Pharmaceutics Flashcards
What should be considered when formulation eye drops
PH close to 7.4 (better alkali than acidic)
Isotonic (better hypo than hyper)
Why does eye drug have low absorption into anterior segment
- 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
Most ear drops are made of oil, glycerol and propylene glycol. T or F?
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
How can drug be delivered to the middle ear
Via systemic delivery or injection through eardrum
What are the characteristics of the cornea making it hard for drug absorption?
Small surface area
Multilayered epithelium with tight junctions
Drugs must be able to cross cell layer (lipophyllic) and stroke that’s hydrophillic
What drug is given to treat epistaxis (nose bleed)
BIPP bismuth iodoform paraffin paste
Where in the nasal region does drug absorption happen and why
Respiratory region containing turbinates( curled spongy bones)
Pseudostratified columnar epithelium.
Large SA of 130cm2
Very high vascularization
High permeability
Prolonged contact time (turbinates)
What does the mucus consist of
Water, salt, enzyme, mucin, immunoglobulin, lysozyme
Advantages of systemic nasal delivery
Easy access
Non invasive
Avoid first pass met (but enzymes present in nose as well)
Rapid absorption and onset of action (antimigraine and opioids)
What should be taken into consideration when formulating nasal sprays
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)
Peptides such as insulin cannot be administered through nasal delivery but not oral delivery
T or F
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
Explain steam sterilisation
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
ExplainDry heat sterilisation
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
Why can’t ointment be sterilised with heat? What method is used
Ointment will change in composition due to heat
Use ionising radiation
What sterilisation process acts by chemically modifying proteins and nucleic acid for biocide activity
Gaseous method with ethylene oxide or formaldehyde
What are the disadvantage of using gaseous sterilisation method
Formaldehyde and ethylene oxide are mutagenic and carcinogenic
Staff must be protected
What is the pore diameter of membrane filter for aseptic sterilisation
A. 0.3nm
B. 1.00nm
C. 0.22 um
C. 0.22uM
What are 3 routes drug can use to cross the stratum corneum (skin)
Intercellular
Transcellular
Transappendageal (shunt route)
What are the advantages and disadvantages of topical drug delivery
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
Hydrated skin prevents drug penetration. T or F
False
Increased hydration is better for hydrophilic and lipophyllic drugs
Other factors include age, body site and pathological disorders
For a topical drug, what molecular weight, partition coefficient (logP), and pH should be used for optimal permeation?
Molecular weight less than 500Da
LogP less than 3 (or else accumulate in stratum corenum)
PH Of skin (5)
What are occlusion in topical drug delivery
Ointment or water in oil cream that prevents water evaporation from skin.
Increases hydration and drug permeation
How does permeation enhancers work? Give examples
- 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)
What are the factors affecting drug permeation across the skin
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
What is the optimal molecular weight and partition coefficient for a topical drug
<500 Da for good penetration
LogP 1-3
How are topical pro drugs modified?
Add lipophilic moiety to increase partitioning into stratum corneum
Add esters which are cleaved by eateries to release parent molecule
Examples of permeation enhancer components
Fatty acid and surfactants
Urea
Turpene
Solvents - dimethylsulfoxide, ethanol, propylene glycol
Limitations of nasal drug delivery
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
Nasal drug formulation design
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)
