Post on 04-Sep-2021
Integrated Chemical Product-Process Design: CAPE Perspectives
Rafiqul GaniCAPEC
Department of Chemical EngineeringTechnical University of Denmark
DK-2800 Lyngby, Denmark
Integrated Chemical Product-Process Design: CAPE Perspectives 2
IntroductionProblem Definition
Process Design Product Design
Products
Equipment parameters?
Product molecule/ mixture?
Product properties
Product functions?
Molecule or mixture synthesis?
Applicationprocess?
Performance
Product Application Design
Integrate Process-Product& Application
Atoms or molecules
Raw material Process
Flowsheet?Operating condition?
Product
Application conditions?
Equipment parameters?
Integrated Chemical Product-Process Design: CAPE Perspectives 3
IntroductionExamples of Product-Process Integration
Process Design Product Design
Atoms or molecules
Raw material Process
Flowsheet?Products
Product properties Product
molecule/ mixture?
Operating condition?
Equipment parameters? Product
functions?Molecule or mixture synthesis?
•Petroleum blends & petroleum products
•Polymers & blends
•Specialty chemicals (including drugs, ….)
Routinely solved!
Can be solved!
Process role?
Integrated Chemical Product-Process Design: CAPE Perspectives 4
IntroductionExamples of Product-Process Integration
Product molecule/ mixture?
Product properties
Product functions?
Performance
Product Application Design
For products such as drugs, pesticides, food, …delivery and application is important & needs to be validated
Product Design
Atoms or molecules
Molecule or mixture synthesis?
Product Applicationprocess? Production process
needs to be reliable – first time right is important
Application conditions?
Equipment parameters?
Integrated Chemical Product-Process Design: CAPE Perspectives 5
IntroductionCurrent Status
Active ingredients; additives, …
Reactive agents, solvents, process fluids, ….Consumer products
Product type
Operationally reliableEconomically efficientProcess design
Chemicals & chemical productsProduct-Process Characteristics
Difficult to validateEasy to validateApplication process
High-valueLow-value
• CAPE/PSE have routinely solved integrated product-process design problems for low value chemical products
• CAPE/PSE is very well equipped to solve the integrated product-process design problems for high value chemical products
Integrated Chemical Product-Process Design: CAPE Perspectives 6
Overview of Presentation
• Different types of design problems
• Challenges & opportunities
• Issues & Needs
• Framework for an integrated approach
• Conclusions
Integrated Chemical Product-Process Design: CAPE Perspectives 7
Different Product Design Problems1. Design of Molecule and/or Mixture
Given, a set of target properties θ, find molecules or mixtures that match the target properties CAMD & CAMbD
solvents, fluids, …
High
drugs, pesticides, aroma, ….
Low ValueLarge Production rate SmallEasy Finding candidates Difficult
Integrated Chemical Product-Process Design: CAPE Perspectives 8
Different Product Design Problems1. Design of Molecule and/or Mixture
CAMD & CAMbD: ExampleFrom a list of 250 solvents, find those that can be used as an oil-paint additive characterized by 25%-, 50%- & 75%-evaporation rate, solubility, viscosity and surface tension. Form the feasible set, find the optimal cost solvent mixture.
• Synthesis method for mixtures• Property models for solvents• Evaporation models for solvents• Cost = f(Ci, xi)
Note: Mixture design similar to oil-blend (petroleum, edible oil, ….), polymer blend, formulations, ….
Integrated Chemical Product-Process Design: CAPE Perspectives 9
Different Product Design Problems1. Design of Molecule and/or Mixture
Given, a set of target properties θ, find molecules or mixtures that match the target properties CAMD & CAMbD
drugs, pesticides, aroma, ….
Issues & Needs
solvents, fluids, …
• Generate feasible candidates (synthesis method & tool)• Estimate target properties (predictive property models)• Evaluate performance (application process models)
Achenie et al, Computer Aided Molecular Design: Theory & Practice, CACE-12, 2003
Integrated Chemical Product-Process Design: CAPE Perspectives 10
Different Product Design Problems2. Product-Process Evaluation
Given, a list of feasible candidates (product and/or process), the objective is to identify/select the most appropriate product-process based on a set of performance criteria.
