Exam 4 Spring 2017 Flashcards
How do you apply semi-solid preparations?
topically
What are examples of non-medicated semi-solid preparations?
- emollient (moisturizer)
- skin protectant
What are the classifications of bases for semi-solids?
- oleaginous
- absorption
- water removable
- greaseless
other names for oleaginous bases
- hydrocarbon bases
- hydrophobic bases
oleaginous base properties
- highest occlusion properties
- most oily
- difficult to wash off skin
- difficult to incorporate aqueous agents
- immiscible with water
- used to protect skin and emollient effects
examples of oleaginous bases
- regular and white petrolatum
- yellow and white ointment
absorption base properties
- able to absorb aqueous solutions to give w/o emulsion
- used for emollient effects
- difficult to wash off skin
examples of absorption bases
- hydrophilic petrolatum
- lanolin (wool fat)
water removable base properties
- also known as water washable
- external phase has to be water; o/w phase
example of water removable bases
hydrophilic ointment
greaseless base properties
- water soluble
- good for incorporating solid compounds
- soften with addition of water
example of greaseless bases
PEG ointment
What does PEG stand for and what are its other names?
- Polyethylene glycol
- PEO (polyethylene oxide)
- POE (polyoxy ethylene)
What are the ways in which you can prepare ointments?
- incorporation method
- fusion method (melt)
What materials can you use for the incorporation method?
- pill tile
- parchment paper
- unguator
- mortar and pestle
What is an unguator?
- electronic mortar and pestle
- equipment that goes inside the ointment jar an into the machine consists of a shaft and a blade
Define levigation
triturating a powder in an insoluble solvent
What are examples of levigating agents?
- mineral oil for oil phases
- glycerin for water phases
What are the steps to the incorporation method?
- incorporate drug into absorption base
- incorporate absorption base into oleaginous base
What is one thing to note when mixing ingredients in the fusion method?
mix the excipients with the highest melting point first
What are products that you HAVE to use fusion method for?
- beeswax
- paraffin
- stearyl alcohol
- PEG with high molecular weight
What are things to consider when selecting the appropriate bases?
- release rate of drug from semi-solid
- desirability of topical or percutaneous drug absorption
- desirability of occulsion of moisture from the skin
- stability of drug in base
- contact time to skin
- which part of the body it’s being applied to
What are dosage forms of semi-solids?
- ointments
- creams
- gels
- pastes
What does the # following PEG indicate?
the average molecular weight
PEG physical state with respect to molecular weight
- lower mw are liquid; higher mw are solids
- 200-600 transprent liquid
- 600-1000 semi-solid
- > 1000 solid
What materials can you use for the fusion method?
- small sacle: porcelain dish, glass beaker
- large sacle: large steam jacketed kettles
Common infections occur via which bacteria?
- Staphylococcus aureus
- Pseudomonas aeroginosa
The gram +/- terms were named after who?
Hans Christian Gram
Example of USP test for semi-solids
- minimum-fill
- microbial content
- packaging
- storage
- labeling
Properties of ophthalmic preparations
- diameter should be < 50microm
- sterile
Examples of preservatives
- paraben
- phenols
- benzoic acid
- sorbic acid
- quaternary ammonia compounds
- benzalkonium chloride
Properties of creams
- emulsions (usually o/w but can be w/o)
- can be easily washed off skin
- opaque
- once applied on skin, water evaporates and leaves behind a thin layer
Properties of gels
- aka jellies
- thixotropic
- must have gelling agent
Examples of gelling agents
- cabomer 940
- natural gums (tragacanth)
- cellulose derivatives ex:
- sodium carboxymethylcellulose
- HPMC
- carboxymethylcellulose
Properties of pastes
- must contain at least 20% of solid content
- able to absorb serous fluid
What are plasters used for?
to remove corn
What can glycerogelatin be used for?
