modeling phase separation risk during spray drying from
TRANSCRIPT
Modeling Phase Separation Risk During Spray Drying from Mixed
SolventsJonathan Cape | Lonza Rapid Fire Presentation | 2020
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Session Description and Objectives
Solvent Selection is a critical decision point in process development for spray dried amorphous dispersions. Low organic solubility compounds often require the use of mixed solvents to increase solubility, though their use can create phase separation risks during drying. A model is presented that aids solvent selection by assessing the thermodynamic landscale for phase separation and identifying low risk solvent compositions for processing.
Learning
Objectives:
compositions
Apply modeling tools to a representative quaternary spray solution system
Biography and Contact Information
Ph.D. in Biochemistry and Biophysics (2006) from Washington State University
Research Interests:
• Kinetic modeling of drug release mechanisms from MR dosage forms
• Analytical approaches to aid process understanding
Post-doctoral studies at WSU and Los Alamos National Laboratory.
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Bioavailability Enhancement with Amorphous Solid Dispersions
Amorphous Solid Dispersions (ASDs) are a highly successful approach to improving the bioavailability of low aqueous solubility compounds
Development of successful ASD intermediates can be challenging
Amorphous dispersions
increase solubility…
Bioavailability Enhancement with Amorphous Solid Dispersions
Stability • Physical
• Permeation
• Sustainment
Spray Drying is one of the more prevalent process approaches used to produce ASDs
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Solvent Selection – a Key Decision Point in Spray Drying Process Development
Solvent Selection has large
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Solubility Slump Solubility BUMP
0.0001
0.001
0.01
0.1
1
10
100
acetone solubility, mg/mL 95/5 or 90/10 acetone/water solub, mg/mL water solubility mg/mL
API Solubility in Acetone/Water Mixed Sovlents
Mixed solvents systems can improve starting
spray solution solubility and therefore improve
process throughput
Mixed solvent systems can also become poor
solvents as lower volatility components are
enriched during drying (e.g. water)
Optimization Problem
• Least risk to physical state
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Drying Model with Phase State Calculation as a Risk Assessment Tool for Solvent Selection
A “minimal” drying model for
a four-component system has
droplet during the drying
Flory Huggins calculation for
Composition of Droplet During Drying
(80% Methanol, 20% Water Solvent System)
Composition of Droplet During Drying
(85% Methanol / 15% H2O Solvent System)
Application of the Drying Model to Solvent Selection for the Ritonavir / PVP-VA / Methanol / Water System
0
10
20
30
40
50
60
70
80
90
% C
% C
does this
increase Φ
separation risk?
In order to test the utility of the model, we have applied it to a model system (RTV / PVPVA / MeOH / H2O), which
undergoes amorphous phase separation in certain MeOH/H2O solvent systems
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Application of the Drying Model to Solvent Selection for the Ritonavir / PVP-VA / Methanol / Water System
In the case of the (RTV /
PVPVA / MeOH / H2O)
solubility boundary is
encountered at about
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Application of the Drying Model to Solvent Selection for the Ritonavir / PVP-VA / Methanol / Water System
Experimentally, the onset
enthalpy peak occurs
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Drying Model with Phase State Calculation as a Risk Assessment Tool for Solvent Selection
Recap of
Spray drying process throughput can be optimized by choosing
a solvent that exhibits optimal process characteristics (low ΔHvap,
high P, low viscosity) and solubility for the API / polymer system
Mixed solvent systems can improve solubility for low organic
solubility APIs, but can also lead to phase separation risks due
to differential drying rates
Kinetic modeling of the drying process allows compositional
trajectories to be assessed, which can then be plotted against a
quaternary phase diagram to identify high risk solvent systems
to avoid during process development
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Disclaimer and Forward-looking statements This presentation (“Presentation”) is the property of Lonza AG and its affiliates (“Lonza”) and any unauthorized use or interception of this Presentation is illegal.
The information contained herein are believed to be correct. However, no warranty is made, either expressed or implied, regarding its accuracy or the results to be obtained from the use of such information. Lonza disclaims any liability for the use of this presentation and the use of the information contained herein is at your own risk. All trademarks belong to Lonza or its affiliates or to their respective third party owners and are only being used for informational purposes. All copyrighted material has been reproduced with permission
from their respective owners, all other materials ©2020 Lonza. All rights reserved. Certain matters discussed in this Presentation may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd., although Lonza Group Ltd. can give no assurance that these expectations and estimates will be achieved. Investors are cautioned that all forward-looking statements involve risks and uncertainty and are qualified in their entirety. The actual results may differ materially in the future from the forward-looking statements included in this Presentation due to
various factors. Furthermore, except as otherwise required by law, Lonza Group Ltd. disclaims any intention or obligation to update the statements contained in this Presentation.
www.pharma.lonza.com Contact Us - click here
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Session Description and Objectives
Solvent Selection is a critical decision point in process development for spray dried amorphous dispersions. Low organic solubility compounds often require the use of mixed solvents to increase solubility, though their use can create phase separation risks during drying. A model is presented that aids solvent selection by assessing the thermodynamic landscale for phase separation and identifying low risk solvent compositions for processing.
