100% tevredenheidsgarantie Direct beschikbaar na je betaling Lees online óf als PDF Geen vaste maandelijkse kosten
logo-home
Eerder door jou gezocht
Eerder door jou gezocht
logo
Pharmaceutical Manufacturing Techniques Summary €13,46
In winkelwagen
Snel navigeren naar
Voorbeeld
  2.  
  3. Universiteit Gent (UGent)
  4.  
  5. Pharmaceutical Manufacturing Techniques
  6.  
  7. J000449A (J000449A)

Samenvatting

Pharmaceutical Manufacturing Techniques Summary

 0 keer verkocht
  • Vak
  • J000449A (J000449A)
  • Instelling
  • Universiteit Gent (UGent)

Deze samenvatting werd gemaakt o.b.v. de slides en lesinhoud van het vak pharmaceutical manufacturing techniques, gedoceerd in de tweede master geneesmiddelenontwikkeling. Het werd in het Engels opgesteld aangezien de cursus en lessen ook in het Engels waren.

Voorbeeld 4 van de 91  pagina's

Document informatie

  • 10 januari 2025
  • 91
  • 2024/2025
  • Samenvatting

Onderwerpen

  • pharmaceutical sciences
  • 2nd master
  • drug development
  • summary
  • samenvatting
  • pharmaceutical manufacturing techniques
  • pharmaceutical manufacturing
  • farmaceutische wetenschappen
  • geneesmiddelenontwikkeling

Geschreven voor

  • Universiteit Gent (UGent)
  • Pharmaceutical Manufacturing Techniques
  • J000449A (J000449A)
Alle documenten voor dit vak (1)

Verkoper

avatar-seller
lkfjqosidfj

Ontvangen beoordelingen

Voorbeeld van de inhoud

SV pharmaceutical manufacturing techniques 2024 – 2025


Inhoudsopgave
1 Solid Phase Peptide Synthesis ............................................................................................... 3
1.1 Combinatorial chemistry ....................................................................................................... 3
1.1.1 Combinatorial libraries ................................................................................................... 3
1.2 High throughput synthesis ..................................................................................................... 9
1.2.1 Solid phase synthesis ..................................................................................................... 9
1.2.2 Solid phase synthesis vs. synthesis in solution .............................................................. 26

2 Nanotechnological Formulation of Poorly Water-Soluble Drug Molecules............................... 27
2.1 Nanotechnology in Pharmaceutical Industry .........................................................................27
2.1.1 Introduction ................................................................................................................. 27
2.1.2 Poorly Soluble API’s require new techniques… .............................................................. 28
2.1.3 Block Copolymer Micelles ............................................................................................ 30
2.1.4 Nano Emulsions ........................................................................................................... 30
2.2 Nanosuspensions ................................................................................................................32
2.2.1 Introduction ................................................................................................................. 32
2.2.2 Examples of Nanosuspensions ..................................................................................... 33
2.2.3 Producing nanosuspensions ......................................................................................... 34
2.3 Downstream Processing of Nanosuspensions .......................................................................37
2.3.1 Nanosuspensions into solid dosage forms .................................................................... 37
2.4 Case study ..........................................................................................................................42
2.4.1 Doxil ............................................................................................................................ 42
2.4.2 Cripec.......................................................................................................................... 43

3 Continuous Production, QbD, PAT ......................................................................................... 46
3.1 Introduction .........................................................................................................................46
3.1.1 Continuous manufacturing ........................................................................................... 46
3.1.2 PAT .............................................................................................................................. 47
3.1.3 QbD ............................................................................................................................. 48
3.2 Pharmaceutical applications ................................................................................................49
3.3 Hot melt extrusion ...............................................................................................................50
3.3.1 Introduction ................................................................................................................. 50
3.3.2 Solid dispersions .......................................................................................................... 51
3.3.3 CMA’s and CPP’s for hot melt extrusion......................................................................... 52
3.3.4 Downstream processing ............................................................................................... 54
3.3.5 PAT in hot melt extrusion .............................................................................................. 54
3.4 Continuous wet granulation: twin screw granulation ..............................................................54
3.4.1 Introduction ................................................................................................................. 54
3.4.2 Screw based granulation .............................................................................................. 55
3.4.3 PAT during wet granulation............................................................................................ 55
3.4.4 Granule Size Distribution (GSD) as a CQA ...................................................................... 55
3.4.5 Friability as a CQA ........................................................................................................ 57
3.4.6 PAT in wet granulation .................................................................................................. 57

