CH 17 -- Special Solutions (pt 1) Flashcards
drugs are applied to the eye for….
the LOCALIZED effect of the medication on either the surface of the eye or its interior
name the dosage forms of opthalmic drug delivery
-aqueous solutions
-suspensions
-ointments
-inserts
what is the first choice of dosage form for the eyes?
aqueous solutions (aka drops)
for a medicine dropper, 1mL = __drops
20 drops
what are SIX disadvantages of ophthalmic solutions
-loss of instilled medication
-removal by the naso-lacrimal system
-short retention time on the eye surface
-frequent administration
-therefore: patient inconvenience and noncompliance
-low bioavailability
1 disadvantage of ophthalamic solutions:
“loss of medication using regular eye droppers”
Explain this.
for a regular eye dropper, 1mL = 20drops.
therefore, 1 drop=50 microliters
our blinking eyes can only hold 10 microliters. Therefore, 40 microliters are being wasted. This is an 80% loss
our normal tear volume is ___ microliters.
if not, you have ___ syndrome
7 microliters
dry eye syndrome
eyes that are NOT blinking can hold up to ___ microliters.
but when blinked, it can only retain ___ microliters
non blinking eye can hold up to 30 microliters
but when blinked, it can only retain about 10 microliters
our tears are produced where?
the lacrimal gland
a problem with ophthalmic solutions:
Removal by the naso-lacrimal system.
explain this further
when reflex tearing causes volume greater than 7-10 microliters, the drug undergoes superficial adsorption through the conjunctiva. this causes a rapid removal by peripheral blood vessels and eventually goes to the GI tract.
this causes a potential SYSTEMIC EFFECT. we don;t want this. the purpose of ophthalmic delivery is for local effects either on the surface or interior of the eye. this can cause side effect
what is a method to avoid systemic absorption of the active ingredient(s) that results from the drainage of the drug through the nasolacrimal duct and then swallowed?
by applying gentle pressure to the lacrimal sac for 3-5mins after administration
why is there such a short retention time of ophthalmic solutions on the eye?
because the eye surface is very small, and we blink and cry when something is applied to the eye.
due to this, eyedrops require frequent administration which is another disadvantage
ophthalmic solutions have low bioavailability. give an example and explain why this isn’t a huge problem and therapeutic effects can still exist
pilocarpine ophthalmic solution has <1% bioavailability
however, therapeutic effects still exist because we only want local effects. the drops are being applied right at the receptor site
name 2 methods to enhance bioavailability of ophthalmic solutions
greater drug concentration (most ophthalamic solutions have a HIGH concentration)
OR
increase corneal contact time (5 diff dosage forms) one example: mucoadhesive polymers, adsorbable gelatin sponge
how do you calculate the effective “dose” of ophthalmic solution actually applied?
-strength of dose administered
-volume administered
-retention time of the drug on the surface of the eye
-frequency of administration
when considering the “volume administered” in calculating the effective dose of an ophthalmic solution, what should you keep in mind?
each drop is 50 microliters BUT the eye can only hold 10microliters. 40 microliter loss (80%)
name 7 pharmaceutical requirements in the preparing of solutions and suspensions for ophthalmic use
-sterility and preservation
-isotonicity value
-buffering
-viscosity and thickening agents
-OCULAR bioavailabiliy
-additional considerations
-packaging
which 2 dosage forms MUST be sterile
parenteral and ophthalmic
the greater the retention time, the ___ the absorption
better
name 2 methods for sterilization
autoclaving and membrane filtration
WHY is preservation needed for ophthalmic products?
the packaging is “multiple dose” meaning that the patient will be using it many times after it has been opened
syrup preservative is mainly used against ____ while ophthalmic preservative is mainly to combat ____
syrup – mainly fungi
ophthalmic – mainly bacteria
paraben group preservatives are against ___ and NOT ___
against FUNGI and NOT bacteria
for preservative for ophthalamic solutions, when would you want to use the ionized form of a preservative and when would you want to use the unionized form?