For product design, this problem is similar to CAMD but without the generation step; also, similar to CAMbD where additives are added to a product to significantly enhance the performance of the product
Examples• Select the optimal combination of pesticide and
surfactants that match the needs of specific plants• Select the optimal combination of drug/pesticide,
solvent and polymeric microcapsule for controlled release of the product
• Increase the yield of a product by hybrid process operation
Integrated Chemical Product-Process Design: CAPE Perspectives 11
Different Product Design Problems2. Product-Process Evaluation
Simple Example: From the derivatives of Barbituric acid, identify the candidate that is required in the smallest amount (C) to produce a 1:1 complex with protein (binding to bovine serum albumin) –calculated as a function of octanol-water partition coefficient of the candidate compounds: Log10(1/C) = 0.58 log10P + 0.239
• Synthesis tool for isomer generation• Property model for Log10P• Verify solubility in water
Note: How is the backbone (barbituric acid) identified and how is the relation (drug activity) between C vs log10P found?
Integrated Chemical Product-Process Design: CAPE Perspectives 12
Different Product Design Problems2. Product-Process Evaluation
A. S. Hussain, CDER, FDA, 2002
Process Analytical Technology – PAT
To ensure final product quality!
Estimate critical scientific & regulatory parameters early!
Integrated Chemical Product-Process Design: CAPE Perspectives 13
Different Product Design Problems2. Product-Process Evaluation
Process Analytical Technology – PAT
To ensure final product quality!
Estimate critical scientific & regulatory parameters early!
Tablet Manufacturing (D. Radspinner, 2004)
Tablet Manufacturing (D. Radspinner, Sanofi-Aventis, 2004)
Integrated Chemical Product-Process Design: CAPE Perspectives 14
Different Product Design Problems3. Design of Product-centric Process
Problem Characteristics• Products are consumer
products such as soap, detergents, fragrances, food, skin-care …
• Complex chemical systems involved
• Life of the product is getting shorter
• Volume/cost relationship needs to be improved by selling more
• Low-cost chemical routes are needed (better catalysts, faster reactions, increased yields, …)
Issues & Needs
Algorithm for generation of process flowsheet or batch recipe
Process-operation models for verification by simulation
Property models for product/process analysis
Integrated Chemical Product-Process Design: CAPE Perspectives 15
Challenges and Opportunities - 1
Process for Ice Cream Manufacture - Unilever
Product properties:Consists of air-bubble, fat, water crystals in a sugar matrixTexture is function of the sizes of air-bubble, fat droplet & water crystal
Process properties:Contains batch & continuous operational stepsSame production-line may produce other productsCleaned every dayLarge scale production with accurate control of product texture
M. Meeuse, Unilever, 2005 (see also, paper in the ESCAPE-15 proceedings, 2005 )
Integrated Chemical Product-Process Design: CAPE Perspectives 16
Schematic representation of ice cream structure
Air bubbles
Structured 3D fat network
Ice crystals
Sugar matrix
M. Meeuse, Unilever, 2005
Integrated Chemical Product-Process Design: CAPE Perspectives 17
Different Product Design Problems3. Design of Product-centric Process
• 14 million molecular compounds have been synthesized
• About 100 thousand can be found in the market
• Only a small fraction can be found in nature
• Most of them will need to be conceived, designed, synthesized & manufactured!
Charpentier, Chem Eng Sci, 2004
Design Problem: Given, the identity of a product & its quality needs, raw materials that could be used, determine the process that can produce it (reliably, efficiently and sustainably)
Integrated Chemical Product-Process Design: CAPE Perspectives 18
Different Product Design Problems3. Design of Product-centric Process
Example: Manufacture of Carnosic acid by recovering it from popular herbs (Harjo et al 2004)
FeedPreparation
ProductRecovery
ProductPurification
Harvested Plants
WashingAgent
Moisture,Contaminants,Unused Parts
Impurities,ByProducts/
Products
Residues,ByProducts/
Products
Solvent/MSA
Additives
Products
Solvent/MSA
Products
ProductFinishing
Products/Byproducts
Products/Byproducts
Remaining Solvent/MSA
Acetone
Na2CO3 (aq)
Dry1 Cut
Residue
Washedrosemary leaves
H2SO4 (aq)
H2O,Acetone,
Volatile impuritiesWater-insolubleimpurities (solids)
H2O,Water-soluble impurities
Na2SO4
Acetone,H2O
Carnosic acid
Moisture
RemainingMSA
Cry1 F1 S1
S2
Extr
F2
Dry2
H2O
Cry2
Extract
H2O
Integrated Chemical Product-Process Design: CAPE Perspectives 19
Challenges & OpportunitiesProduct-centric Process Development*
• The key to success is first identify the desired end-use properties of a product and then to control product quality by controlling the microstructure formation
• Different scales of size, time & complexity
• Collect sufficient data to enable systematic study leading to the development of appropriate mathematical models
Charpentier, Chem Eng Sci, 2004* Considering structured products
Integrated Chemical Product-Process Design: CAPE Perspectives 20
Challenges and Opportunities – 2a
Polymer Based Microcapsules
Multicomponentsystems consisting ofpolymer (P) Active ingredient (AI)surfactant (M) and solvents (S).
