Transport Phenomena

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hefsira@post.jce.ac.il

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Typical Pharmaceutical Process

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(API ( -

100.8%-

(. )

750- .

-1'

2'

3'

-4'

PABA 5'

PABA 6'

Sulfanilamide -7'

Sulfacetamide -8'

-9'

10'

3

4

/

.

/

!!!, ,

MSDS

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MSDS

A Material Safety Data Sheet (MSDS) provides basic information on a material or chemical product. A MSDS describes the properties and potential hazards of the material, how to use it safely, and what to do in an emergency.

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Reading the MSDS

Introduction

1. Product and Company Identification

2. Hazards Identification3. Composition, Information on Ingredients

4. First Aid Measures

5. Fire Fighting Measures

6. Accidental Release Measures

7. Handling And Storage

8. Exposure Controls, Personal Protection9. Physical And Chemical Properties

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10. Stability And Reactivity11. Toxicological Information

12. Ecological Information

13. Disposal Considerations

14. Transport Information

15. Regulatory Information

16. Other Information

Reading the MSDS

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Potential Health Effects

Route of Entry (Primary Routes of Exposure)

The possible routes of exposure are skin contact, eye contact, inhalation (respiratory system),

and ingestion (swallowing).

Includes general information about appropriate personal protective equipment for handling this material

PERSONAL PROTECTIVE EQUIPMENT

It is vital that this information be followed

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Reading the MSDS

MSDS Information:

PHYSICAL DATA

The following information is usually included:

Boiling Point: temperature at which liquid changes to vapor state

Melting Point: temperature at which a solid begins to change to liquid

Vapor Pressure: a measure of how volatile a substance is and how quickly it evaporates

Flash point: the lowest temperature at which a liquid produces enough vapor to ignite.

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PHYSICAL DATA (cont.) Vapor Density (air=1): weight of a gas or vapor

compared to weight of an equal volume of air

Specific Gravity (water=1): ratio of volume weight of material to equal volume weight of water

Solubility in Water: percentage of material that will dissolve in water, usually at ambient temperature

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PHYSICAL DATA (cont.)

Appearance/Odor: color, physical state at room temperature, size of particles, consistency, odor, as compared to common substances

Odor threshold refers to the concentration required in the air before vapors are detected or recognized

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13

,

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: -1'

-

=VD

,

.

( " " )

,

.

,

,

.

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( )

15

loutoutout

pininin hz

g

VPhz

g

VP

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22

:=g

V

Z

P

hp

hl

:

-

-

-

) , . ( '

fMoody (Moody )

k

16

g

V

D

Lfh MoodyL

2

2

kg

VhL

2

2

Moody

17

DRe,ff

fMoody=4fFanning

V1A1=V2A2

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(manometer) :

(rotameter):

19

: 2' ,

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.

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..(

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Classification of Mixing Processes and Applications

Mixing Equipment

Liquid Mixing Fundamentals

Mixing and Blending in Low Viscosity Liquids

High Viscosity Mixing in Stirred Tanks

Mass Transfer and Mixing

Solid-Liquid Mixing

The term mixing refers to all those operations that tend to reduce non- uniformity in one or more of the properties of a material in bulk

Economic impact of mixing-related problems including scale-up and start up problems, waste material and by-products

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Examples of processes possibly affected by mixing:

Dissolution of an intermediate in a stirred vessel prior to reaction (mass transfer)

Precipitation of API or intermediate (crystallization) Minimization of impurity formation during synthesis of a

drug product (parallel/consecutive homogeneous reaction) Suspension of a catalyst during heterogeneous catalysis

(mass transfer + heterogeneous reaction) Preparation of nano/micro-particles or droplets of desired

particle size distribution (particle size control) Achievement of a uniform temperature in a crystallizer

and temperature control (heat transfer)

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:

,

,

(uniformity)

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Mechanically Stirred Tanks and Reactors

Baffle

Motor

Gearbox

Shaft

Impeller

Stirred Reactors

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D

T

H

Cb

B

T

H

Cb

S23

S12

Tank shape = cylindrical

T = Internal diameter of tank

HT = Internal height of tank

H = Z = Liquid height

B = Baffle width

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Shape of tank bottom (flat, dished, conical, hemispherical)

Baffle length (full, half)

Number of baffles

Baffle position

Gap between baffles and tank (B)

Gap between baffles and tank bottom

Mechanically Stirred Tanks : Other Geometric Characteristics

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Typical Baffle Arrangementin a Stirred Tank

Baffle

,

, ,

. Baffles-

,

. Baffles-

!!!

