FAIRSpectra - Enabling the FAIRification of Spectroscopy and Spectrometry
Operations extraction-ppt-final
1. Operations: Drug Extraction
GROUP 2- UNIT #6
MEMBERS
ETHAN GAYLE
SUE LINTON
KRYSTAL LINDO
DANIELLE HENRY
JANELLE WALLACE
SHANIANN
RAHEEM STEPHENS
2. Objectives
Define terminologies of interest.
Discuss the principles behind the drug extraction process.
Examine the production technology and mechanistic modeling of the drug extraction process.
Discuss the optimization of the drug extraction production process.
Evaluate the basic equipment for laboratory scale.
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3. Terminolgies / Acronyms
EXTRACT
A concentrated preparation of a drug obtained by removing the active constituents of the drug
with suitable solvents, evaporating all or nearly all of the solvent, and adjusting the residual mass
or powder to the prescribed standard.[1]
EXTRACTION
The separation of medicinally active portions of animal or plant tissues from the inactive
components through the use of selective solvents.[2]
DRUG EXTRACTION PRODUCTION PROCESS (DEPP)
The DEPP is one wherein a solvent or chemical reagent that offers high solubility for the effective
constituent (EC) in the herbs and poor solubility for constituents that need not be extracted is
applied to solid herbs and used to isolate the EC from medicinal plants.[3]
[1] Farlex, (2012). Farlex Medical Dictionary: “Extract”. Retrieved from: https://medical-dictionary.thefreedictionary.com/extracts
[2] Mudassar, A. (2015). Health and Medicine. Extraction in Pharmaceutics.
[3] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
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4. Terminolgies / Acronyms (Cont’d)
EFFECTIVE CONSTITUENT (EC)
Refers to the active chemicals or compounds that possess a desired or medicinal
effect of interest . [1]
SOLVENT
A substance (solid, liquid or gas) that dissolves a solute (a chemically different liquid,
solid or gas), resulting in a solution. [2]
MARC
An insoluble residue(skins, pips or seeds) remaining after extraction of a solution (as a
drug) with a solvent.[3]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
[2] Ahmad, Z. (2013). Health and Medicine: Solvents Used in Pharmacy.
[3] Merriam-Webster. (n.d.). Marc. In Merriam-Webster.com dictionary. Retrieved from: https://www.merriam-webster.com/dictionary/marc
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5. Terminolgies / Acronyms (Cont’d)
SOLUBILITY
The maximum concentration of a substance that may be completely dissolved in a
given solvent at a given temperature and pressure. [1]
[1] GONG Y., GRANT D.J., BRITTAIN H.G. (2007) Principles of Solubility. In: Augustijns P., Brewster M.E. (eds) Solvent Systems and Their Selection in Pharmaceutics and
Biopharmaceutics. Biotechnology: Pharmaceutical Aspects, vol VI. Springer, New York, NY
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6. The Drug Extraction Process
Drug extraction or leaching is the basic and primary process of drug production used to isolate
the effective constituent (EC) from medicinal plants.
In DEPP a chemical reagent is utilized in which the EC is highly soluble, however the other
constituents are poorly soluble and is applied to the herbs
The EC is dissolved out of the herb into the solvent/reagent and the EC can be extracted to be
used in forms of drugs.[1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
6
7. The Drug Extraction Process (Cont’d)
The process is based primarily on:
1. Mathematical model of drug extraction tank
2. Mass transfer model of effective constituents (EC)
3. Mechanistic modeling of volatile oil recycling
4. Efficiency model of the oil-water separator[1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
7
8. The Drug Extraction Process (Cont’d)
It is assumed that:
After crushing the herb particle is spherical
The effective constituent of the herb has been uniformly dispersed in the solvent
due to stirring
The EC in the outer layer is the first to be dispersed to the solvent followed by the
EC in the inner layer which first goes to the outer layer then the solvent.[1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
8
9. The Drug Extraction Process (Cont’d)
The efficiencies of the EC and volatile oil are the main quality indicators of the
drug extraction production process (DEPP).
Factors influencing these indicators include:
1. Radius of herb particles
2. Extraction temperature
3. Extraction time
4. Concentration difference
5. Solid-liquid contact condition[1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
9
10. AQUEOUS TWO-PHASE EXTRACTION
(ATPE)
This is a liquid-liquid fractionation technique used for the extraction, purification,
separation of proteins, enzymes and other biomolecules from plant and animal
sources.
The ATPE systems are made by mixing a variety of components in water (main
component of both phases)
Water then forms a gentle environment for biomolecules to separate and polymers to
stabilize their structure.