4 Process Chemistry and API Manufacturing ............................................................................ 58
4.1 Need for process chemistry ..................................................................................................58
4.2 Process chemistry ...............................................................................................................58
4.2.1 Process chemistry ¹ medicinal chemistry ...................................................................... 58
4.2.2 API production cost ...................................................................................................... 59

,SV pharmaceutical manufacturing techniques 2024 – 2025


4.2.3 ICH guidelines on process equipment ........................................................................... 59
4.3 Reaction engineering and catalysis .......................................................................................60
4.3.1 Reaction engineering .................................................................................................... 60
4.4 Chemical reactor engineering ...............................................................................................62
4.4.1 Reactor engineering ..................................................................................................... 62
4.5 API separation and purification .............................................................................................64
4.5.1 API separation .............................................................................................................. 64
4.5.2 API purification............................................................................................................. 65
4.6 Click chemistry and biorthogonal chemistry ..........................................................................68
4.6.1 Click chemistry ............................................................................................................ 68
4.6.2 Biorthogonal chemistry................................................................................................. 69

5 3D Printing & Electrospinning ................................................................................................ 70
5.1 3D-printing ..........................................................................................................................70
5.1.1 What is 3D printing? ..................................................................................................... 70
5.1.2 3D printing technologies ............................................................................................... 71
5.1.3 Other biomedical applications of 3D printing ................................................................. 74
5.2 Electrospinning ....................................................................................................................74
5.2.1 What is electrospinning? .............................................................................................. 74
5.2.2 Parameters & variables ................................................................................................. 75
5.2.3 Porous fibers ................................................................................................................ 77
5.2.4 Drug delivery ................................................................................................................ 77
5.2.5 Tissue engineering ........................................................................................................ 78
5.3 Electrospraying ....................................................................................................................78
5.3.1 What is electrospraying? .............................................................................................. 78
5.4 Case study ..........................................................................................................................79
5.4.1 Flubendazole ............................................................................................................... 79

6 mRNA Lipid Nanoparticle Formulation .................................................................................. 80
6.1 mRNA LNP formulation characterization and activity testing ..................................................80
6.1.1 Dynamic light scattering (DLS) & field flow fractionation: techniques to measure particle
size 80
6.1.2 Electrophoretic mobility ............................................................................................... 83
6.1.3 Flow cytometry............................................................................................................. 84
6.1.4 Reporter proteins ......................................................................................................... 86
6.2 Microfluidic production ........................................................................................................87
6.2.1 What is microfluidics? .................................................................................................. 87
6.2.2 Microfluidic chips and devices ...................................................................................... 87
6.2.3 Microfluidic flow........................................................................................................... 87
6.2.4 Microfluidic emulsification ........................................................................................... 87
6.2.5 Microfluidic nanoprecipitation ...................................................................................... 89
6.3 mRNA LNP vaccines ............................................................................................................90
6.3.1 virus vector DNA and mRNA vaccines............................................................................ 90
6.3.2 mRNA LNP formulation ................................................................................................. 90

,SV pharmaceutical manufacturing techniques 2024 – 2025




1 Solid Phase Peptide Synthesis
Classical organic synthesis in solution
- Most cases: reagent A + reagent B à product AB
ð Classic method for conventional (simple) compounds
ð Possible through applying specific reactions and conditions: temperature, time, ratio,
solvent, catalyst, base…
- Complexity: chemists could make up to 100 compounds a year, however this was too little
when high throughput screening became a hot topic
ð Therefore, we needed high throughput synthesis!



Principle: synthesis of multiple different compounds at the same time.
ð Simultaneous preparation of a library (a.k.a. different compounds) at once, under
identical conditions.
« classical synthesis provides us with one compound at a time

Classical chemistry Combinatorial chemistry
Starting materials: Starting materials:
Reagent A i reagents A
Reagent B n reagents B

Reaction: A + B ® AB Reactions: A1 + B1 ® A1B1…
…Ai + Bn ® AiBn
Output: 1 product Output: i*n products

1.1.1 Combinatorial libraries
1.1.1.1 types of combinatorial libraries
Scaffold-based: libraries where the scaffold or core structure is always the same, only the “R”-
groups differ.
e.g. Passerini three-component reaction

Scaffold: the core structure or framework of a molecule, around which other chemical groups are
added.
ð This central framework is often responsible for the biological activity
ð Scaffold is like the “skeleton” on which functional groups or side chains “clothing” are
added.

