integrated chemical product-process design: cape ......integrated chemical product-process design:...

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?



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?


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?



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


Overview of Presentation

• Different types of design problems

• Challenges & opportunities

• Issues & Needs

• Framework for an integrated approach

• Conclusions


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



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, ….



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


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



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?



A. S. Hussain, CDER, FDA, 2002

Process Analytical Technology – PAT

To ensure final product quality!

Estimate critical scientific & regulatory parameters early!



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)


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


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 )


Schematic representation of ice cream structure

Air bubbles

Structured 3D fat network

Ice crystals

Sugar matrix

M. Meeuse, Unilever, 2005



• 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)



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


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


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


Challenges and Opportunities – 2b


,/

,

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


Challenges and Opportunities – 2c


Emulsification-solvent evaporation methodAI loading in polymer


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


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


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


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


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


Issues & Needs - 2

Tools to handle scales & complexityNeeded: methods & tools for development of models

hwax

hcuticle


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


Framework for Integrated Approach - 1

Integration of Product-Product Design

hwax

hcuticle


Framework for Integrated Approach-2a

Types of Models & their Connection


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


Framework for Integrated Approach-3



Available methods & tools



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


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


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

integrated chemical product-process design: cape ......integrated chemical product-process design:...

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