Ophthalmic and Nasal part 1 (7 concept 2 calcs) Flashcards by amanda kastel

*particle size limit for ophthalmic suspensions

10 micrometers

How well did you know this?

Not at all

Perfectly

*can ophthalmic suspensions be sterilized using filtration?

pore size is 0.22 micrometers. the particles cant pass - too large

How well did you know this?

Not at all

Perfectly

**name the 5 layers of the cornea from top to bottom and state whether lipophilic or hydrophilic

top - epithelium (lipophilic)
bowman’s membrane (too thin)
stroma (hydrophilic)
descemet’s membrane (too thin)
endothelium (lipophilic)

How well did you know this?

Not at all

Perfectly

**hydrophilic drug is to be administered through the eye.

what layer serves as the “barrer” and is thus the rate limiting step?

what about for a lipophilic drug?

crossing the EPITHELIUM

for a lipophilic drug, the STROMA is the barrier and rate limiting step

How well did you know this?

Not at all

Perfectly

what is the main pathway for permeation of drugs into intraocular tissues?

*what is it covered by?

the cornea

covered by a tear film

How well did you know this?

Not at all

Perfectly

*function of the tear film

covers the cornea and keeps it MOIST – provides lubrication

protects against infection, removes debris, and provides nutrients

How well did you know this?

Not at all

Perfectly

*what structure provides lubrication for the movement of the eyelids

the tear film

How well did you know this?

Not at all

Perfectly

*____ is involved in the adhesion of the aqueous phase to the cornea (wetting)

MUCIN

How well did you know this?

Not at all

Perfectly

***normal volume of tear fluid with blinking

7-10 micrometers

How well did you know this?

Not at all

Perfectly

*approximate pH of the tear fluid and osmolality

pH 7-8

300mOsmol/L

How well did you know this?

Not at all

Perfectly

the very top of the tear film has a ___ layer

LIPID layer - to protect the underlying aqueous layer

How well did you know this?

Not at all

Perfectly

which 2 components help to expel mucin into the tear film

the mucoid layer and microvilli

How well did you know this?

Not at all

Perfectly

**true or false

the conjunctiva is made up of connective tissue and is highly vascularized

FALSE - epithelial tissue and is highly vascularized - lot of blood vessels

How well did you know this?

Not at all

Perfectly

white part of the eye is called the….

sclera

How well did you know this?

Not at all

Perfectly

what is the sclera made of and what is its function

tough, fibrous tissue

covers the posterior segment of the eye - protects from physical damage

How well did you know this?

Not at all

Perfectly

*does the conjunctiva help to lubricate the eye?

YES - produces mucus and tears - also protects against microbes

How well did you know this?

Not at all

Perfectly

**under normal conditions, what is the tear volume in the conjunctival sac

7-10 microliters

How well did you know this?

Not at all

Perfectly

maximum volume the conjunctival sac can hold

30 microliters

How well did you know this?

Not at all

Perfectly

*commercial eye droppers typically deliver…..

25-50 microliters (avg 39) – more than the conjunctival sac can hold!

How well did you know this?

Not at all

Perfectly

as mentioned, commercial eye drops typically deliver MORE than what the conjunctival sac can even hold

what happens because of this?

rapid reflex blinking and tear secretion

How well did you know this?

Not at all

Perfectly

most of the instilled drug from an eye drop leaves though _____ and the excess is spilled where?

the lacrimal drainage system

excess spilled onto cheeks

How well did you know this?

Not at all

Perfectly

*for how long does the drug reside in the conjunctival sac

3-5 mins (then will drain)

How well did you know this?

Not at all

Perfectly

**what are the 2 pathways to get into ocular tissue

-corneal penetration

-conjunctiva-sclera pathway (non-corneal route)

How well did you know this?

Not at all

Perfectly

*which drugs typically go through the corneal route and which typically go through the conjunctiva-sclera route

cornea – small, low MW, lipophilic drugs

conjunctiva-sclera - hydrophilic, high MW drugs

How well did you know this?