varicose ulcer
TDD
- transdermal drug delivery
- aka percutaneous absorption
- absorb into system via skin
scopolamine
- approved by FDA 1979
- first TDDS approved
nitroglycerine
- aka trinitroglycerine
- used in angina pectoris and CHF
- releases NO (vasodilator)
clonidine
used for HTN
nicotine
used for smoking cessation
applications of creams
- topical skin products
- rectal and vaginal
properties of jars
- clear opaque glass
- plastic
properties of tubes
- aluminum
- plastic
aluminum tubes
coated with epoxy resin or vinyl to eliminate any interactions between tube and content
plastic tubes
made of high and/or low density polyethylene
What is a crimping clip?
a clip to seal off the end of a metal ointment tube
properties of skin
- in adult, covers 2m2
- weighs 11 lbs
- receives 1/3rd of blood circulation
- avoid first pass metabolism
anatomy of skin
- epidermis (outer layer)
- dermis (deeper layer)
properties of epidermis
- epithelial tissue
- semi-permeable membrane
- contain 90% keratinocytes and 8% melanocytes
properties of dermis
- strong connective tissue
- collagen and elastic fibers
How does drug molecule penetrate the skin?
via passive diffusion
layers of epidermis
- stratum corneum
- stratum lucidum
- stratum granulosum
- stratum spinosum
- stratum germinativum / basale
Rotigotine
- used in parkinson
- brand name: Neupro
Rivastigmine
- anticholinesterase
- used for Alzhiemers
- brand name: Exelon
stratum corneum
rate limiting step for drug absorption
subq
- hypodermis; not part of the skin
What are the properties that influence transdermal absorption?
- physico-chemical properties
- drug concentration
- site of absorption
- hydration status
- time of contact
- race
- individual variation: disease state, genetic, age, etc.
What are the types of physico-chemical properties?
- molecular weight
- solubility; part. coeff. of 1 preferred
- dissociation constant
nature of carrier
What are the categories of enhancers for skin absorption?
- chemical
- iontophoresis
- electroporation
- sonophoresis
What are other names for chemical enhancers?
- absorption promoter / enhancer
- permeation promoter / enhance
chemical enhancers
- reducing resistance in s. corneum
- causes temporary opening of tight junctions
What are things to consider when selecting a chemical enhancer?
- physico-chemical properties
- compatibility with formulation
- toxicity to s. corneum
Examples of chemical enhancers
- dimethyl sulfoxide (DMSO)
- azone
- acetone
- oleic acid
- propylene glycol
- sodium dodecyl sulfate
- sodium lauryl sulfate
iontophoresis
- electric current of 12-20v applied
- increase permeability of skin
- creates ion-electric field interaction -> directional force drives ion through skin
- facilitates deep penetration
Examples of iontophoresis
- lidocaine drugs being investigated for this kind of delivery: - dexamethason - amino acids - peptides - verapamil - propranolol
What are qualities of drugs for iontophoresis?
any drug, as long as it’s ionizable
What can be used to treat hyperhidrosis?
- hyperhidrosis = excessive sweating
- iontophoresis
electroporation
- electric current of 200-1000v applied for millisecond
- increases size of pores
- increases permeability up to four times
- has been used to deliver drugs with mw of several kDaltons
What is another name for electroporation?
electropermeability
What is another name for sonophoresis?
phonophoresis
sonophoresis
application of high frequency ultrasound
For transdermal drug delivery, what are ultrasounds used with?
coupling agent (gel, cream, etc) that transfers US energy from US transducer to skin
examples of drug permeation testing systems
- side-by-side diffusion cell (not used for human skin)
- Franz diffusion cell (top-to-bottom diffusion; take gravity into account)
What are the components of TDDS?
- adhesive
- backing layer
- frontal layer
What is the backing layer made of?
Aluminum (but doesn’t have to be)
monolithic system and examples
- drug and polymer mixed together
- Nitro-dur, Vivelle dot, Testoderm
membrane-controlled system and examples
- drug and polymer are in separate compartments
- can use liquid and semi-solids
- TrasdermNitro, Transderm-Scop
What are the barriers to ocular drug retention?
- nascolacrimal duct
- tear turnover
- conjunctival uptake
What is the nasolacrimal duct?
- connection between eye and nose
- drugs can be cleared through this
On average, how much fluid is there in the eye?
