Dosage Forms Exam 3 Ophthalmic

Front 1

You may give injections to patients to the subconjunctival and intraocular tissues, why would you want to do this?

Back 1

For faster and higher ocular drug delivery

Front 2

The eye consists of 3 __________ layers.

Back 2

concentric

Front 3

The outermost concentric layer of the eye consists of what?

Back 3

conjuctiva/sclera and cornea

Front 4

The middle concentric layer of the eye consists of what?

Back 4

Uveal tract
(choroid, ciliary body, and iris)

Front 5

The innermost concentric layer of the eye consists of what?

Back 5

retina

Front 6

What is the dominant route (structure) a drug will get into the eye?

Back 6

cornea

Front 7

What parts of the eye are located in front of the iris and pupil?

Back 7

cornea
anterior chamber

Front 8

What are the upper and lower eyelids (inside part) called?

Back 8

upper: conjuctival epithelium
lower: conjuctival sac

Front 9

What parts of the eye are located behind the iris and pupil?

Back 9

posterior chamber
lens

Front 10

The inside of the eye is divided by the lens into what 2 things?

Back 10

aqueous and vitreous humors/segments

Front 11

The aqueous chamber is divided by the iris into what 2 things?

Back 11

anterior and posterior chambers

Front 12

The _______ ______ is divided by the iris into anterior and posterior chambers.

Back 12

aqueous humor

Front 13

What part of the eye must a drug reach?

Back 13

the anterior and posterior chambers of the aqueous humor

Front 14

The inside of the eye is divided by the lens into the aqueous and vitreous humor, of these 2 humors, which one recieves most of the drug?

Back 14

Aqueous humor

Front 15

The aqueous humor is divided by the ______ into the anterior and posterior chambers.

Back 15

iris

Front 16

The inside of the eye is divided by the _____ into aqueous and vitreous humors/segments.

Back 16

lens

Front 17

Aqueous humor is continually generated by the __a____ __a____ and flows from the __b_____ ___b___ through the __c____.

Back 17

a) ciliary bodies

b) posterior chamber

c) pupil

Front 18

The aqueous humor exits into systemic circulation mainly through what canal?

Back 18

Schlemm's canal

Front 19

____________ is a thin transparent, vascularized mucous membrane that extends from the edge of the cornea, across a portion of the sclera, then extends to the internal surface of the eyelids to form the "cul-de-sacs".

Back 19

Conjunctiva

Front 20

__________ is the gland responsible for tear production.

Back 20

Lacrimal gland

Front 21

T/F? The conjuctiva is a thin, transparant mucous membrane that extends from the edge of the lens across the portion of the iris, then extends to the internal surface of the anterior chamber to form the conjuctival sacs.

Back 21

FALSE
goes from edge of cornea
across a portion of the sclera
then extends to internal surface of the eyelids

Front 22

The conjuctiva is a thin transparent, vascularized mucous membrane that extends from the edge of the cornea, across a portion of the sclera, then extends to the internal surface of the eyelids to form the ___________ ________.

Back 22

conjuctival sacs (cul-de-sacs)

Front 23

What is the purpose of having tears form?

Back 23

to remove foreign materials

Front 24

What is the name of the small opening to the lacrimal canaliculi, it is located in the very corner of your eye nest to the bridge of your nose?

Back 24

Puncta

Front 25

The punca is the small opening to the _______ _________, that's located in the very corner of your eye nest to the bridge of your nose

Back 25

lacrimal caniculi

Front 26

What is the name of the drainage system for the lacrimal fluid?

Back 26

Nasolacrimal apparatus

Front 27

Tears drain through the ____a____ to the ___b___ __b__ then to the nasal cavity via the ___c___ __c__, from the nasal cavity they are removed towards the ____d_____.

Back 27

a) canaliculi
b) lacrimal sac
c) lacrimal duct
d) nasopharynx

Front 28

Tear drainage occurs by _______ and through an active process employing a mechanism, what mechanism are they referring to?

Back 28

gravity

blinking

Front 29

The major pathways for a topical ophthalmic to reach intraocular tissues are through the cornea and the sclera, of those 2 pathways which one predominates?

Back 29

cornea
(sclera's not as easy to get thru)

Front 30

The _________ is a complex, optically transparent tissue and is covered by a tear film.