Not at all

Perfectly

which structure is usually the site of drug action? for which of the 2 pathways does the drug usually get there?

aqueous humor corneal route conjunctiva-sclera usually goes to systemic circulation and does not get to the aqueous humor

when a drug is administered via eye drop, explain the distribution between the corneal penetration and the conjunctiva-scleral route

less than 5% of the dose goes through ocular absorption (corneal) LOSSES ARE SIGNIFICANT 50-100% gets systemically absorbed through the conjunctiva-scleral route

*true or false the non-corneal route of absorption is usually NOT productive, due to removal by the blood circulation

TRUE

true or false it is an ABSOLUTE REQUIREMENT for ophthalmic solutions to have sterility and clarity

TRUE

*4 different kinds of inactive ingredients that are added to ophthalmic solutions

preservatives (if multi dose) antioxidants wetting agents viscosity agents

*anything with "sulfite" what kind of inactive ingredient is it

antioxidant

*what is chlorobutanol

preservative

*what are polysorbate 80 and polysorbate 20 and why are they added to ophthalmic solutions?

wetting agents added to decrease interfacial tension between the eyes and the product

*"polyinyl"

viscosity agent PVA

* cellulose derivatives

viscosity agents - stay longer on the eyes

pH range for ophtalmic solutions

6.5-8.5

**what size filter is used to sterilize eye drops

0.22 micrometers

eye drops are relatively easy to prepare, filter, and sterilize what is the major problem with eye drops? what can be done to help solve this issue?

short retention time on the eye - they're very runny can add polyvinyl polymers and cellulose derivatives, or just close the eyes after applying the drops --- this will prolong contact time and LIMIT systemic exposure

poorly water soluble drugs for ophthalmic drug delivery are formulated as....

suspension

true or false ophthalmic suspensions have a longer duration of action than solutions

TRUE bc particles retained in the conjunctiva however -- large particle size also means more irritation -- so may be removed faster (LIMIT TO 10 MICROMETERS****)

why are ophthalmic ointments not very popular

greasiness and blurred vision

ophthalmic ointments are recommended to be administered at what time?

nighttime

***rank drug residence time of eye products suspensions ointments solutions

shortest - solution suspension longest - ointment

name a drug that is more effective as an eye ointment rather than solutions

antibiotics like tetracycline

true or false gels have a longer residence time than solutions

true

ophthalmic gels are formulated as in situ gels what does this mean

liquid in their container, but in contact with hotter temp or to neutral-alkaline pH, they well become gels

example of a temp-sensitive eye gel and a pH-sensitive eye gel

temp sensitive - Pluronic F-127 pH-sensitive - Carbopol 940

explain what eye inserts are

very slow drug release and long residence time to minimize systemic absorption and side effects either placed on the cornea or the lacrimal cul de sac

if patient has more than 1 drug to put in via eye drop, how long should they wait between each?

5 mins (remember - residence time is 3-5 mins) dont want to wash out the first

how can a patient limit the amount of eye drop that goes into systemic circulation? (via conjunctiva-scleral route)

pressing on the tear duct while putting in the drop and for a few minutes aftter

*in general, around ____% of ophthalmic formulations can be absorbed into the ocular tissues

less than 5%

do drugs delivered via nasal drug delivery need to be sterile

**absorption properties through the nasal cavity (ie - fast or no?)

rapid absorption and fast onset this is bc the nasal epithelium has rick vascularization

*true or false an advantage of nasal preparations is that they avoid first pass metabolism, and are also able to be self administered

true

**a disadvantage of nasal delivery is that they are limited to what kind of drug?

only potent drugs 25-200 microliters ONLY is allowed also, MW cutoff is 1000 kDaltons -- because larger than that wont be absorbed

**relative drug residence time for nasal preparations and WHY

SHORT because of the mucociliary clearance of drugs -- thus need FREQUENT administration

**true or false a disadvantage of nasal preparations is that they need to be administered frequently

TRUE - bc of short residence time due to mucociliary clearance

*true or false a disadvantage of nasal preparations is that adverse reactions are common

