Formulation of Anti-Microbials (severe infections)

What are the main choices of dosage form?

• oral/rectal administration

• IV/IM administration

What are advantages and disadvantages of oral administration?

• simplest, convenient and safest means of drug administration

• Potentially irregular absorption of certain drugs

What is main advantages capsules have over tablets?

• drug released faster using capsules than tablets

• Shell that masks taste of drug (some tablets have but not all)

What are disadvantages of tablets?

• poor bioavailability of some drugs

• Local irritant effects to the GI mucosa

What are advantages and disadvantage of powder formulations (oral)?

• faster dissolution rate than tablets or capsules

• not suitable for the administration of drugs which are inactivated in the stomach (same as with capsules)

• Less convenient to self administer

What are advantages and disadvantages of suspensions?

• convenient when drug is not soluble in water and when non-aqueous solvent cannot be used

Disadvantages = risk of sedimentation

What is phenoxymethylpenicillin used to treat?

• tonsillitis, otitis, rheumatic fever

What can be used to treat invasive aspergillosis?

• tablet = voriconazole, suspension = posaconazole

What can amoxicillin be used to treat?

• Lyme disease, h.pylori infection

What can tetracycline be used to treat?

• acne

What are advantages of rectal formulations?

• Good for drugs that get inactivated in GI when taken orally

• Good route when patient is vomiting

• Fast systemic response

What are disadvantages of rectal administration?

• less patient compliance

• Irregular drug absorption

What can be injected intravenously?

• only solutions

What are differences between injections and infusions

• injections are sterile solutions, emulsions or suspensions in water or non-aqueous liquid, injected in less than 15 mins

• Infusions are aqueous solutions that are administered in large volumes 100-1000ml and are injected in more than 15 mins

What are depot preparations?

Where are they injected and what quantity?

What are pros/cons of depot preparations?

• dispersion of the drug in an oily vehicle

• Injected IM and max 5ml at a time into a large muscle to decrease pain and swelling

• Slow release of the drug but can be quite painful

What are the components present in fungizone?

• Amphotericin (polyene) and sodium deoxycholate (surfactant)

What is the problem with fungizone?

• severe side effects

  • Renal toxicity

  • Haemotological toxicity

  • Cardiovascular toxicity

How does fungizone work to cause therapeutic effect?

Why does it result in toxicity?

• Amphotericin binds to ergosterol presents in fungal cell = therapeutic effect

• Toxicity because also targets cholesterol in mammalian cells

• So non-specific/ not selective

Where is ambisome drug located in the liposome?

• located within the liposome membrane (insert pic slide 30)

Why is ambisome better than fungizone?

• passive targeting of the liposomes to the infected organs

• Minimal exposure to non-target tissues (so don’t target mammalian cells)

What is structural differences between fungizone and ambisome in terms of targeting tissue and toxicity?

• for ambisome the Amphotericin stays encapsulated in liposome (lipid bilayer) so less toxic effects and better at targeting just fungal cells and not mammalian cells

• Fungizone, the Amphotericin leaks out of the micelle so it enters circulation, targets both fungal and mammalian cells = toxic effect

How much more toxic is fungizone than ambisome?

What is the main drawback of ambisome?

• 80 times more toxic

• Way more expensive than fungizone ( £24 vs £821) per vial