Scale-up of agitated drying: Effect of shear stress and hydrostatic pressure on active pharmaceutical ingredient powder properties

AIChE Journal ◽  
2014 ◽  
Vol 61 (2) ◽  
pp. 407-418 ◽  
Author(s):  
Brenda Remy ◽  
Weston Kightlinger ◽  
Eric M. Saurer ◽  
Nathan Domagalski ◽  
Benjamin J. Glasser
Keyword(s):  
Shear Stress ◽  
Hydrostatic Pressure ◽  
Scale Up ◽  
Active Pharmaceutical Ingredient ◽  
Powder Properties

Impact of agitated drying on the powder properties of an active pharmaceutical ingredient

2011 ◽  
Vol 210 (3) ◽  
pp. 308-314 ◽  
Author(s):  
E. Kougoulos ◽  
C.E. Chadwick ◽  
M.D. Ticehurst
Keyword(s):  
Active Pharmaceutical Ingredient ◽  
Powder Properties

Transverse shear stress within surface layer and its effects

2019 ◽  
Vol 25 (2) ◽  
pp. 166-180
Author(s):  
Ge Yan ◽  
Zaixing Huang
Keyword(s):  
Shear Stress ◽  
Surface Layer ◽  
Hydrostatic Pressure ◽  
Transverse Shear ◽  
Transverse Shear Stress ◽  
Middle Section ◽  
Nanoscale Solids ◽  
Maximal Stress

When the transverse shear stress within a surface layer is taken into account, what happens in the deformation of micro- or nanoscale solids? The relevant problems are investigated by analyzing the deformation of a micro- or nanosized solid ellipsoid. The results show that both the stress and the deformation of a micro- or nanosized ellipsoid increase after the transverse shear stress within the surface layer is introduced, and that the maximal stress always occurs at both ends of the long axis of the ellipsoid. Unlike the prediction given by the Gurtin–Murdoch model, the calculation coming from the model of this paper predicts that the micro- or nanosized ellipsoid subjected to hydrostatic pressure contracts radially in the middle section and expands radially on both sides of the middle section. This difference provides an experimental standard to verify two models.

Preparation of the HIV Attachment Inhibitor BMS-663068. Part 9. Active Pharmaceutical Ingredient Process Development and Powder Properties

2017 ◽  
Vol 21 (8) ◽  
pp. 1174-1185 ◽  
Author(s):  
Thomas E. La Cruz ◽  
Eric M. Saurer ◽  
Joshua Engstrom ◽  
Michael S. Bultman ◽  
Robert Forest ◽  
...  
Keyword(s):  
Process Development ◽  
Active Pharmaceutical Ingredient ◽  
Powder Properties

Non-Newtonian Flow Behavior in Microchannels for Emulsion Formation

2006 ◽  
Author(s):  
Ravi Arora ◽  
Eric Daymo ◽  
Anna Lee Tonkovich ◽  
Laura Silva ◽  
Rick Stevenson ◽  
...  
Keyword(s):  
Shear Stress ◽  
Pressure Drop ◽  
Wall Shear Stress ◽  
Power Law ◽  
Flow Behavior ◽  
Scale Up ◽  
High Wall Shear Stress ◽  
Shear Rates ◽  
Wall Shear ◽  
Low Shear

Emulsion formation within microchannels enables smaller mean droplet sizes for new commercial applications such as personal care, medical, and food products among others. When operated at a high flow rate per channel, the resulting emulsion mixture creates a high wall shear stress along the walls of the narrow microchannel. This high fluid-wall shear stress of continuous phase material past a dispersed phase, introduced through a permeable wall, enables the formation of small emulsion droplets — one drop at a time. A challenge to the scale-up of this technology has been to understand the behavior of non-Newtonian fluids under high wall shear stress. A further complication has been the change in fluid properties with composition along the length of the microchannel as the emulsion is formed. Many of the predictive models for non-Newtonian emulsion fluids were derived at low shear rates and have shown excellent agreement between predictions and experiments. The power law relationship for non-Newtonian emulsions obtained at low shear rates breaks down under the high shear environment created by high throughputs in small microchannels. The small dimensions create higher velocity gradients at the wall, resulting in larger apparent viscosity. Extrapolation of the power law obtained in low shear environment may lead to under-predictions of pressure drop in microchannels. This work describes the results of a shear-thinning fluid that generates larger pressure drop in a high-wall shear stress microchannel environment than predicted from traditional correlations.

scholarly journals Hydrostatic pressure regulates CYP1A2 expression in human hepatocytes via a mechanosensitive aryl hydrocarbon receptor-dependent pathway

2020 ◽  
Vol 318 (5) ◽  
pp. C889-C902
Author(s):  
Lewis Burton ◽  
Paula Scaife ◽  
Stuart W. Paine ◽  
Howard R. Mellor ◽  
Lynn Abernethy ◽  
...  
Keyword(s):  
Shear Stress ◽  
Hydrostatic Pressure ◽  
Primary Source ◽  
Human Hepatocytes ◽  
Metabolic Clearance ◽  
Dependent Manner ◽  
Aryl Hydrocarbon ◽  
Albumin Production

Approximately 75% of xenobiotics are primarily eliminated through metabolism; thus the accurate scaling of metabolic clearance is vital to successful drug development. Yet, when data is scaled from in vitro to in vivo, hepatic metabolic clearance, the primary source of metabolism, is still commonly underpredicted. Over the past decades, with biophysics used as a key component to restore aspects of the in vivo environment, several new cell culture settings have been investigated to improve hepatocyte functionalities. Most of these studies have focused on shear stress, i.e., flow mediated by a pressure gradient. One potential conclusion of these studies is that hepatocytes are naturally “mechanosensitive,” i.e., they respond to a change in their biophysical environment. We demonstrate that hepatocytes also respond to an increase in hydrostatic pressure that, we suggest, is directly linked to the lobule geometry and vessel density. Furthermore, we demonstrate that hydrostatic pressure improves albumin production and increases cytochrome P-450 (CYP) 1A2 expression levels in an aryl hydrocarbon-dependent manner in human hepatocytes. Increased albumin production and CYP function are commonly attributed to the impacts of shear stress in microfluidic experiments. Therefore, our results highlight evidence of a novel link between hydrostatic pressure and CYP metabolism and demonstrate that the spectrum of hepatocyte mechanosensitivity might be larger than previously thought.

Sign in / Sign up

Export Citation Format

Share Document