formulations of anti-microbials

Question 1

characteristics of a topical drug

Answer 1

• low MW (less than 500)
• moderately lipophilic (logP 1-4)
• effective at low dose (daily dose of less than 10mg)

Question 2

liquid formulations

Answer 2

• single-phase solutions/lotions
• rapid short term input of permeant into skin
• poor residence time on the skin
• evaporation of solvent (alcoholic vehicle)
  EXAMPLES: erythromycin solution, clindamycin lotion

Question 3

semi-solid formulations

Answer 3

• ointments, gels, creams
• good residence time on the skin
• good acceptance from patients
  semi-solid base:
• hydrophobic (liquid paraffin, glycerides, waxes)
• hydrophilic (polyethylene glycol PEG)

Question 4

ointments

Answer 4

• hydrophobic, fatty preparations
• highly occlusive (non-permeable)
• used on dry lesions
• prolonged drug delivery
• messy to use
  EXAMPLES: mupirocin, fusidic acid (staphylococcus infection: impetigo)

Question 5

gels

Answer 5

• formed from a liquid phase that is thickened with other components (i.e. PEG, polymers: carbomer)
• liquid phase maybe alcoholic, solvent may evaporate
  EXAMPLE: metronidazole gel (rosacea)

Question 6

creams

Answer 6

• made of 2 phased emulsion: water-in-oil or oil-in-water
• water-in-oil emulsions less greasy than ointments
• easier to apply
• can be washed off
• less occlusive than ointments
• less beneficial in dry skin conditions
  EXAMPLES: mupirocin, neomycin, fusidic acid

Question 7

solid formulations

Answer 7

• spray powders
• incorporate a volatile solvent (ethanol) that dissolves some drug prior to evaporation
  EXAMPLE: miconazole nitrate (fungal skin infection: athletes foot)

Question 8

nail solid formulations

Answer 8

• nail lacquer
• keratolytic components (urea) to increase diffusion of the drug through the nail plate
  EXAMPLE: amorolfine

Question 9

eye solutions

Answer 9

• easy to administer
• homogeneous (better dose uniformity)
• rapidly drained out of eye
• lack of efficacy
  EXAMPLES: chloramphenicol, ciprofloxacin (corneal ulcers)

Question 10

eye ointments

Answer 10

• mainly used of lipophilic excipients (petrolatum, lanolin)
• reduce drug drainage caused by tear flow
• increase of corneal residence time
• sustained drug release (2-4 hrs)
• more difficult to administer than solutions
• blurring of vision
  EXAMPLES: chloramphenicol, ciprofloxacin

Question 11

ear solutions

Answer 11

• viscous formulations
• increase residence time of the formulation
• prolonged contact with the area of infection
  EXAMPLES: chloramphenicol, clotrimazole (otitis)

Question 12

nose formulations

Answer 12

• creams, ointments
• mucocilliary clearance (removal of the drug from the nasal cavity)
• bioadhesion needed for increased nasal residence time
  EXAMPLES: mupirocin, chlorhexidine + neomycin (staphylococci)

Question 13

oropharyngeal formulations

Answer 13

• solutions, gels, suspensions, mucoadhesive buccal tablets
• suspensions deposit antimicrobial drug on mucosa surface
• improvement of residence time of drug but dissolution needed prior permeation
  EXAMPLES:
• miconazole gel and mucoadhesive tablets (fungal infections: thrush, candidiasis)
• Nystatin suspension (fungal)
• chlorhexidine mouth wash

Question 14

vagina formulations

Answer 14

• gels, creams, pessaries, ovules
• pessary: solid, single-dose formulation of ovoid shape
• ovules (vaginal capsules): solid single-dose formulations
• treatment of local infections with low dose than with oral administration
• no need of absorption of drugs for local action
• release of the drugs influenced by varying volumes of vaginal fluid
  EXAMPLES:
• clotrimazole (cream/pessary)
• antifungal miconazole (ovule)
• metronidazole (gel)

Question 15

oral administration

Answer 15

• drug absorption through epithelia and mucosa of GI tract
• most convenient and safest form
• possibility of irregular absorption of certain drugs

Question 16

tablets

Answer 16

• accurate dosing of the drug
• convenient to handle
• easy to take
• controlled release of the drug
• poor bioavailability of some drugs
• local irritants effects the GI tract

Question 17

capsules

Answer 17

• accurate dosing of drug
• drug released faster than tablets
• use of colour for identification
• easy to swallow
• shell masks taste
• good patient compliance
• bulky material can result in large capsule size
• susceptible yo moisture

Question 18

powders

Answer 18

• reconstituted just before use to avoid chemical degradation
• faster dissolution rate than tablets/capsules
• less convenient to carry and administer

Question 19

suspensions

Answer 19

• drug absorption faster than tablets/capsules
• insoluble solids act as reservoir
• slow/prolonged release of drug
• risk of sedimentation

Question 20

syrup

Answer 20

• drug already dissolved
• absorption faster than solid dosage forms
• masks unpleasant taste
• easy to adjust dose for child’s weight
• risk of deterioration
• inaccuracy in doses as patient is measuring with spoon

Question 21

rectal administration

Answer 21

• suppositories
• for drugs that are inactivated by GI fluids/liver when given orally
• good route to administer when vomiting
• faster systemic response
• patient unacceptability
• drug absorption: irregular/difficult to predict

Question 22

parenteral administration

Answer 22

• intramuscular and intravenous administrations
• must be sterile
• preferred route when rapid absorption is essential
• sterile solutions/suspensions of drugs in water

Question 23

injections

Answer 23

• sterile solutions, emulsions, suspensions in water, non-aqueous liquids
• injected in less than 15 mins

Question 24

infusions

Answer 24

• aqueous solutions
• large volumes: 100-1000 ml
• injected in more than 15 mins

Question 25

depot preparation

Answer 25

- dispersion of drug in oily vehicle - intramuscular injection deep into skeletal muscle - viscous formulation - large volume - slow release of antibiotic for weeks

Question 26

benzathine penicillin G

Answer 26

- patients who have had acute rheumatic fever and need prophylaxis against further streptococcal infections

Question 27

liposomes

Answer 27

- spherical vesicles which a lipid bilayer membrane delimitates a central aqueous compartment - carry hydrophobic and lipophilic drugs - they form when phospholipids are exposed to an aqueous environment

Question 28

fungizone [amphotericin]

Answer 28

- antifungal agent used to treat invasive fungal infections (candidiasis) - sterile lyophilised powder - micellar dispersion of amphotericin and sodium deoxycholate - administered as an IV infusion over 20-30 mins

Question 29

micelle

Answer 29

assembly of surfactant molecules in water with hydrophilic head regions in contact with surrounding solvent sequestering the hydrophobic tail regions in micelle centre

Question 30

adverse effects of amphotericin

Answer 30

- renal toxicity: >80% of patients - haematological toxicity: severe thrombocytopenia, leukopenia, haemoglobin reduction) - cardiovascular toxicity (cardiac arrest)

Question 31

amphotericin mode of action

Answer 31

- binds to ergosterol present in fungal cell membranes giving a therapeutic effect - also binds to cholesterol present in mammalian healthy cells membranes making it toxic

Question 32

AmBisome

Answer 32

- small unilamellar vesicle - single bilayer, less than 100nm - drug intercalated within the liposome membrane - 80% less toxic than fungizone - prolonged circulation in vivo - direct interaction with fungal cells - minimal interaction with mammalian cells - minimal exposure of non-target tissues disadvantages: - interaction with blood opsonin - liposomes end up in the tissue of mononuclear phagocytosis system (MPS) mostly fixed to macrophages in the liver + spleen