Back 30

cornea

Front 31

What are the 3 layers that make up the tear film before you reach the epithelium?

Back 31

Mucoid layer
Tear fluid
Lipid layer

Front 32

Of those 3 tear film layers, which one is involved in the adhesion of the aqueous tear fluid, and keeps the cornea wettable?

Back 32

Mucoid layer

Front 33

T/F?
The mucoid layer is involved in the adhesion of the aqueous tear fluid, and keeps the sclera wettable.

Back 33

FALSE
keeps the CORNEA wettable

Front 34

What is the tear film layer of aqueous solution of inorganic electrolytes, proteins, and glucose called?

Back 34

tear fluid

Front 35

What tear film layer reduces evaporation of the tear fluid?

Back 35

lipid film

Front 36

the lipid film of the tear film layer of the eye is made up of what?

Back 36

wax & cholesterol esters
(adsorbed to the tear fluid)

Front 37

The tear layer is an aqueous solution of electrolytes, proteins, and glucose. What type of proteins do they possess? (think of the fact that tears help kill or keep out foreign invaders)

Back 37

Enzymes and immunoglobulins

Front 38

The concentration of drug in which the tear film provides a driving force for what?

Back 38

passive diffusion through the cornea

Front 39

T/F?
Corneal permeation dominates over passive diffusion through the cornea.

Back 39

FALSE
(passive diffusion thru the cornea dominates over corneal permeation)

Front 40

What are the 3 layers of the cornea that precede the aqueous humor?

Back 40

epithelium,
stroma,
and the endothelium

Front 41

What layer of the cornea has squamous cells on the surface that are surrounded by tight junctions & microvilli, and is continuous with the conjunctiva, and is stratified?

Back 41

Epithelium

Front 42

Describe the epithelium of the cornea.

Back 42

-continuous with the conjunctiva, but w/ a different thickness
-stratified epithelium w/ squamous cells on the surface surrounded by tight junctions and have microvilli
-enzymes are present

Front 43

What is the purpose of the microvilli on the squamous cells of the corneal epithelium?

Back 43

To increase surface area

Front 44

The corneal epithelium layer is ___________ (lipophilic/hydrophilic).

Back 44

lipophilic
(lipophilic drugs will permeate well!)

Front 45

If the corneal epithelium is lipophilic, what ionization state should the drug be in?

Back 45

unionized

Front 46

The corneal epithelium has enzymes present, what can these enzymes do?

What kinds of enzymes are present?

Back 46

metabolize some drugs

esterases, peptidases, and proteases

Front 47

The _____ (layer) of the cornea is mostly water and is a barrier for lipophilic drugs.

Back 47

stroma

Front 48

The stroma of the cornea is about ___ thin lamella, each composed of _______ fibers.

Back 48

60

collagen

Front 49

T/F?
The corneal endothelium is double cell layer that provides metabolic exchange between the cornea and the aqueous humor.

Back 49

False, it is a single layer

Front 50

T/F?
The endothelium is more permeable than the epithelium.

Back 50

true
(up to 200x more permeable)

Front 51

T/F?
Before the cornea is crossed, most of the drug will be lost. Normally less than 10% of the dose will transverse the cornea.

Back 51

False, less than 5%

Front 52

What kinds of drugs are best absorbed in the eye?
a) drugs with low octanol/water partition coef. at physiological pH
b) drugs with moderate octanol/water partition coef. at physiological pH
c) drugs with high octanol/water partition coef. at physiological pH

Back 52

b) drugs with MODERATE octanol/water partition at physiological pH
B/C OF DIVERSE BARRIERS!

Front 53

T/F? The less the concentration in the tear film, the faster the penetration.

Back 53

false
the GREATER the conc...the faster

Front 54

Greater absorption occurs through _________ epithelium.

Back 54

damaged

Front 55

The time to peak aqueous humor concentrations often range between ___-___min

Back 55

20-60min

Front 56

Before crossing the cornea, applied drug can be removed from the surface of the eye by ____a_____ and by the _____b_____ ____b_____.

Back 56

a) spillage

B) nasolacrimal drainage

Front 57

T/F?
An eyedrop can range from 25-56 microliters (~40 microliters) and a tear drop is about the same.