7-9 microL
How much displacement of fluid can a drop of fluid give in the eye?
- 50 microL
- ideal is 10-15 but there isn’t a dropper that can deliver that
List categories of ocular drugs
- anesthetics
- antibiotics
- antifungal
- anti-inflammatory
- antivirals
- astringents
- beta blockers
- miotics
- mydriatics
What are astringents formulations used for in the eye?
constrict blood; used in conjunctivitis
What are types of dosage ocular forms?
- solutions
- gel forming
- suspensions
- semi-solids
- inserts
- injections / implants
ocular solutions
- most common
- contains buffers, emulsifiers, preservatives, etc.
- short contact with eye
delivery vehicles for ocular solutions
- water
aq. mixtures of: - lower alkanols
- vegetable oils
- polyalkylene glycols
- petrolatum based jellies
What are examples of in-vitro apparatuses?
- skin cadaver
- synthetic skin
- synthetic polymers
- side-by-side diffusion chain / cells
- top-to-bottom cell
ex-vivo
take organ out of body
in-situ
procedure done in localized area
What are advantages of transdermal delivery?
- avoids first pass metabolism
- decreased drug-food interaction
- extended therapy with single application
- increased patient compliance
What are disadvantages of transdermal delivery?
- only potent drugs can be used
- developments of contact dermatitis
- irritation of skin
- expensive
polymers (all)
- cellulose derivatives (HEC, HPMC, NaCMC)
- acrylic acid
- PVA
- combinations: PVP-ethylcellulose
- gellan
- xanthum gum
- pluronics
With respect to ocular solutions, how can contact time between eye and solution increase?
addition of polymers
ocular gel-forming solutions
- gel + polymer
- once instilled in eye, gel is formed
- enhanced retention
What causes the geling formation in the eye when gel-forming solutions are applied?
- pH
- tear formation
- ionic strength
- temperature
- proteins
- components of tears
What is the temperature for the anterior portion of the eye?
34°C
What are the polymers used in gel-forming solutions?
- gellan
- xanthum gum
- carbomer
- pluronic
- CAP
- methyl cellulose
ocular suspensions
- must be > 10 microm to decrease irritation
- longer contact time that solution
- particles retained in cul-de-sac
ocular semisolids
- block vision - restricted to use at bedtime
- used often in children and post-operation
- longer contact time
What is used as the base in ophthalmic ointments?
mineral oil; mixture of white and liquid petrolatum
What polymers are used to develop ophthalmic gels?
- gellan
- xanthum gum
- carbomer
- pluronic
- CAP
- methyl cellulose
ocular inserts
- put insert in cul de sac
- designed to release drug slowly on zero order kinetics
ocular injections
- to reach posterior area
- intravitreal
- juxtascleral
- subconjunctival
- intrasclera
ocular implant
- planted in vitreous cavity
- releases drug over a certain period
- removed after therapy
What are things to consider with respect to ophthalmic preparations?
- sterility
- preservatives
- isotonicity
- buffer / pH
sterilization techniques
- moist heat under pressure
- dry heat
- filtration
- gas sterilization
- ionizing radiation
moist heat sterilization
- 121°C or 250°F
- 15 min
dry heat sterilization
- 160°C or 320°F
- 2 hours
filter sterilization
pores of filter are 0.2-0.7 microm
gas sterilization
ethylene oxide
preservatives for ocular drugs
- Quaternary ammonium compounds
- Oxidizing agents
- Organic mercurials
- Para-hydroxy benzoic acid esters
- Substituted alcohols and phenols
body’s physiological tonicity
- 0.9% NaCl
- 290mOsm
- 1.9% boric acid
What type of solution is used to treat corneal edema?
hypertonic
What is normal tear fluid pH?
- 4
- can tolerate pH change better than we anticipate
What is the composition of buffers?
usually weak acid + conjugate base
Besides resistance in pH change, what else does buffers do?
stabilize drug
What are the types of contact lenses?
