Lecture 10 - Industrial Production of Antibiotics Flashcards by Phoebe Roper

What are antibiotics?

compounds that kill bacteria or prevent the growth of bacteria

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What is propolis?

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

a natural product from the beehive

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What is propolis used in?

creams, lotions, tinctures, toothpastes, sprays, mouthwashes

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What properties did propolis have?

antibacterial, antifungal, antiviral effects

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What was the first penicillin discovered?

benzylpenicillin

by Alexander Fleming (1928)

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What can bacteria produce?

beta lactamases that will degrade beta lactam antibiotics

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What is the 4 membered ring in beta lactams?

the active core of the molecule, but also its weakness

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What does clavulanic acid too?

binds to the enzymes allowing the antibiotics to work effectively

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Structure of clavulanic acid?

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

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How is clavulanic acid used?

with a penicillin to be active

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What is augmentin?

amoxicillin (broad spectrum) + clavulanic acid

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How is augmentin produced?

via fermentation, enzymation, extraction and isolation

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How is benzylpenicillin produced?

by fermentation of penicillium

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How is amoxicillin produced?

after additional enzymation and extraction

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How is clavulanic acid produced?

by fermentation followed by solvent extraction and chemical salt conversion

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How is augmentin then formed?

by isolation of each pure compound

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What type of penicillin is amoxicillin classed as?

semi synthetic

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What is clavulanic acid made from?

streptomyces clavuligerus

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What is a monoculture?

we only want to keep the desired organism growing

How much broth is made for clavulanic acid?

100,000L of broth every 12 hours

What is a key challenge of fermentation of beta lactams?

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

What can improve the stability?

chilling batches and modifying the pH

Why does stability need to be improved?

to mitigate losses

What is benzylpenicillin made from?

penicillium chrysogenum (fungus)

Steps of fermentation?

spore preparation seed fermentation production fermentation harvest

What is benzylpenicillin converted to?

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

How can amoxicillin be made?

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

After fermentation, what is the 'broth'?

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

What is membrane technology used to do?

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

What does resin treatment do?

absorbs proteins that would precipitate in solvent mixtures downstream

What is post initial clean up?

material is fed into a continuous solvent extraction loop

What do delays in extraction cause?

degradation and efficiency losses pH and temperature are important in managing stability challenges

Steps of extraction?

ultrafiltration reverse osmosis resin forwrd extraction carbon treatment

What does carbon treatment do?

treatment to remove coloured impurities adsorbs coloured impurities associated with any degradation prior to isolation

What is critical when extracting from aqueous into solvent?

the ratios, pH and temperature ensures effective extraction with minimal degradation losses of the unstable material at low pH

What are the steps of isolation?

back extraction intermediate isolation K salt conversion pre-mix blend

What does isolation do?

isolates the product that we are interested in

What is back extraction?

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

What do washing and drying do?

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

What does increased moisture during storage lead to?

degradation

What is potassium clavulanate isolated as?

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

What do pharmaceutical industries need to ensure?

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

What is vital?

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

What are the 3 stages of the PLM?

stage 1 - process design stage 2 - process qualification stage 3 = continued process verification

What is root cause analysis?

identifying the problem and fixing exactly what it is

What is technical risk assessment?

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

What is vital to ensure product quality?

understanding the link between critical parameters and critical atrributes