Back 57

false
a tear drop is only 7 microliters

Front 58

What are the possible fates of an eye drop before it crosses the cornea?

Back 58

1) spillage

2) removal by nasolacrimal drainage

3) enzymatic degradation

4) conjuctival permeation followed by absorption

Front 59

What's the volume that can be momentarily accommodated in the lower cul-de-sac without spillage?

Instilling more drops would lead to what?

Back 59

30 microliters

immediate loss

Front 60

Blinking increases the spillage and facilitates removal by the what?

Back 60

nasolacrimal apparatus

Front 61

What 2 thing force fluid through the puncta to the nasolacrimal apparatus?

Back 61

gravity and the
blink pumping apparatus

Front 62

What are the possible fates of an eye drug after crossing the cornea?

Back 62

1) penetration into deeper intraocular tissues

2) binding to proteins

3) elimination

Front 63

Regarding the fate of a drug thru penetration into deeper intraocular tissues of the eye, the greatest concentrations are usually achieved where?

Back 63

within the aqueous humor in the aqueous region of the eye.

Front 64

The concentration of drug within the anterior chamber will be less than in the applied product. How much less?

Back 64

often 2 orders of magnitude
(1 order=50...so 100x less)

Front 65

T/F?
The amount reaching the posterior region is usually significant. Treating posterior region problems is typically achievable with a topical product.

Back 65

FALSE
usually insignificant and cannot be achieved

Front 66

Regarding the fate of a drug after crossing the cornea due to it binding to proteins, some lipophilic drugs can bind to what?

Back 66

melanin in the iris

can also bind to proteins in tears and within the cornea

Front 67

Melanin in the iris (in dark irides) can bind to certain lipophilic drugs and can ______ the drug effect or act as a ________.

Back 67

reduce

depot

Front 68

Regarding the elimination of a drug after crossing the cornea, drugs can enter the systemic circulation from within the eye via what 2 things?

Back 68

1) via aqueous humor turnover (thru the Canal of Schlemm)

2) through uveal blood vessels

Front 69

Regarding topical opthalmics, systemic absorption can be significant.
What are the 2 routes of systemic absorption?

Back 69

1) absorption thru tissues encountered following nasolacrimal drainage

2) absorption through blood vessels in the conjunctiva

Front 70

A significant fraction of a topical ophthalmic drug can be systemically absorbed in the ______ _______.

What are some other tissues that can contribute to systemic absorption?

Back 70

nasal cavity


lacrimal sac
nasopharynx
cheeks
GI tract

Front 71

Why would the GI tract be a possible way a topical ophthalmic drug can be systemically absorbed?

Back 71

because we swallow some

Front 72

The conjunctiva is more permeable than the cornea covers a much greater surface area, therefore it ________ drug absorption.

Back 72

facilitates

Front 73

How can a drug get absorbed systemically by the conjunctiva?

Back 73

it's highly vascularized and most of the drug that permeates is absorbed systemically

Front 74

Overall what percent of the drug instilled in the eyes can be systemically absorbed?

Back 74

50%

Front 75

Sterility is required for ophthalmics, what organism is of great concern because it can invade the cornea causing corneal ulceration and blindness?

Back 75

Pseudomonas aeruginosa

Front 76

There are ____ sterility tests used to cover all organisms that can invade eyedrops.

Back 76

USP

Front 77

What is the most widely used antimicrobial preservative?

What is it effective against?

Back 77

BAC- benzalkonium chloride

Pseudomonas aeruginosa

Front 78

What is a pro and con to using BAC?

Back 78

pro: can affect corneal penetration (acts as a penetration enhancer)

con: can damage the corneal epithelium if the concentration is too high

Front 79

Besides BAC, what are some other antimicrobial preservative excipients in eyedrops?

Back 79

Polyquad (polyquaternium-1)

Thimerosal (0.001-0.01%)

oxidants (Purite)

Front 80

What's an alternative to BAC?

Why is it used?

What's the downfall of using this?

Back 80

-Polyquad (polyquaternium-1)

-it's almost nonsensitizing

-doesn't penetrate the cornea well.

Front 81

If you see Thimerosal in the ingredients of an eyedrop, what would you say it's used for? What's a downfall of this excipient?