ionized — longer duration
unionized – more effective (can cross cell membrane)
name all 6 preservatives for ophthalmic products and whether they are ionized or unionized
benzalkonium chloride – ionized
benzethonium chloride – ionized
chlorobutanol – unionized
phenylmercuric acetate - unionized
phenylmercuric nitrite – unionized
thimerosal – ionized
what is the name of the bacteria that CANNOT be in the eyes or it will cause loss of vision and is not destroyed by the aforementioned 6 preservatives
Pseudomonas aeruginosa
are parabens used as a preservative in ophthalmic preparations? explain
NO. paraben groups are for FUNGI and not bacteria
isotonicity related to ophthalmic preparations is important to ensure ____
comfort when the solution/suspension is applied to the eye
name 2 osmolarity-adjusting agents
NaCl (0.7-1.5%)
mannitol
which does the eye tolerate better — hypotonic solutions are hypertonic solutions
hypertonic. this is so because the discomfort is only TEMPORARY – our tears will dilute the hypertonic solution which will bring it lower.
body fluids, INCLUDING BLOOD AND TEARS, have an osmotic pressure corresponding to that of a ___% solution of sodium chloride
0.9%
when are eye solutions said to be isotonic
when OUR osmotic pressure is the same as the SOLUTION APPLIED
when the particles are UNCHARGED (as with sucrose), osmotic pressure depends solely on….
the number of molecules present
When the particle is an ELECTROLYTE (as in sodium chloride), the number of particles that it contributes to the solution will depend on…..
the concentration of the molecules present and ALSO the degree of ionization
what is the difference between “isotonic” and “iso-osmotic”
often used interchangeably, but isotonic is correctly used only when referring to a specific body fluid.
Iso-osmotic is a term comparing the osmotic pressure of 2 liquids that may or may not be physiological fluids
sulfacetamide sodium solution
what is the isotonic equivalency?
what is the therapeutic drug concentration?
isotonic equivalency = 3.5%
therapeutic drug concentration = 10-30%
therefore, some irritation for this product is unavoidable. therapeutic effect is more important than isotonicity
ophthalmic products should have a pH of about ____. acceptable formulation range is __ to ___
7.4
6-8
name the PURPOSES of buffering (4)
-greater comfort to the eye
-render the formulation more stable
-enhance the bioavailability of the drug
-maximize preservative efficiency
to enhance the bioavailability of an ophthalmic preparation via buffering, what molecular species should be favored? (ionized or unionized)
unionized
moat drugs used ophthalmically are weakly ____and have weak buffer capacity.
Therefore, the eye can tolerate a greater deviation from physiological pH (7.4) toward ____ than toward the ___ range
weakly acidic
better tolerate alkalinity than toward the acidic range
for MAXIMUM comfort, the pH should be 7.4.
However, what is the issue with this?
7.4 is not pharmaceutically possible, because at 7.4 pH many drugs are insoluble in water
what are 3 examples of buffer salts?
they are selected based on what?
phosphate, borate, and citrate
things to consider:
-their compatibility with the drug and with other components of the preparation
-the target pH should be one at which there is greatest activity but ALSO maintaining stability
name 3 reasons to increase the viscosity of an ophthalmic preparation
-increases the retention time, reduces the drainage rate (no systemic effects), increases the OCULAR bioavailabilty
what can be used in ophthalmic preparations to increase viscosity? be specific
cellulose (fiber) derivatives:
-methylcellulose
-hydroxypropyl methylcellulose
PVA (polyvinyl alcohol) is used most often due to disadvantages of cellulose derivatives.
cellulose derivatives are insoluble in water and precipitate out, and thus form crust and transient blurring
is polyvinyl alcohol water soluble? what is it used for?
yes
used in ophthalmic preparations to increase viscosity, and thus increase retention time, reduce drainage rate, and increase ocular bioavailabilty
most ophthalmic solutions are packaged in….
plastic dropper bottles with a fixed, built in dropper
5, 15, and 30mL are standard volumes
what are plastic drop-trainer bottles made of and why?