The system may be formed by: two polymers, Polyethylene Glycol (PEG) or a
polymer and salt (Phosphate or citrate), Ionic and/or non-ionic surfactants [1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
10
11. LIQUID-LIQUID EXTRACTION
Also known as “Solvent Extraction” or “Partitioning”.
Involves the separation of compounds according to their relative solubilities in
immiscible liquids (usually polar vs non-polar/organic)., which are separated with a
separatory funnel or separation tanks. [1]
Sufficient contact time for the mixing of liquids is
crucial in this process.
In industrial settings, centrifugal extractors are used followed
by rapid separation
[1] Berk, Z. (2018). Food Processes Engineering and Technology. Extraction: Liquid-Liquid Extraction. 3rd Edition. pp 237-238
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12. SOLID-LIQUID EXTRACTION
Also known as “Leaching”
Involves the separation of components based on the preferential dissolution of one or more of the
components of a solid mixture in a liquid solvent.[1]
Dried materials are normally powdered before extraction whereas fresh plants are macerated
(softened) with a suitable solvent.
Process is similar to liquid-liquid extraction, except that the solute is dispersed in a solid matrix,
rather than in a carrier liquid.
[1] Deiner, J. (n.d.). Jove:’Solid-Liquid Extraction’. Retrieved from: https://www.jove.com/science-education/5538/solid-liquid-extraction
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13. HEAT & MASS TRANSFER OF EFFECTIVE
CONSTITUENT
The principles and computing method follows that of solid-liquid extraction (i.e solute,
solvent and inert solid)
The herb particles are believed to be made of solute (EC) and inert carriers like the herb
residues.
A gas-liquid film is placed at the interface between the solid particles and the liquid
phase.[1]
[1] Doran, P. (2013). Bioprocess engineering principles (2nd ed.). London: Academic Press.
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14. MASS TRANSFER PROCESS (Cont’d)
Five (5) Main Steps Include:
1. Diffusion of the solvent into the herb particle surface
2. Permeation of the solvent from the herb surface to the interior
3. Dissolution of the EC inside the herb particles
4. Diffusion of EC from inside the herb particles to the surface (internal diffusion)
5. Diffusion of EC from the herb particle surface to the solvent across the gas-liquid
film (external diffusion) [1]
[1] Doran, P. (2013). Bioprocess engineering principles (2nd ed.). London: Academic Press.
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15. EXTRACTION OF VOLATILE OIL
Volatile/ Essential Oils are typically
insoluble in water and this makes it
easier for them to be distilled along with
water vapour. [1]
[1] Doran, P. (2013). Bioprocess engineering principles (2nd ed.). London: Academic Press.
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16. EXTRACTION OF VOLATILE OIL
(Cont’d)
Major steps in process include:
1. Internal diffusion: With an increase in temp,
Volatile oils diffuse into the outer surface of the
solid herb particle from the interior
2. External diffusion: Volatile oils diffuse into the
water vapour from the surface of the solid particle
by threading the gas-liquid film
3. Gas-liquid transition: Volatile oils and water
enter the condenser and are condensed into the
liquid phase after which both are separated
through the oil-water separator[1]
[1] Doran, P. (2013). Bioprocess engineering principles (2nd ed.). London: Academic Press.
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18. Production Technology & Mechanistic
Modeling
Pre-Processing (of Herb Materials)
The herb materials are crushed and soaked in water to inflate the herb organization.
This increases the dissolution and diffusion of the effective constituents (EC) during extraction.
[1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
18
19. Production Technology & Mechanistic
Modeling (Cont’d)
Extraction The pre-processed herb materials are placed in
the extraction tank and steam is added through
the bottom and the sides of the tank.
The temperature is increased and the EC and
the Volatile Oil will diffuse into the extraction
solution and water vapour, respectively.
This is done multiple times to the same batch
of herbs to avoid wastage of raw materials. [1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
19
20. Production Technology & Mechanistic
Modeling (Cont’d)
Separation
The feed liquid containing EC and volatile oil are separated from the herb residues and the
steam respectively using the filter and oil-water separator.
The feed liquid and volatile oil are then sent to the other phase for further processing. [1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
20
22. Optimization of the DEPP
The main aim for optimizing the DEPP is:
to reduce the costs of manufacturing and improve economic benefits while
meeting quality standards.[1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
22
23. Optimization of the DEPP (Cont’d)
More specific goals include:
Pre-processing of Herb Material:
Speed up EC (effective constituent) dissolution and spread during extraction.
Extraction:
Reduce the wastage of raw materials.
Separation:
Improve EC and VO (volatile oils) extraction efficiencies; DEPP's principal consistency
metrics.