AI loading in polymer
• Suitability and optimal concentrations of raw materials•Polymer screening
•Solvent selection
•Process design•Optimization of operating T
•Design of sustain-release capabilities
G. Tse et al., J. Controlled Release, 1999
Integrated Chemical Product-Process Design: CAPE Perspectives 21
Challenges and Opportunities – 2b
Polymer Based Microcapsules
,/
,
iA jA A
i j jA Ai
xKx
γγ
∞
∞= ≈
,AP∞
,Awγ∞
,AMγ∞
1
1(1 ( 1))
F
iF l il il
y K zβ−
=
+ − =∑
11
1
10, 1,2,.. 1
1 ( 1)
Cij
i Fi
l ill
Kz j F
Kβ−
=
=
−= = −
+ −∑
∑J. Abildskov & I. Kouskoumvekaki, PEC05-41, 2005
• Polymer phase (P+S+AI):GC-FLORY • Aqueous phase (W+AI): UNIFAC • Micelle phase (M+AI): GC-FLORY
• Equilibrium factors:
• Material balance:
• Mol fractions:
γ
AI loading in polymer
Integrated Chemical Product-Process Design: CAPE Perspectives 22
Challenges and Opportunities – 2c
Polymer Based Microcapsules
Emulsification-solvent evaporation methodAI loading in polymer
Integrated Chemical Product-Process Design: CAPE Perspectives 23
Challenges and Opportunities - 3Controlled release through Microcapsules
Releasemedium
ro
ri
CrCd
CoreMembrane
Toxic concentration
Min. Eff. concentration
Under dosing
Time
Con
cent
ratio
n in
env
ironm
ent
Min. Eff.
Overdosing
Under dosing
Definition of microcapsule:
Core: AI solid/liquid, pure/solution (or dispersion) + additives (solvent, emulsifier,...)
Coating: polymer membrane (rate-controlling) porous/non-porous
Release mediumTime course of concentration from conventional application () Controlled releaseapplication (--)
Km-d , Km-r , D
Integrated Chemical Product-Process Design: CAPE Perspectives 24
Challenges and Opportunities – 4a
Pesticide Uptake in a Leaf
C14
C15
C16
C17
Wax
Cuticle
Plant Compartment containing epidermis and the layers beneath.
hwax
hcuticle
CuticleEpidermis
Multilayer Multilayer Uptake ModelUptake Model
DropletVd
r(t>0) r(t=0)
Energy Contribution
Droplet Evaporation Model
Internal Structure of Leaf
Integrated Chemical Product-Process Design: CAPE Perspectives 25
Challenges and Opportunities – 4b
Pesticide Uptake in a LeafDiagrammatic representation of Equations used for Active Ingredient & Surfactant in the Model
* *( 1- 0) *AI AI AIdM D S C C dCdVddt hwax dt
−= +
( )1000* * * *
*ad j adj water adj adjAI
AI adj
MW S S dCd dMdCd Vddt MW Vd dt dtρ
− = +
21
1 ( * / )*( 2 2 1 0)AI waxdC D B h C C Cdt
= − +
Droplet
hwax
Plus Surfactant Equations
1 21 2 1 0( * / )*( 2* )adj
adj wax adj adj adj
dCD B h C C C
dt= − +
Plus SurfactantEquations
0
Layers
0CO=KwdAI*CdAI
Wax1
216 15
16 (( * / )*( 17 16)) (( * / * )*(( * 16) 15))AI cut AI wax cutdC D B h C C D B h h KwcAI C Cdt
= − − −
217
17 ( * / )*( 18 2* 17 16)AI cutdC D B h C C Cdt
= − +Plus SurfactantEquations
15Plus SurfactantEquations
16hcut
Cuticle17
30Plus Surfactant EquationsCpAI=C30/KcpAI Plant
Integrated Chemical Product-Process Design: CAPE Perspectives 26
Challenges and Opportunities - 5
Feed Retentate
Permeate
GIVEN: Target properties of polymer
TARGET:Find feasible alternative
structures of polymer thatfulfill ’Target’ properties
Find a suitable polymer
GIVEN:Mixture and desireddegree of separation
TARGET:Design the separation
Design of Membrane BasedSeparation ProcessDesign of Polymer
Polymeric-membrane based gas separation
Simultaneous design of polymer & separation process
Integrated Chemical Product-Process Design: CAPE Perspectives 27
Issues & Needs -1
Tools to handle scales & complexity
hwax
hcuticle