TRUE -- bc the cilia are very fragile

*a disadvantage of nasal delivery is that pathophysiologic conditions affect the drug permeation/absorption through the nasal mucosa why?

ie - past drug use (cocaine) may increase absorption also bloody nose and nasal congestion may affect

**enzymatic activity of the nasal mucosa and is this an advantage or diadvantage

LOWER than the GI tract - advantage (but still does have oxidative enzymes)

***major structure for absorption for nasal delivery

turbinate! has a large surface area and good blood supply

**what structure allows for drug delivery to the BRAIN through the nasal route

the olfactory region

can we deliver proteins and peptides through nasal route?

YES - less enzymatic activity than GI tract

explain what the mucociliary clearance is

body's defense mechanism - the reason that the residence time for nasal delivery is so short cilia beat at 1000 strokes/min to propel the mucus toward the nasopharynx

**true or false when formulating a nasal drug delivery, the medication must be POTENT AND be greater than 1000 daltons

FALSE potent and LESS THAN 1000 daltons

**when formulating nasal drugs, what should the hydro/lipophilicty be

balanced bc lipophilicity gives permeability and hydrophilicity allows drug to be carried in the mucus (mainly contains water)

***when formulating nasal drugs, should they be: hypertonic isotonic hypotonic

isotonic OR hypotonic -- bc hypotonic means that there is more water in the product that the nasal environment, so water will rush out of drug and the drug will thus become viscous and stay in the nasal cavity longer

***optimal size of aerosol droplets for nasal delivery

5-7 micrometers

**if aerosol droplets for nasal formulations are smaller than ____, they will be ____

smaller than 0.5 micrometers, they will be exhaled

___ and ___ are not commonly used as nasal formulations bc of irritation

ointments and powders

*to improve nasal formulations, do we want to increase or decrease the viscosity (and how do we do this)

INCREASE can add PEG or glycerin

**true or false muco-adhesives should not be included in nasal formulations

FALSE - they should be added to decrease the MCC and prolong residence time *****HOWEVER -- issue because can increase the risk of microbial contamination -- USE PRESERVATIVE!! LIKE BENZALKONIUM CHLORIDE

**name 4 things that can be added as mucoadhesives in nasal formulations to improve residence time

alginates xanthan gum HPC chitosan

*to enhance absorption of nasal formulations, ____ may be added however, what is an issue with this

surfactants however, may disrupt the nasal epithelium and cause nasal irritation

*incorporating ___ into nasal formulations can increase the drug solubility in nasal fluids

cosolvents

*what is benzalkonium chloride

preservative

*what is potassium sorbate

an antioxidant

*what is alcohol

a cosolvent

*what is polysorbate

a surfactant - enhances absorption

*what is propylene glycol

a cosolvent

*what is CMC

a mucoadhesive -- increases viscosity

*issue with mucoadhesives like gums and cellulose

increase the chance of microbial contamination --- use preservative

simplest and most convenient nasal formulation

nasal drops

issue with nasal drops

cant deliver exact amount of drug

for nasal sprays, what is the ideal ranfe of particles or droplets in order to be deposited in the nasal passages

5-7 micrometers

**patient counseling on nasal spray for migraine

keep head UPRIGHT and close mouth do NOT tilt head and do NOT lay down while delivering the dose

*true or false rapid drug absorption is expected for nasal delivery because of the RICH VASCULARIZATION IN THE TURBINATE

TRUE

*true or false nasal delivery does not avoid first pass effects

false - it does

*MW cutoff for drug absorption via nasal route

1 thousand daltons

*true or false nasal mucosa has higher enzymatic activity than the GI tract

FALSE - lower

**true or false via nasal delivery, pathophysiological condition changes account for low reproducibility of absorption and action

TRUE ie - mucus, blood, destroyed area, not inhaling completely, etc issue with nasal delivery is LOW REPRODUCIBILITY

can intranasal deliver drugs to the brain

yes - through the olfactory region

Ophthalmic and Nasal part 1 (7 concept 2 calcs) Flashcards

(92 cards)