Learning
Objectives:
compositions
Apply modeling tools to a representative quaternary spray solution system
Biography and Contact Information
Ph.D. in Biochemistry and Biophysics (2006) from Washington State University
Research Interests:
• Kinetic modeling of drug release mechanisms from MR dosage forms
• Analytical approaches to aid process understanding
Post-doctoral studies at WSU and Los Alamos National Laboratory.
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Bioavailability Enhancement with Amorphous Solid Dispersions
Amorphous Solid Dispersions (ASDs) are a highly successful approach to improving the bioavailability of low aqueous solubility compounds
Development of successful ASD intermediates can be challenging
Amorphous dispersions
increase solubility…
Bioavailability Enhancement with Amorphous Solid Dispersions
Stability • Physical
• Permeation
• Sustainment
Spray Drying is one of the more prevalent process approaches used to produce ASDs
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Solvent Selection – a Key Decision Point in Spray Drying Process Development
Solvent Selection has large
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Solubility Slump Solubility BUMP
0.0001
0.001
0.01
0.1
1
10
100
acetone solubility, mg/mL 95/5 or 90/10 acetone/water solub, mg/mL water solubility mg/mL
API Solubility in Acetone/Water Mixed Sovlents
Mixed solvents systems can improve starting
spray solution solubility and therefore improve
process throughput
Mixed solvent systems can also become poor
solvents as lower volatility components are
enriched during drying (e.g. water)
Optimization Problem
• Least risk to physical state
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Drying Model with Phase State Calculation as a Risk Assessment Tool for Solvent Selection
A “minimal” drying model for
a four-component system has
droplet during the drying
Flory Huggins calculation for
Composition of Droplet During Drying
(80% Methanol, 20% Water Solvent System)
Composition of Droplet During Drying
(85% Methanol / 15% H2O Solvent System)
Application of the Drying Model to Solvent Selection for the Ritonavir / PVP-VA / Methanol / Water System
0
10
20
30
40
50
60
70
80
90
% C
% C
does this
increase Φ
separation risk?
In order to test the utility of the model, we have applied it to a model system (RTV / PVPVA / MeOH / H2O), which
undergoes amorphous phase separation in certain MeOH/H2O solvent systems
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Application of the Drying Model to Solvent Selection for the Ritonavir / PVP-VA / Methanol / Water System
In the case of the (RTV /
PVPVA / MeOH / H2O)
solubility boundary is
encountered at about
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Application of the Drying Model to Solvent Selection for the Ritonavir / PVP-VA / Methanol / Water System
Experimentally, the onset
enthalpy peak occurs
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Drying Model with Phase State Calculation as a Risk Assessment Tool for Solvent Selection
Recap of
Spray drying process throughput can be optimized by choosing
a solvent that exhibits optimal process characteristics (low ΔHvap,
high P, low viscosity) and solubility for the API / polymer system
Mixed solvent systems can improve solubility for low organic
solubility APIs, but can also lead to phase separation risks due
to differential drying rates
Kinetic modeling of the drying process allows compositional
trajectories to be assessed, which can then be plotted against a
quaternary phase diagram to identify high risk solvent systems
to avoid during process development
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Jonathan Cape | Lonza Rapid Fire Presentation | 2020
Disclaimer and Forward-looking statements This presentation (“Presentation”) is the property of Lonza AG and its affiliates (“Lonza”) and any unauthorized use or interception of this Presentation is illegal.
The information contained herein are believed to be correct. However, no warranty is made, either expressed or implied, regarding its accuracy or the results to be obtained from the use of such information. Lonza disclaims any liability for the use of this presentation and the use of the information contained herein is at your own risk. All trademarks belong to Lonza or its affiliates or to their respective third party owners and are only being used for informational purposes. All copyrighted material has been reproduced with permission
from their respective owners, all other materials ©2020 Lonza. All rights reserved. Certain matters discussed in this Presentation may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd., although Lonza Group Ltd. can give no assurance that these expectations and estimates will be achieved. Investors are cautioned that all forward-looking statements involve risks and uncertainty and are qualified in their entirety. The actual results may differ materially in the future from the forward-looking statements included in this Presentation due to
various factors. Furthermore, except as otherwise required by law, Lonza Group Ltd. disclaims any intention or obligation to update the statements contained in this Presentation.
www.pharma.lonza.com Contact Us - click here