Process Engineering

Question 1

Powders are employed in many pharmaceutical processes.

Answer 1

more difficult to handle and process than liquids and gases (flow properties).•granulationand fluidization, facilitate powder transport and feeding.
• particles of a powder pack together to form a bed
•Unlike fluids, it varies greatly with the size, distribution, and shape of the particles .affect
packing and the fraction of the bed that is void.
•Vibration and tapping, which cause rearrangement of the particles and a decrease in the void fraction, increase the bulk density.
•In several processes, these factors are important because the powder is subdivided and measured by volume. Variation of bulk density then causes variation in weight and dose.The variation in the weight of compressed tablets is an excellent example

Question 2

Particle’s properties•Properties dictated by the method of manufacture include:

Answer 2

particle size and distribution,shape,specific surface area,true density,Meltingpoint, and polymorphic form

Question 3

Granulation is a term given to a number of processes used to

Answer 3

produce materials in the form of coarse particles.•In pharmacy, it is closely associated with the preparation of compressed tablets. •Ideally, granulation yields coarse isodiametric particles with a very narrow size distribution.

Question 4

Granulation •Advantages:

Answer 4

Granules flow well. They will feed evenly from chutes and hoppers and will pack into small volumes without great variation of weight.
Segregationin a mixture of powders is prevented if the mixture of powders is granulated.
Each granule contains the correct proportions of the componentsso that segregation of granules cannot cause inhomogeneity in the mixture.
hazards of dust are eliminated, and granules are less susceptible to lumping and caking.
, granular materials fluidize well and a material may be granulated to gain the advantages of this process.

Question 5

Filtration•The applications of filtration are diverse. They may, however, be classified as

Answer 5

either clarification or cake filtration.

Question 6

•Cake Filtration:

Answer 6

filtration of slurries containing a relatively large amount of suspended solids, usually in the region of 3% to 20%.

Question 7

Clarification Filtration

Answer 7

: This term is applied when solid present in liquid is very small and they do not exceed 1.0% and filtrate is the required product.

Question 8

Control of exothermic reactions…

Answer 8

Slow or portionwiseaddition
•Continuous monitoring in-line or out of process
•Stop reagent addition
•Decrease jacket temperature
•Dilute the reaction mixture
•Stop stirring (if biphasic system)
•Dump reactor contents into ice / water
•Crash cool –add ice

Question 9

Exothermic Reactions

significant hazard on scale-up

Answer 9

•The challenge is to maintain a constant temperature•Avoid reagent accumulation–Vigorous mixing–Higher temperature –refluxing–Dissolve solids first giving controlled addition•Best way is to know and control the rate of reaction

Question 10

HEATING AND COOLING BECOME MUCH SLOWER WITH INCREASED

Answer 10

VESSEL SIZE –The bigger the scale, the harder it is to cool!

Question 11

Differential Scanning Calorimetry (DSC)

Answer 11

Thermoanalyticaltechnique•Measures the difference in heat flow between a sample and a reference•the difference in the amount of heat required to increase the temperature of a sample and reference is measured as a function of temperature.•Both the sample and reference are maintained at nearly the same temperature throughout the experiment

Question 12

Control loupes in DSC

Answer 12

Average Temperature control Loop : Gives predetermined rate of temperature increase or decrease
Differential temperature control loop : Maintain temperature of the two pan holders always identical

Question 13

Differential Scanning Calorimetry (DSC) Advantages

Answer 13

1.Rapidity of the determination2.Small sample masses3.Versatility4.Simplicity 5.Applicable6.Study many types of chemical reactions7.No need of calibration over the entire temperature

Question 14

HAZOP –Hazard and Operability study

Answer 14

Systematic stepwise study through the process as written using key-word logic

Question 15

Safety:

Answer 15

•First to personnel•Second to plant•Third to environment•Fourth to product

Question 16

•HSE –Remove, minimise, mitigate _______

Answer 16

hazards

Question 17

•HSNO –Specific engineering design and management ________

Answer 17

processes

Question 18

Validation is defined as:

Answer 18

“ A documented program that provides a high degree of assurancethat a specific process, method or system will consistentlyproduce a result meeting pre-determinedacceptance criteria”

Question 19

Validation is Performed by _____personnel following ________ protocols

Answer 19

trained

pre approved

Question 20

The company’s overall policy, intentions and approach to validation including validation of production processes, cleaning procedures, analytical methods, computerized systems and persons responsible for design, review approval and documentation of each validation phase, should be ________
•The above requirement is usually met through creation of a _____________

Answer 20

documented

Validation Master Plan (VMP)

Question 21

Validation Requires the _______of critical parameters/attributes and associated ranges necessary for reproducible operation•Identify process _________ that could affect the critical quality attributes of the API
•Determine the _____of each critical process parameter expected to be used during routine manufacturing and process control

Answer 21

identification
parameters
range