Unit 7 - Process Analytical Technology

Question 1

What is process analytical technology?

Answer 1

A system for designing, analysing and controlling in-line manufacturing process through timely measurements with good quality and performance. The goal is to ensure final product quality.

Question 2

How can PAT reduce waste?

Answer 2

By monitoring the quality along the process rather than just at the end, whole batches do not have to go to waste.

Question 3

How can PAT improve atom economy?

Answer 3

It can prevent unreacted materials as impurities.

It can maximise the yield to get the most out of each reactant.

It can end the reaction when the reactants are used up and the product is at a maximum yield to prevent degradation and unwanted materials lowering yield.

Question 4

How can PAT improve energy efficiency?

Answer 4

It can be determined when the process is finished which means that heating, agitation and other processes can be turned off.

Question 5

How can PAT reduce pollutants emitted?

Answer 5

The pollutants can be detected and then measures can be made to stop them being emitted into the atmosphere.

Question 6

What is quality by design?

Answer 6

A framework concerning designing and developing processes that can consistently ensure a predefined quality, resulting in a real time release of products.

Question 7

What are examples of univariate sensors?

Answer 7

Temperature, pressure, flow, density, pH, colour, turbidity, moisture etc.

Question 8

What are examples of multivariate analysers?

Answer 8

Spectroscopy based: UV-VIS, IR, NIR, Raman, NMR

Separations based: Mass spec, GC, HPLC

Question 9

What are some considerations for process measurement?

Answer 9

The measurement needs to be made in the time scale of a process change.

Positioning is important - the further back in the process, the better.

Question 10

How can spectroscopy give both qualitative and quantitative data?

Answer 10

It can identify what molecules are present (the wavelength which is absorbed).

It can identify how much of each molecule is present (the intensity on the y-axis).

Question 11

What are the benefits of using spectroscopy?

Answer 11

Rapid

Non-invasive and remote.

Lots of information is collected.

Provides information for: identification, quantitative analysis, structural information such as form and crystallinity.

Question 12

Why is ATR a good tool for PAT?

Answer 12

It doesn’t matter how much water is in the solution.

Question 13

What are the advantages of using Mid-Infrared spectroscopy?

Answer 13

The spectrum is highly structured and visually characteristic of material.

The spectrum reflects composition and material properties.

High information content.

Good for all sample types (solid, liquid and gas).

Question 14

What is a case study for the use of FTIR?

Answer 14

Determining the end of reaction for the hydrogenation of nitrobenzene.

Question 15

What are the disadvantages of using mid-infrared spectroscopy?

Answer 15

Sampling can be difficult, especially for solids.

Trace measurements in aqueous media can be difficult.

Problems with windows and transfer optics.

Question 16

What causes absorptions in the NIR region?

Answer 16

Fundamental vibrations through overtones and combinations.

Question 17

What are overtones?

Answer 17

They can be thought of as harmonics. This means a series of absorptions at integer multiples of the frequency.

They are 10-1000 times weaker than the normal absorptions which makes them easier to measure with longer pathlengths.

Question 18

What are combinations?

Answer 18

Combinations arise from the sharing of NIR energy between two or more fundamental absorptions.

Question 19

What do NIR spectra look like?

Answer 19

A small number of broad peaks.

Question 20

What are the advantages of using NIR spectroscopy?

Answer 20

It offers non-destructive uninterrupted sampling.

No sample preparation is required.

Results in seconds.

Multi-component analysis is possible.

It can be used online, inline or at-line.

Question 21

What are the disadvantages in using NIR spectroscopy?

Answer 21

The spectrum is poorly structured and generally difficult for detailed visual characterisation.

Not suitable for gases.

Limited mainly to OH, NH and CH vibrations.

Question 22

What is a case study where NIR was used?

Answer 22

Problem: A pharmaceutical company doubted the coating of the tablet and the API content variability is larger than expected.

Solution: NIR spectrometer used to perform simultaneous reflection and transmission spectroscopy to assess the tablet coating consistency (reflection) and the API content uniformity (transmission).

Question 23

What is the difference in data between IR and Raman spectroscopy?

Answer 23

They have different selection rules.

Symmetric modes are strong in Raman. Asymmetric modes are strong in IR.

Raman is less sensitive to water than IR or NIR so Raman is better when probing aqueous solutions.

Question 24

What is a disadvantage of using Raman spectroscopy?

Answer 24

If the molecule fluoresces, this interferes with the results. This is because Raman has a very weak effect.

Not as much functional group information as mid-IR.

Question 25

What are the advantages of using Raman spectroscopy?

Answer 25

The spectrum is highly structured and characteristic of material.

Spectrum reflects material properties and composition.

High information content - includes both quantitative and qualitative data.

Good for all sample types - aqueous, solid, liquid, gases and slurries.

Question 26

What did the FDA do in 2004?

Answer 26

Shifted their framework from testing quality after the drug was produced to building in quality checks throughout the production process.

Question 27

How can Raman be used in monitoring the quality in bio-pharmaceuticals?

Answer 27

Raman spectra can be taken and this can be converted to a concentration using a calibration curve. This can be used to assess the quality of the product.

Raman spectroscopy is used as it is in situ, non-destructive, rapid and used for lots of different sample types.