Back 81

an antimicrobial preservative

it's an organic mercurial, so hypersensitivity is a problem

Front 82

Which excipient is NOT for antimicrobial preservation?
a) polyvinyl alcohol
b) polquaternium-1
c) oxidant
d) Thimerosal

Back 82

a) polyvinyl alcohol
(viscosity modifier)

Front 83

What kind of eyedrops need antimicrobial preservative excipients?

Back 83

multi-dose eyedrops

Front 84

What's the normal pH of tears?

Back 84

7-7.4

Front 85

What antimicrobial preservative is an organic mercurial and has a hypersensitivity problem?

Back 85

Thimerosal

Front 86

Solutions with a pH below __a__ or above __b__ have been associated with what?

Why wouldn't you use these?

Back 86

below 6.6
above 9.0

-associated w/ irritation, reflex tears, and blinking
-speeds up elimination from eye surface

Front 87

T/F?
The tear film had a very broad buffer capacity.

Back 87

False

it has a very LIMITED buffer capacity

Front 88

The tear film has a very limited buffer capacity. Therefore, the instilled fluid will control pH for how long?

Back 88

several minutes

Front 89

What are some examples of buffer excipients used in eyedrops?

Back 89

acetate
borate
citrate
phosphate

Front 90

What's often added to eyedrops to adjust pH?

Back 90

strong acids (HCl or H2SO4)
or strong bases (NaOH)

Front 91

If you see HCl or H2SO4 in the ingredients of an eyedrop, what's it most likely in there for?

Back 91

to adjust pH--these are strong acids

Front 92

If you see NaOH in the ingredients of an eyedrop, what's it most likely in there for?

Back 92

to adjust pH--this is strong base

Front 93

How would you chose a certain buffer to add to an eyedrop?

Back 93

-base it on the compatibility w/ the drug and on desired pH.

-often chosen to help solubilize or stabilize the drug

Front 94

What's the normal osmolarity of tears?

Back 94

302-318 mOsm/kg

Front 95

__________ is very important for comfort. Instilled fluids far outside of the normal range can irritate, leading to what?

Back 95

Isotonicity

reflex tearing and blinking,
speeding up drug elimination from the eye surface

Front 96

What are important excipients used to bring up osmolarity in eyedrops?

Back 96

tonicity modifiers

Front 97

What are the most common tonicity modifiers?

Back 97

dextrose
Mannitol
NaCl

Front 98

Increased viscosity can increase ___a_____ ____ and reduce ____b____ ____, which increases ____c_______.

Back 98

a) retention time
b) drainage rate
c) bioavailability

Front 99

What happens if viscosity is too high in an eyedrop?

Back 99

it can cause irritation

Front 100

Which of the following is NOT a viscosity modifier?
a) glycerin
b) dextrose
c) hydroxyethylcellulose
d) polyvinyl alcohol
e) PEGS
f) these are all viscosity modifiers

Back 100

b) dextrose (tonicity modifier)

Front 101

Viscosity modifiers have a __________ effect and are used in what kinds of products?

Back 101

lubricating

artificial tears

Front 102

What is a potential problem to using viscosity modifiers in eyedrops?

Back 102

may cause crust formation and transient blurring

Front 103

Which is used more: solutions or suspension?

Back 103

solutions

Front 104

When formulating and manufacturing solutions, how do you sterilize it?

Back 104

by heat or membrane filtration

Front 105

When formulating and manufacturing suspensions, you must reduce particle size to what?

Back 105

less than 10 micrometers

Front 106

Why must you reduce particle size in a suspension?

Back 106

-reduce irritation
-speed dissolution

Front 107

Why can't you filter-sterilize suspensions?

How do you make sure it's sterilized then?

Back 107

-will remove drug particles

-aseptically add the sterilized solid to the sterilized solution

Front 108

Why would you use a suspension instead of a solution?

Back 108

-if you have a poorly water-soluble drug
-to improve stability

Front 109

What's a pro and con to using a suspension?

