Lecture 10 - Industrial Production of Antibiotics Flashcards

1
Q

What are antibiotics?

A

compounds that kill bacteria or prevent the growth of bacteria

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2
Q

What is propolis?

A

a construction and repair material, sealant to fill gaps, smooth out internal wall

a natural product from the beehive

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3
Q

What is propolis used in?

A

creams, lotions, tinctures, toothpastes, sprays, mouthwashes

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4
Q

What properties did propolis have?

A

antibacterial, antifungal, antiviral effects

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5
Q

What was the first penicillin discovered?

A

benzylpenicillin

by Alexander Fleming (1928)

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6
Q

What can bacteria produce?

A

beta lactamases that will degrade beta lactam antibiotics

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7
Q

What is the 4 membered ring in beta lactams?

A

the active core of the molecule, but also its weakness

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8
Q

What does clavulanic acid too?

A

binds to the enzymes allowing the antibiotics to work effectively

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9
Q

Structure of clavulanic acid?

A

has the beta lactam ring, but no left side chain and does not posses any microbial activity on its own

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10
Q

How is clavulanic acid used?

A

with a penicillin to be active

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11
Q

What is augmentin?

A

amoxicillin (broad spectrum) + clavulanic acid

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12
Q

How is augmentin produced?

A

via fermentation, enzymation, extraction and isolation

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13
Q

How is benzylpenicillin produced?

A

by fermentation of penicillium

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14
Q

How is amoxicillin produced?

A

after additional enzymation and extraction

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15
Q

How is clavulanic acid produced?

A

by fermentation followed by solvent extraction and chemical salt conversion

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16
Q

How is augmentin then formed?

A

by isolation of each pure compound

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17
Q

What type of penicillin is amoxicillin classed as?

A

semi synthetic

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18
Q

What is clavulanic acid made from?

A

streptomyces clavuligerus

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19
Q

What is a monoculture?

A

we only want to keep the desired organism growing

20
Q

How much broth is made for clavulanic acid?

A

100,000L of broth every 12 hours

21
Q

What is a key challenge of fermentation of beta lactams?

A

the process is aqueous and the beta lactam structure is prone to hydrolysis

22
Q

What can improve the stability?

A

chilling batches and modifying the pH

23
Q

Why does stability need to be improved?

A

to mitigate losses

24
Q

What is benzylpenicillin made from?

A

penicillium chrysogenum (fungus)

25
Q

Steps of fermentation?

A

spore preparation

seed fermentation

production fermentation

harvest

26
Q

What is benzylpenicillin converted to?

A

6-APA (aminopenicillanic acid) by enzymatic cleavage of the amide side chain

27
Q

How can amoxicillin be made?

A

either synthetic or enzymatic processes can be used to add alternative side chains to th 6-APA core molecule

28
Q

After fermentation, what is the ‘broth’?

A

a dilute mixture containing large molecules, trace salts, proteins, dissolved materials

29
Q

What is membrane technology used to do?

A

filter through fine membranes and then reverse osmosis to concentrate the volume down to a manageable amount

30
Q

What does resin treatment do?

A

absorbs proteins that would precipitate in solvent mixtures downstream

31
Q

What is post initial clean up?

A

material is fed into a continuous solvent extraction loop

32
Q

What do delays in extraction cause?

A

degradation and efficiency losses

pH and temperature are important in managing stability challenges

33
Q

Steps of extraction?

A

ultrafiltration

reverse osmosis

resin

forwrd extraction

carbon treatment

34
Q

What does carbon treatment do?

A

treatment to remove coloured impurities

adsorbs coloured impurities associated with any degradation prior to isolation

35
Q

What is critical when extracting from aqueous into solvent?

A

the ratios, pH and temperature

ensures effective extraction with minimal degradation losses of the unstable material at low pH

36
Q

What are the steps of isolation?

A

back extraction

intermediate isolation

K salt conversion

pre-mix blend

37
Q

What does isolation do?

A

isolates the product that we are interested in

38
Q

What is back extraction?

A

the material is back extracted into an aqueous solution, the pH adjusted to control byproduct impurities that carry through the extraction processes and then crystallised to solvent

39
Q

What do washing and drying do?

A

ensure product quality not just at the point of manufacture but throughout the product shelf life

40
Q

What does increased moisture during storage lead to?

A

degradation

41
Q

What is potassium clavulanate isolated as?

A

not pure active pharmaceutical ingredient but is blended with inert excipients prior to being formulated into a drug

42
Q

What do pharmaceutical industries need to ensure?

A

that the processes involved in developing, producing, testing and distributing their drug products do not negatively affect the quality and efficacy nor patient safety

43
Q

What is vital?

A

that product quality is built into all stages of industrial production and this involves applying a product lifecycle management approach

44
Q

What are the 3 stages of the PLM?

A

stage 1 - process design

stage 2 - process qualification

stage 3 = continued process verification

45
Q

What is root cause analysis?

A

identifying the problem and fixing exactly what it is

46
Q

What is technical risk assessment?

A

to predict technical and operational risks based on knowledge and process understanding, implementing mitigation actions to prevent issues from occuring

47
Q

What is vital to ensure product quality?

A

understanding the link between critical parameters and critical atrributes