- hard
- soft
- rigid gas permeable
hard contact lenses
- not permeable
- offer clarity and crisp vision
- only cover cornea
- diameter of 7-10microm
- made of PMMA
soft contact lenses
- not permeable
- softer and pliable
- not as clear
- diameter of 13-15microm
- made of HEMA
rigid glass permeable (RGP)
- permeable
- provide visual clarity
What are the types of care products for contact lenses?
- wetting solutions
- cleaning solutions
- disinfectants
- soaking and storage solutions
wetting solutions: contact lenses
- cellulose derivatives
- polyvinyl pyrrolidone
- polyvinyl alcohol
cleaning solutions: contact lenses
- surfactants
- enzymes
disinfectants: contact lenses
- hydrogen peroxide
- polyquad
soaking and storage solutions: contact lenses
- chlorhexidine
- benzalkonium chloride
What are the types of suppositories?
- rectal
- vaginal
- urethral (less common)
What kind of effects are suppositories used for?
- local
- systemic (less common)
properties of rectal suppositories
- adults weigh 2g, pediatrics weigh 1g
- 1.5 in long
- cylindrical
What are the systemic drug uses for rectal suppositories?
- sedatives
- tranquilizers
- nausea
- analgesics
What is another name for vaginal suppositories?
pessaries
properties of vaginal suppositories
- weigh 5g
- oviform of globular shaped
- sometimes needs applicator
- mostly used for local effects
What are the most common pathogens to the vaginal tracts?
- Trichomonas vaginalis
- Candida albicans
- Gardnerella vaginalis
properties of vaginal inserts
- ovoid shaped tablets
- must be administered with inserter
- disintegrated inside the vagina
What is another name for urethral suppositories?
bougies
properties of urethral suppositories
- cylindrical slender shape
- males: 5mm diam, 125mm length
- females: 5mm diam, 50mm length
- ## need applicator
What are urethral suppositories usually used for?
local anesthetic for examination
What are the types of suppository bases?
- cocoa butter and other fatty bases
- water-soluble or water-dispersible bases
- hydrogels
What are ideal properties of a suppository base?
- non-irritating to mucous membranes
- compatible with a variety of drugs
- melts, dissolves, or swells in rectal/vaginal fluids
- should not interfere with release or absorption of drug substances
cocoa butter and other fatty bases properties
- naturally occurring triglyceride
- melts at body temperature
- smooth; lubricant not needed
- exhibits polymorphism
What are substitutes to cocoa butter?
- hydrated fat
- hydrogenated regular oil
- suffer polymorph but have potential for lower rancidity
What are the polymorphs for cocoa butter?
- α melt at 18°C
- β melt at 37°C
- γ melt at 22°C
- melting temp. should not exceed 60°C or it will polymorph from β to α
What is another name for cocoa butter?
theobroma oil
water-soluble or water-dispersible bases properties
- dissolves / solubulizes
- offer prolonged release of drug
- can be stored at room temperature
- contain PEG or glycerinated gelatin
hydrogels properties
- swelling mechanism (via polymer)
- drug comes out of polymer
examples of hydrogel polymers
- polyvinyl alcohol (PVA)
- hydroxyethyl methacrylate
- polyacrylic acid
- polyoxyethylene
What are the ways in which you can prepare suppositories?
- rolling (hand-shaping)
- compression
- molding (fusion)
How should glycerinated gelatin suppositories be stored?
packaged tightly closed in screw-capped containers and stored at room temperature
What are the uses for otic drug preparations?
- ear infections
- inflammation
- pain
- removal of cerumen
- local only; no systemic
What makes up the outer ear?
- pinna
- external auditory canal
- tympanic membrane
What makes up the middle ear?
- auditory ossicles
- air-filled cavity in ear drum
What makes up the inner ear?
- chochlea
- vestibule and semi-circular canals
What are formulations of otic drugs?
- solutions
- suspensions
- semi-solids
What is used as the traditional method to soften cerumen for removal?
- light mineral oil
- vegetable oil
- hydrogen peroxide
What is the active ingredient for products to soften cerumen?
cabamide peroxide which releases oxygen to disrupt integrity of impacted wax