To develop a mechanistic model and a predictive model.[1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
23
24. Optimization of the DEPP (Cont’d)
More specific goals (continued):
Predictive Model:
Develop several classical optimization algorithms that are adapted to address the problem of
optimization. Eg. particle swarm optimization (PSO), differential evolution (DE) and artificial bee
colony (ABC).
Mechanistic model:
DEPP is a complex heat and mass transfer device, and its mechanistic model consists mainly of the
following components: Mathematical Drug Extraction Tank Model, EC Mass Transfer Model,
Mechanical VO Recycling Model, and Oil-Water Separator Efficiency Model. [1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
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25. Disadvantages of the DEPP
Drawbacks to the DEPP include:
Low extraction Yields
High energy consumption
Wastage of Materials [1]
[1] He, D., Wang, Z., Yang, L., Liu, T., Yao, Y., & Mao, Z. (2016). Modeling and optimization of the drug extraction production process. Scientific Programming, 3-5.
http://dx.doi.org/10.1155/2016/3279423
25
26. Ultrasound-Assisted Extraction (UAE)
DEFINITION
This is the process of transferring a substance from any matrix to an appropriate
liquid phase, assisted by sound waves (>20 KHz in frequency) that propagate
through the liquid media.[1]
[1] Royal Society of Chemistry, (n.d.). Ultrasound Extraction. Retrieved from: https://www.rsc.org/publishing/journals/prospect/ontology.asp?id=CMO:0001611&MSID=B911696F
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27. Optimizing Multi-Extraction
What is Multi-Extraction?
A multi extraction or multiple extraction involves adding a
suitable solvent to a substance known to contain a desired
analyte in order to extract it and then repeating the procedure
with new solvent each time to increase overall yield of the
analyte from the substance.[1]
[1] Zakaria, A. N. (2015). Extraction methods used in medicinal plants. Retrieved from
https://www.researchgate.net/profile/Arvind_Singh56/post/What_are_the_best_extraction_methods_for_herbal_plants/attachment/5bf2ff2dcfe4a764550348f1/AS%3A69474570993664
0%401542651693022/download/1.pdf
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28. Optimizing Multi-Extraction (Cont’d)
How to Optimize Multi-Extraction?
Repeat extraction at least (3) times, to increase the overall analyte yield percentage.
Add fresh solvent after each extraction since previous solvent used had already reached
equilibrium or already saturated with the analyte.
Proper selection of the solvent based on the solubility of the analytes of interest.
Optimizing the temperature to allow a shorter extraction for the multiple extractions
time but not too high that is exceeds solvent boiling point.
Increasing the ultrasound power with each extraction would increase cavitation
resulting in more yield.[1]
[1] Zakaria, A. N. (2015). Extraction methods used in medicinal plants. Retrieved from
https://www.researchgate.net/profile/Arvind_Singh56/post/What_are_the_best_extraction_methods_for_herbal_plants/attachment/5bf2ff2dcfe4a764550348f1/AS%3A69474570993664
0%401542651693022/download/1.pdf
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30. Laboratory Scale Set-up
Materials/ Equipment:
Coffee
Diluted Sulphuric
Acid
Test tube
Measuring cylinder
Analytical balance
Oleander
Leaf, Ammonia
Filter paper
Separating funnel
Ethanol
Diethyl ether
Beaker
Funnel
Conical Flask
pH strip[1]
[1] Zakaria, A. N. (2015). Extraction methods used in medicinal plants. Retrieved from
https://www.researchgate.net/profile/Arvind_Singh56/post/What_are_the_best_extraction_methods_for_herbal_plants/attachment/5bf2ff2dcfe4a764550348f1/AS%3A69474570993664
0%401542651693022/download/1.pdf
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31. Laboratory Scale Set-up (Cont’d)
METHOD:
On an analytical balance, 2g of coffee powder was weighed and placed in a conical
flask, wetted with 5mL of ammonia in a hood fume, swirled and left for ten (10) minutes.
An aliquot amount of 25mL diethyl ether was poured in the flask and swirled continuously for five (5)
minutes.
The mixture was filtered and the filtrate collected in two (2 )separate test tubes then
placed in a centrifuge for 5 minutes.
After the allotted time, the supernatant was decanted and poured in a 100mL separating funnel.
The diethyl layer was extracted using two portions of 50mL diluted Sulphuric acid.[1]
[1] Zakaria, A. N. (2015). Extraction methods used in medicinal plants. Retrieved from
https://www.researchgate.net/profile/Arvind_Singh56/post/What_are_the_best_extraction_methods_for_herbal_plants/attachment/5bf2ff2dcfe4a764550348f1/AS%3A69474570993664
0%401542651693022/download/1.pdf
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