Back 109

pro: mix with tears less rapidly & remains in the cul-de-sac longer

con: doesn't provide a drug depot

Front 110

Which of the following is an antioxidant used in eyedrops?
a) borate
b) polysorbate 80
c) polyvinyl alcohol
d) EDTA disodium
e) sodium metabisulfite

Back 110

e) sodium metabisulfite

-borate (buffer)
-polysorbate 80 (surfactant)
-polyvinyl alcohol (viscosity modifier)
-EDTA disodium (chelator)

Front 111

Which of the following is a chelator in an eyedrop?
a) phosphate
b) EDTA disodium
c) Thimerosal
d) PEGS
e) Benzalkonium chloride

Back 111

b) EDTA disodium

-phosphate (buffer)
-Thimerosal (antimicrobial presrvative)
-PEGS (viscosity modifiers)
-Benzalkonium chloride (antimicrobial preservative)

Front 112

Besides its ability to limit oxidation by chelating metals, what is EDTA's other important function.

Back 112

increases the activity of BAC against P. aeruginosa

Front 113

What's an example of a surfactant in an eyedrop?
a) polyvinyl alcohol
b) citrate
c) glycerin
d) polysorbate (Tween) 80
e) mannitol

Back 113

d) polysorbate (Tween) 80

-polyvinyl alcohol (viscosity modifier)
-citrate (buffer)
-glycerin (viscosity modifier)
-mannitol (tonicity modifier)

Front 114

Why are surfactants used in eyedrops?

Back 114

used as wetting agents for suspensions and can facilitate spreading of the drops (reduce surface tension)

Front 115

Since the introduction of the __________, eyedrops are almost entirely packaged in dropper bottles.

Back 115

Drop-Tainer

Front 116

What are standard volumes of dropper bottles?

Back 116

5, 10, 15, and 30ml

Front 117

What are some semi-solid ophthalmics?

Back 117

ointments and gels

Front 118

What's the main advantage of using an eye ointment?

Back 118

prolonged contact time
(cleared as slowly as 0.5%/min)

Front 119

What's the main disadvantage of using an ointment?

Back 119

can cause blurred vision and matting of the eyelid

Front 120

What's the most common ointment base used in eye ointments?
Why is this used?

Back 120

-white petrolatum (with or without mineral oil)

-used to reduce viscosity

Front 121

How do you sterilize an eye ointment?

Back 121

by heat, then filter while molten

Front 122

Eye ointments are used frequently when?

Back 122

following surgery

Front 123

What's the standard tube size for an eye ointment?

Back 123

3.5gm

Front 124

An eye gel employs a gel former such as _______ or _____.

Back 124

Carbomer or gums

Front 125

What's an advantage to using an eye gel?

Back 125

prolongs contact time

Front 126

How long should you shake a suspension before use?
a) 5 sec
b) 10 sec
c) 15 sec
d) 20 sec
e) 30 sec

Back 126

b) 10 sec

Front 127

What fingers do you hold an eyedrop bottle container with?

Back 127

between thumb and middle finger, with index finger on the bottom of the vial

Front 128

How long should you keep your eye closed after dropping medicine in the conjunctival sac?

Back 128

30 seconds

Front 129

Why would you want to apply pressure to the inner corner of the eye for at least 30 seconds after instilling a drop?

Back 129

forms a nasolacrimal occlusion--it'll slow drainage as well as limit systemic effects

Front 130

T/F? You should rinse or wipe the dropper tip after using.

Back 130

false

Front 131

If you have to apply different eye medications (solns) in your eye, how long in between should you wait?

Back 131

5 minutes

Front 132

Should you apply fast-acting drops before long-acting? how long should you wait in between?

Back 132

yes
5min

Front 133

If you have to use an eyedrop and an eye ointment, which one should be applied first and how long should you wait in between?

Back 133

eyedrop first
wait 10 min

Front 134

Why shouldnt you apply eyedrops in eyes with contact lenses in?

Back 134

BAC can bind to contacts

Front 135

How long should you wait to discard eyedrop bottle?

Back 135

3 months after opening, but 30 days is often recommended.

Front 136

What fingers do you use to hold an eye ointment tube?

Back 136

hold tube between the thumb and forefinger of the opposite hand.
The remaining fingers should be braced against the cheek or nose

Front 137

How much of a ribbon of ointment do you normally use?

How long should you close your eye for after putting ribbon in?

Back 137

1/4 - 1/2 inch

1-2 minutes (and roll eye in all directions)