LDPE (low-density polyethylene)
makes it easier to squeeze the bottle to get a drop out.
if it was high density, it would be hard to squeeze
what is the problem with using a plastic dropper bottle?
if solution has very small molecules. permeability issue and sorption issue. – glass would be used instead
can plastic dropper bottles be made light resistant?
yes – with titanium dioxide
what is important about the tips and caps of a dropper bottle
tips and caps form a seal with the tip when tightly screwed on to avoid trapping oxygen inside which could potentially contain microorganisms
what is the area of the cornea
12mm (0.5 inches)
the vast majority of preparations intended for intranasal use contain ____ agents are are employed for their ____ activity on the nasal mucosa
adrenergic, decongestant
what are the dosage forms for nasal preparations
SOLUTIONS and JELLIES
Which has a higher (longer) retention time – jellies or solutions?
jellies
is isotonicity a concern in preparing nasal decongestant solutions?
yes – isotonic to the nasal fluids
why are nasal solutions buffered?
to maintain drug stability while approximating the normal pH range of the nasal fluids (5.5-6.5)
do nasal solutions need to be stabilized and preserved?
as needed
what are inhalants?
drugs or combos of drugs that, due to their high vapor pressure, can be carried by an air current into the nasal passage where they exert their effects
are inhalants used for local or systemic effects?
local and systemic
local action on the bronchial tree OR
systemic effects through absorption from the lungs
inhalations are ___ or ___ of ___ administered by the ___ or ___ respiratory route
DRUGS or SOLUTIONS OF DRUGS administered by the NASAL or ORAL respiratory rout
what are 2 commercially available products for inhalation?
nebulizer and vaporizer
explain what a vaporiser is
it is a heating system that vaporizes solutions of plain water and volatile oil (medication) and is inhaled by the pt.
humidifiers increase humidity
explain how nasal sprays should be used
clear nostrils, spray in UPRIGHT POSITION.
Spraying downward could give undesired systemic effects
are otic preparations used for local or systemic treatment
local
otic solutions only occupy which portion of the ear?
external acoustic meatus
name the 4 categories of otic preparations
-cerumen (earwax) removing solutions
-anti-infectives
-anti-inflammatory
-analgesic
name NINE agents used in otic drugs
- acetic acid
- aluminum acetate solution
- boric acid
- antipyrine
- camphor
- carbamide peroxide
- glycerin
- menthol
- olive oil
name the function of Acetic Acid in otic preparations
acetic acid is in anti-infective agent. also has anti-inflammatory and antipruritic action (itch relief)
has value against organisms that cause external otitis (these cannot grow at a low pH)
name the function of Aluminum Acetate solution in otic preparation
aka Burrow’s solution
fights infection by reducing pH of the external ear canal. also an astringent (shrinks body tissues to reduce bleeding)
what is the function of boric acid in otic preparations
VERY WEAK anti-infective properties – for external ear canal infections.
CONTRAINDICATED IN CHILDREN UNDER 12
between Acetic acid, aluminum acetate solution, antipyrine, and boric acid, which has weak action and which is a lot of action
lot of action = antipyrine. other 3 have weak action
name the function of antipyrine in otic preparations
anti-inflammatory and anesthetic
used to treat congestive and SERIOUS stages of acute otitis, also can facilitate removal of earwax
what is the function of camphor in otic preparations
-mild antipruritic and analgesic agent
-soothing and counterirritant. induces LOCAL vasoconstriction – mild decongestant effect
what is the function of Carbamide peroxide in otic preparations
ceruminolytic – softens cerumen for irrigation (removal)
what is an emmolient?
softens or soothes the skin (moisturizer)
what is the function of glycerin in otic preparations?
emmolient — softens earwax and maintains moisture
what is the function of menthol in otic preparations
SIMILAR TO CAMPHOR - counterirritant
-provides mild analges
what is the function of olive oil in otic preparations
it is an ingredient
-lubricant and emmolient properties.
-helps to soften cerumen (like carbamide peroxide)
does simple syrup contain preservatives?
no
what is the specific gravity of simple syrup
1.313
simple syrup contains ___ of sucrose
85%w.v
does Syrup NF contain alcohol
no
remember: contains 85g sucrose and purified water QS to 100mL
name the components of Iodine Tincture USP
Iodine 2g
Sodium Iodine 2.4g
Alcohol 50mL
Purified Water, to make 100mL
Chlorobutanol is used in ophthalmic solutions to do what?
preservative
what are the viscosity builders in ophthalamic preparations?
methylcellulose
hydroxypropyl methylcellulose
polyvinyl alcohol
drugs administered by inhalation can be….
bronchodilator
decongestant
anti-inflammatory