,

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Examples of Radial Flow Impellers

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Flow Generated by a Radial Impeller in a Stirred Tank

Examples of Axial Flow Impellers

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Flow Generated by an Axial Impeller in a Stirred Tank

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Blending Capabilities of Different Impellers

Impeller Viscosity Range

Open Impellers < 100,000 cP

- Propellers < 200 cP

- Turbines < 5000 cP

- Paddles < 100,000 cP

Anchors < 50,000

Helical Ribbons > 30,000

[Torque [N*m-

P= 2

P is power, is torque and is rotational speed

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Small scale- ,

Large scale-

)

(:

34

,

,

: 3'

' .

. ,

( ) -

( ) -

: -4'

. -

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PABA :4-Aminobenzoic acid 5'

TLC

Thin-layer chromatography

PABA 6'

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Sulfanilamide -7'

Sulfacetamide -8'

-9'

10'

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Heat Transfer experiments

Process Safety

If the process cant be run safely, it shouldnt be run at all

Reminder of theory

Small scale -> Production scale

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Heat Transfer Evaluation

Safety: Management of Runaway Scenario

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Exothermicity in the pharmaceutical Industry

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Overall Heat Transfer Coefficient

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RC1 Reaction Calorimeter

Measuring heat profiles under process-like conditions

Allows optimize processes under safe conditions while determining all critical parameters and reducing the risk of failure on a large scale

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Calorimetry Experiment

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Reminder of U overall heat transfer coefficient

U is a function of various parameters

the reaction mixture viscosity, stirring speed, cp of fluid in the vessel etc.

The vessel (k conductivity and thickness)

External jacket heat transfer

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Film Theory

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Reminder of U overall heat transfer coefficient

Difficulties:

Since U is dependent on both the process and the reactor

Time consuming

Procedure:

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Scale Up of heat transfer characteristics

Determination of U - Wilson Plot

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hr scale up

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The lab experiment

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Output

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Date Time T_REACTOR T_JACET_IN T_JACET_OUT

Instant Instant Instant

C C C

09/09/2013 09:31:35 23.3 24.3 23.9

09/09/2013 09:32:35 23.3 24.3 23.9

09/09/2013 09:33:35 23.3 24.4 23.4

09/09/2013 09:34:35 23.3 29.8 26.5

09/09/2013 09:35:35 23.6 35.7 31.7

09/09/2013 09:36:35 24.3 38.7 36.5

09/09/2013 09:37:35 25.3 39.9 37.8

09/09/2013 09:38:35 26.4 39.9 38.3

09/09/2013 09:39:35 27.3 39.7 38.4

09/09/2013 09:40:35 28.1 39.6 38.3

09/09/2013 09:41:35 28.9 39.5 38.3

09/09/2013 09:42:35 29.6 39.5 38.4

09/09/2013 09:43:35 30.1 39.5 38.5

09/09/2013 09:44:35 30.7 39.6 38.6

09/09/2013 09:45:35 31.3 39.6 38.6

09/09/2013 09:46:35 31.8 39.6 38.6

09/09/2013 09:47:35 32.3 39.6 38.6

09/09/2013 09:48:35 32.8 39.6 38.7

09/09/2013 09:49:35 33.2 39.6 38.7

Reactor with Steam Condenser

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1.

.

. 5

. 9

. 10

reflux . 12

. 13

. 14

. 15

. 18

. 20

,THF

,

.

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