will highlight the translation of chemistry and unit operations from batch processes to modular CM systems.

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“…In-line pH sensors, designed for continuous data measurement, have been used in the biotech and pharmaceutical industries for a number of years [48][49][50]. However, there are a limited number of electrode systems capable of providing in-situ pH measurements at temperatures greater than 100 • C and at pressures greater than saturated water pressure.…”

Section: Industrial Applications Of In-line Ph Measurement Under Chal...mentioning

confidence: 99%

pH, the Fundamentals for Milk and Dairy Processing: A Review

Aydogdu

O’Mahony

McCarthy

2023

Dairy

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The ability to measure and capture real-time unit operational data has significant benefits during dairy processing, whether it is the basics, such as measuring temperature, pressure, and flow rates, or more recent developments in the case of in-line viscosity and product-compositional measurements. This rapid data collection has helped increase profitability by reducing energy costs, minimizing product loss, and allowing automated control. Advances in technology have allowed for in-line measurements of the composition and some physical attributes such as particle size and viscosity; however, an attribute that spans both compositional and physical attributes is pH, directly influenced by composition but also environments, such as temperature and dry matter content. pH is measured for a plethora of reasons, such as a measure of milk quality (microbial spoilage), acidification of casein, cheese production, maintaining optimum conditions during protein hydrolysis, etc. However, very little is published on the fundamentals of pH and pH measurement in dairy processing; rather, it is usually a cause-and-effect phenomenon. This review visits one of the oldest analytical considerations in the dairy industry and re-examines how it is affected by product composition and processing conditions.

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Proof-of-Concept Design of an In-Line pH Neutralization System with Coarse and Fine Adjustments for the Continuous Manufacturing of Pharmaceuticals

Cited by 4 publications

References 36 publications

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO₂ as an Acidifying Agent

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO₂ as an Acidifying Agent

Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

pH, the Fundamentals for Milk and Dairy Processing: A Review

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Proof-of-Concept Design of an In-Line pH Neutralization System with Coarse and Fine Adjustments for the Continuous Manufacturing of Pharmaceuticals

Cited by 4 publications

References 36 publications

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO2 as an Acidifying Agent

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO2 as an Acidifying Agent

Continuous Manufacturing of Active Pharmaceutical Ingredients: Current Trends and Perspectives

pH, the Fundamentals for Milk and Dairy Processing: A Review

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Product

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Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO₂ as an Acidifying Agent

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO₂ as an Acidifying Agent