Backbone-based: libraries where the compounds are related by a common backbone, which
always repeats itself.
e.g. Oligopeptides made from 20 different amino acids.

Backbone: the entire structure of a molecule, including both the scaffold and the attached
functional groups.
ð Considers the full molecule as a whole

, SV pharmaceutical manufacturing techniques 2024 – 2025


ð Allows the exploration of different complete molecular structures.
ð Backbone is more like “the entire outfit”
ð Different molecules with varying overall structures are included in the library, not just
variations around a common core.

Key Difference
- Focus: Scaffold-based libraries focus on a shared central framework with varying side
groups, while backbone-based libraries focus on complete, diverse molecular structures.
- Purpose: Scaffold-based libraries are used to systematically explore variations around a
common core, while backbone-based libraries are broader, aiming to maximize chemical
diversity.

1.1.1.2 size of combinatorial libraries
Few 10’s – 100’s – 1000’s of compounds

𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑠𝑦𝑛𝑡ℎ𝑒𝑠𝑖𝑧𝑒𝑑 𝑐𝑜𝑚𝑝𝑜𝑢𝑛𝑑𝑠
= (# 𝑏𝑢𝑖𝑙𝑑𝑖𝑛𝑔 𝑏𝑙𝑜𝑐𝑘𝑠 𝑢𝑠𝑒𝑑 𝑝𝑒𝑟 𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛 𝑠𝑡𝑒𝑝)!"#$%& () &%*+,-(! .,%/.01


1.1.1.3 requirements
! Large collection of reactive, small and structurally different building blocks
! Synthesis:
o Fast
o Reproduceable
o Reliable

1.1.1.4 synthesis methods
Parallel synthesis: where multiple compounds are synthesized simultaneously in separate
reactions.

Split synthesis: where a single pool of reactants is split, reacted, and recombined iteratively1 to
generate a diverse library of compounds.

1.1.1.4.1 PARALLEL SYNTHESIS
“The easiest library synthesis.”
ð Each reaction vessel contains an individual reaction/individual compound.
ð Binding and activity screening is possible in solution and on-bead.
ð Automation is possible

Total individual reactions = number of end products * reaction steps
Number of end products = (number of reactions)^(number of building blocks in every step)

Step 1: well with solid support in each reaction vessel.
¢: solid support
¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢
¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢
¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢

Step 2: couple A, B and C to the solid support
¢-A ¢-A ¢-A ¢-A ¢-A ¢-A ¢-A ¢-A ¢-A

1
Repeating cycles of splitting, reacting, and recombining multiple times to systematically build a diverse
library of compounds.

Dit zijn jouw voordelen als je samenvattingen koopt bij Stuvia:

Bewezen kwaliteit door reviews

Bewezen kwaliteit door reviews

Studenten hebben al meer dan 850.000 samenvattingen beoordeeld. Zo weet jij zeker dat je de beste keuze maakt!

In een paar klikken geregeld

In een paar klikken geregeld

Geen gedoe — betaal gewoon eenmalig met iDeal, creditcard of je Stuvia-tegoed en je bent klaar. Geen abonnement nodig.

Direct to-the-point

Direct to-the-point

Studenten maken samenvattingen voor studenten. Dat betekent: actuele inhoud waar jij écht wat aan hebt. Geen overbodige details!

Veelgestelde vragen

Wat krijg ik als ik dit document koop?

Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.

Tevredenheidsgarantie: hoe werkt dat?

Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.

Van wie koop ik deze samenvatting?

Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper lkfjqosidfj. Stuvia faciliteert de betaling aan de verkoper.

Zit ik meteen vast aan een abonnement?

Nee, je koopt alleen deze samenvatting voor €13,46. Je zit daarna nergens aan vast.

Is Stuvia te vertrouwen?

4,6 sterren op Google & Trustpilot (+1000 reviews)

Afgelopen 30 dagen zijn er 64257 samenvattingen verkocht

Opgericht in 2010, al 15 jaar dé plek om samenvattingen te kopen

Begin nu gratis

Laatst bekeken door jou

Samenvatting ·

(0)

Samenvatting methoden in het biomedisch onderzoek 3 2024

Voordeelbundel ·

(0)

AQA A-level CHEMISTRY 7405/2 Paper 2 Organic and Physical Chemistry with Mark scheme June 2023

Samenvatting ·

(0)

Samenvatting - Basis van de hulpverlening (belangrijk)

Samenvatting ·

(0)

Leerpad E - respectvol verplegen

€13,46
  • (0)
In winkelwagen
Toegevoegd