Polymerization of olefins on supported catalysts – consider different length scales
Charpentier, Chem Eng Sci, 2004
Problems highlighted under challenges & opportunities can be solved if the necessary methods & tools are available
Integrated Chemical Product-Process Design: CAPE Perspectives 28
Issues & Needs - 2
Tools to handle scales & complexityNeeded: methods & tools for development of models
hwax
hcuticle
Integrated Chemical Product-Process Design: CAPE Perspectives 29
Issues & Needs - 3
The need for integration
hwax
hcuticle
• Provide capability to create & manipulate product-process models
• Provide simulation techniques & supporting processing techniques to allow simulations of product and process performance
• Provide capability to simulate & evaluate many design alternatives in parallel to fast trade-off evaluations
• Provide integrated plug & play toolset for modelling and simulation of life-cycle factors for generic products
IMTI, Report, 2000
Integrated Chemical Product-Process Design: CAPE Perspectives 30
Framework for Integrated Approach - 1
Integration of Product-Product Design
hwax
hcuticle
Integrated Chemical Product-Process Design: CAPE Perspectives 31
Framework for Integrated Approach-2a
Types of Models & their Connection
Integrated Chemical Product-Process Design: CAPE Perspectives 32
Framework for Integrated Approach-2b
Types of Models & their Connection
Oslo Evaporative Crystallizer (process model)
Solubility versus temperature (constitutive model)
Integration of process model with various constitutive models gives us a model of wide application range
Integrated Chemical Product-Process Design: CAPE Perspectives 33
Framework for Integrated Approach-3
Integrated Chemical Product-Process Design: CAPE Perspectives 34
Framework for Integrated Approach-4
Available methods & tools
Integrated Chemical Product-Process Design: CAPE Perspectives 35
Framework for Integrated Approach-5
Simultaneous product-process
design
Loic d’Anterroches, 2005
Group contribution approach for synthesis/design of molecules as well as process flowsheets
Atomic-groups are used to design molecules while process-groups are used to design flowsheets
Integrated Chemical Product-Process Design: CAPE Perspectives 36
Conclusions & Future Work
• For CAPE/PSE methods to work, models are necessary– If appropriate models are available, almost all
problems can be solved• CAPE/PSE have solved product-process
problems involving low-value simple chemical products
• High-value chemical products or product centric process design problems involve complex chemical systems– The limiting factors for these problems are availability
of data and appropriate models
Integrated Chemical Product-Process Design: CAPE Perspectives 37
Acknowledgements
• Dr. M. Pinsky, Firmenich, Swiss-USA• Dr. M. Meeuse, Unilever, The Netherlands• Dr. G. Bell & Dr. I. Shirley, Syngenta, UK• Dr. P. M. Harper & Dr. M. Hostrup, CapSolva, Denmark• CAPEC industrial consortium member companies• Lektor Jens Abildskov, CAPEC-KT, DTU• Dr. I. Kouskoumvekaki, CAPEC-KT, DTU• PhD-students (L. d’Anterroches, M. Sales-Cruz, N. Muro-
Sune, V. Soni, P. T. Mitkowski)• Mr. Ahsan Munir, MSc-student• Prof. J. C. Charpentier (Chem Eng Sci, 59, 1617-1640, 2004)• Prof. Ka Ng (ChERD, 82(A11), 1494-1504, 2004) • IMBT (First product correct: Visions & goals for the 21st
century manufacturing enterprise, Integrated Manufacturing Technology Initiative, Report, 2000, USA