Pharmaceutics

Question 1

What should be considered when formulation eye drops

Answer 1

PH close to 7.4 (better alkali than acidic)
Isotonic (better hypo than hyper)

Question 2

Why does eye drug have low absorption into anterior segment

Answer 2

• drug diluted by tear film causing low concentration in contact with cornea
• short contact time with cornea only 2-3 mins
  -Absorbed into systemic circulation via nasal mucosa or GI tract
• protein binding in the tear film causing large particle size
• corneal barrier

Question 3

Most ear drops are made of oil, glycerol and propylene glycol. T or F?

Answer 3

True

Water promotes bacterial growth
Earwax is hydrophobic
Oil can soften wax and allow better drug penetration. Whereas glycerol, PG are hygroscopic which reduces oedema

Question 4

How can drug be delivered to the middle ear

Answer 4

Via systemic delivery or injection through eardrum

Question 5

What are the characteristics of the cornea making it hard for drug absorption?

Answer 5

Small surface area
Multilayered epithelium with tight junctions
Drugs must be able to cross cell layer (lipophyllic) and stroke that’s hydrophillic

Question 6

What drug is given to treat epistaxis (nose bleed)

Answer 6

BIPP bismuth iodoform paraffin paste

Question 7

Where in the nasal region does drug absorption happen and why

Answer 7

Respiratory region containing turbinates( curled spongy bones)

Pseudostratified columnar epithelium.
Large SA of 130cm2
Very high vascularization
High permeability
Prolonged contact time (turbinates)

Question 8

What does the mucus consist of

Answer 8

Water, salt, enzyme, mucin, immunoglobulin, lysozyme

Question 9

Advantages of systemic nasal delivery

Answer 9

Easy access

Non invasive

Avoid first pass met (but enzymes present in nose as well)

Rapid absorption and onset of action (antimigraine and opioids)

Question 10

What should be taken into consideration when formulating nasal sprays

Answer 10

Particle size > 50micrometer
Deposition by inertial impaction so it doesn’t enter lungs
Must not interfere with ciliary clearance (viscosifying agengs and preservative might affect)

Question 11

Peptides such as insulin cannot be administered through nasal delivery but not oral delivery

T or F

Answer 11

False
Peptides can be administered through the nasal cavity and not orally as the GI system digests peptides
Only short peptides can be delivered
Can use as vaccine delivery instead of injection

However, bioavailability is low

Question 12

Explain steam sterilisation

Answer 12

Saturated steam under pressure in autoclave
121oC for 15 min or 134oC for 3 mins
Denature essential cell constituents of organism
Items are packed to allow steam penetration and post sterilisation protection

Question 13

ExplainDry heat sterilisation

Answer 13

Sterilised in hot air oven
160o 2 hours or 170 for 1 hr
Kills microorganism via oxidative processes
Sterilis eglass bottle and metal surgical instruments
Can kill pyrogens that cause fever

Question 14

Why can’t ointment be sterilised with heat? What method is used

Answer 14

Ointment will change in composition due to heat

Use ionising radiation

Question 15

What sterilisation process acts by chemically modifying proteins and nucleic acid for biocide activity

Answer 15

Gaseous method with ethylene oxide or formaldehyde

Question 16

What are the disadvantage of using gaseous sterilisation method

Answer 16

Formaldehyde and ethylene oxide are mutagenic and carcinogenic
Staff must be protected

Question 17

What is the pore diameter of membrane filter for aseptic sterilisation
A. 0.3nm
B. 1.00nm
C. 0.22 um

Answer 17

C. 0.22uM

Question 18

What are 3 routes drug can use to cross the stratum corneum (skin)

Answer 18

Intercellular
Transcellular
Transappendageal (shunt route)

Question 19

What are the advantages and disadvantages of topical drug delivery

Answer 19

Adv:
Painless and easy delivery
Patients compliance
Avoids first pass met
Increased efficacy
Decreased side effects

Dis:
Allergies/ irritations
Only few drugs can use topical delivery
Drug metabolism by enzymes
Low drug penetration into skin

Question 20

Hydrated skin prevents drug penetration. T or F

Answer 20

False
Increased hydration is better for hydrophilic and lipophyllic drugs

Other factors include age, body site and pathological disorders

Question 21

For a topical drug, what molecular weight, partition coefficient (logP), and pH should be used for optimal permeation?

Answer 21

Molecular weight less than 500Da
LogP less than 3 (or else accumulate in stratum corenum)
PH Of skin (5)

Question 22

What are occlusion in topical drug delivery

Answer 22

Ointment or water in oil cream that prevents water evaporation from skin.
Increases hydration and drug permeation

Question 23

How does permeation enhancers work? Give examples

Answer 23

• modify keratin conformation: encourage swelling and increase hydration (DMSO, urea)
• disrupt lipid bilayer: increase permeability (fatty acids, surfactant)
• alter solvent properties of stratum corneum (DMSO, ethanol, propylene glycol)

Question 24

What are the factors affecting drug permeation across the skin

Answer 24

Moisture: more moist = better absorption for hydrophilic and lipphilic drugs

Age: skin thickness peak at 40 then decreases from 50s, older means less moist

Body site: different thickness- genitals>face and neck >trunk>arms>legs

Pathological disorders

Question 25

What is the optimal molecular weight and partition coefficient for a topical drug

Answer 25

<500 Da for good penetration
LogP 1-3

Question 26

How are topical pro drugs modified?

Answer 26

Add lipophilic moiety to increase partitioning into stratum corneum

Add esters which are cleaved by eateries to release parent molecule

Question 27

Examples of permeation enhancer components

Answer 27

Fatty acid and surfactants
Urea
Turpene
Solvents - dimethylsulfoxide, ethanol, propylene glycol

Question 28

Limitations of nasal drug delivery

Answer 28

Mucus can prevent absorption
Only 100-150ul drug can be delivered
Mucociloary clearance every 15-20 minutes
Must be low molecular weight (<1kDA)
High levels of protease and cCYP450
Nasal irritation
Taste/ smell problem

Question 29

Nasal drug formulation design

Answer 29

Liquid formulation must match nasal secretion (pH, isotonic)
Cosolvent - glycerol, propanol, propylene glycol
Flavourings, preservatives, antioxidants, viscosifying agents (increase contact time)

Must not interfere with ciliary clearance (often happens with antioxidant and viscosifying agent)