Fach: Galenik
Datum: 26.08.2021

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Ich hatte Suspension beim Leroux:

Leroux: Tell me what are suspensions?
Me: Liquid dosage form where solid particles are dispersed in a liquid.
Leroux: What are the advantages of suspension?
Me: Better than tablets because we don’t have to wait the time for disintegration since are already dispersed. Better than powders or granulates for the palatability. They are also good if the drug has a bitter taste since in suspension the drug is not dissolved.
Leroux: And also for old people and children why?
Me: It can be difficult to swallow tablets.
Leroux : Do you know an example of suspension?
Me: Antiacids.

Leroux: He showed me a paper with different equations. He asked me to explain the equation G=y*A related to suspension.
Me: By making suspension we increase the area and thus there is an increase of potential energy. For this reason, is necessary to add surfactant in order to decrease the surface tension.
Leroux: Can you name some surfactants?
Me: Ionic SDS, non-ionic Tween and Span.
Leroux: He showed me a paper with many different structures of surfactants. Can you indicate which is Tween, Span and SDS.
Leroux: By which mechanism the surfactant works?
Me: (not really sure since I studied surfactant only related to emulsion) but I said something like: “They can insert in the surface and disturb the packing”.
Leroux: This is the mechanical part but how they work…?
Me: ….” They remove intermolecular forces between the molecules”…
Leroux: Yes, so which is this type of interactions?
Me: …
Leroux: Electrostatic interactions.

Leroux: What other excipients can you add to suspension to increase stability?
Me: Antioxidants, preservatives and viscosity enhancers.
Leroux: Can you name some antioxidants and preservatives?
Me: Tocopherole but is for lipophile so I corrected and said is not used in suspension, then I said ascorbinsäure and Schwefelverbindungen. And preservatives Benzalkonium Chloride and Parabens. (What he wanted to hear was expecially ascorbic acid and paraben).

Leroux: He showed me the equation of velocity of sedimentation. Can you explain this equation?
Me: The equation shows that if we increase the size of the suspended particles there is more sedimentation and to avoid it we can increase the viscosity with viscosity increasing agents.
Leroux: Which viscosity increasing agents do you know?
Me: Sodium alginate and carboxmethylcellulose that are used to create plastic and pseudoplastic fluid.
Leroux: He showed me a paper with the four different graphs. Can you explain them?
Me: On the graphs we can see that if we use a normal Newtonian fluid, we have no changing in the viscosity whereas if we use a plastic or pseudoplastic we can see that by increasing the shearing stress there is an increasing in the rate of shear and the viscosity decreases. This mechanism is used to stabilize the solution during transport and storage by making them more viscous and then when they have to be administered, by shaking it is possible to decrease the viscosity.
Leroux: Can you indicate which is the graph of the plastic and which of the pseudoplastic and the what is it the fourth?
Me: No idea. (The answer was dilatant fluid).

Leroux: Which other methods to increase the viscosity do you know?
Me: ….mmh PEG.
Leroux: Yes and what it does?
Me: Is on the surface of particles and can limit the interactions between the particles of the dispersed phase to avoid interaction.
Leroux: And what happen if particle interact?
Me: There is aggregation that can give rise to flocculation and coagulation.
Leroux: Which is the difference between flocculation and coagulation?
Me: (not sure) …By coagulation it will form a compact cake whereas in flocculation is not so compacted.
Leroux: And how can you manage viscosity to avoid these phenomes?
Me: By adding salts.
Leroux: Exactly, and what you change by adding salts?
Me: The Zeta potential.


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My impression is that Leroux will ask more about every thing you say. For example, I said surfactant and he asked me which types. Then I explained the different types and he wanted to know the structure. So if you are not sure about something better not to say because you risk he want to know more about it 😉. In contrast you can try (with Leroux!) to bring the discussion to what you know better about the theme by mentioning some others details you know well.

11.08.2021 11.30
Medchem I&II

Q: Tell me about Hight throughput screening. How it is made and what it is used for.
A: It’s a method to find an appropriate lead for your target. You screen for millions of molecules. You have two different approaches: rationally and randomly. In the rationally you restrict your libraires whereas in the randomly you scan all the molecules.
Q: But how specific works the HTS?
A: I had no idea how it works specific, I only said: you have wells where you put first your target, then you put an agonist which can be fluorescent marked and then in every well you put a different molecule. When the right one binds to the target you have a signal (not really sure what he answered, he changed question…)
Q: You said there are millions of molecules where are the from?
A: …Database
Q: Yes, but they cost very much so where are they from?
A: …
Q: From natural product! What is the advantage and the disadvantage with natural product?
A: disadvantage: natural products are often very complicated structure so you have to simplify. Advantages: you can target also molecule that will not be drougable with normal molecules.
Q: True but normally you will not perform a HTS for molecules which are not drougable.
A: ...ok.


Q: Tell me what do you know about cholinergic receptor?
A: There are two different types, nicotinic is ion channel, muscarinic is GPCR.
Q: Acetylcholine will be hydrolyzed by acetylcholinesterase. Then he showed me the structure of acetylcholine in the acetylcholinesterase binding pocket. Where the esterase cleaves? And what is the function of serine?
A: it cleaves the ester group and serine make a nucleophilic attack.
Q: He showed me the structure of physostigmine and other acetylcholinesterase inhibitors.
Q: Can you draw the mechanism of inhibition?
A: I draw the mechanism (slide 41).
Q: What is the advantage for the structure of neostigmine and pyridostigmine?
A: Since the nitrogen is protonated, they will not pass the BBB and reduce side effect in the CNS:
Q: True, but also physostigmine has two nitrogen atoms.
A: I tried with maybe they are cleaved. (false 😉)
Q: The answer is that in physostigmine the nitrogen are only temporarily charged.


Q: Then he showed me a structure with the name (Palbociclib). I know you have never seen this structure. What can be?
A: It was a protein kinase since there was the typical aminopyrimidine group.
Q: What makes the aminopyrimidine group.?
A: It binds in the binding site where normally ATP can bind in kinases.
Q: It is possible that this molecule is a covalent inhibitor? and if yes which part of the molecule is the covalent inhibitor?
A: I had no idea…I tried with some group that seem to be reactive (like carbonyl, …)… sorry but I really didn’t understand his answer.
Q: About the group on the right (is a six member ring with N and NH), why the chemists add this group very often to the molecules?
A: Maybe the nitrogen atoms are reactive and can make some interactions in the active site.
Q: No, it’s not about pharmacodynamics.
A: mmm also for the pharmakokinetik.
Q: yes, because the nitrogen can be protonated an so it’s better soluble in water.
A: yes but so it pass the membrane difficult
Q: he answered it’s always a balance or something like that