OPHTHALMICS, EAR, AND NASAL PREPARATIONS

Question 1

What are Ophtalmics?

Answer 1

Sterile products for instillation into the eye
-can be solutions, suspensions, ointments, emulsions, gels
and ophthalmic inserts
-we want an local effect not systemic

Question 2

When are Ophtamlics used?

Answer 2

used include anti-inflammatories, antibiotics, vasoconstrictors, miotics (Glaucoma), anesthetics, antifungals, antivirals, mydriatics (relax the pupil before eye testing), and cycloplegics (to relax ciliary muscle)

Question 3

Pros and Cons:

Answer 3

Pros:
▪ Convenient
▪ Noninvasive
▪ Self-administration
▪ Reduced systemic side effects

Cons:
▪ Low bioavailability
▪ Inability to reach a posterior segment of the eye
▪ Low drug retention and frequent administration bc of the low volume administered

Question 4

The human eye:

Answer 4

The cornea, lens, & vitreous body don’t have blood vessels
-> Oxygen and nutrients are transported to nonvascular areas by aqueous humor

Question 5

Tear volumes:

Answer 5

-Normal tear volume: 7-8 μL
-non-blinked state: 30 μL
-blinked state: 10 μL
-quantities must be small with high concentration, Drops vary in size but approx. 50 μL

Question 6

How can Opthalmics be sterilized?

Answer 6

Most common: Autoclave (terminal after preparing)
if not possible -> Filtration
-Dry Heat, Gamma Radiation, Ethylene Oxide

-Sterility Test has to be performed: Direct inoculation and membrane filtration

Question 7

When and which preservatives are used?

Answer 7

When single-dosed, not needed; avoid after surgery

-Multiple-dose: preservatives can be irritating, so only use those:
Benzalkonium chloride (BAK), Benzethonium chloride, Chlorobutanol, Phenylmercuric acetate or nitrate, Thimerosal

-make sure it is effective against certain bacteria like Pseudomonas

Question 8

What are the ideal pH and Viscosity range for Opthamlics?

Answer 8

-protect against pH change
-Ideally: 7.4, basic is more preferred than acidic (irritating)

-Optimum viscosity: 15-25 cp obtained by adding Viscositx agents:
MC: Methylcellulose, HPMC: Hydroxypropyl methylcellulose, HEC: Hydroxyethylcellulose
Gelling agent -> PVP: Polyvinylpyrrolidone, PVA: Polyvinyl alcohol

Question 9

What are the antioxidants and how to obtain ISOTONICITY for Opthamlics?

Answer 9

Antioxidants to prevent oxidation
-EDTA chelating agents, Sodium bisulfite, Thiourea

Isotonicity: 0.6-2.0 % NaCl or its osmotic equivalent

Question 10

What are different ophthalmic drugs?

Answer 10

-Solutions: most common
-Suspensions: Fine particle size <10 µm - Shake before use
-Emulsion: Shake before use
-Ointments: More viscous allowing the drug to stay longer in the eye -> melt at room temperature and release the drug
-Inserts: Gel-polymer with multiple layers for extended-release f.e. Pilocarpine for Glaucoma 20-40 µg/h in 7 days
-Contact lens: Corrective, Cosmetic, or therapeutic

Question 11

How are ophthalmics packaged?

Answer 11

Glass or Plastic: 2 to 30 mL, sometimes with a small syringe

Question 12

What is the BUD for compounded Ophthalmics?

Answer 12

Nonpreserved aqueous: 14 days
Preserved aqueous: 35 days

Question 13

What are the requirements for Ophthalmic Ointments?

Answer 13

-extended residence time on the eye
-must not be irritating to the eye
-must melt at room temperature, for comfort and drug release
-USP sterility test and metal particle test

Question 14

What is the correct method of Ointment Application?

Answer 14

1. Wash hands
2. tube should not touch eyelid
3. head should be tilted back, eyelid should be gently pulled
   downward
4. insert a thin ribbon into eye sack

Question 15

Advice for patients:

Answer 15

-blurred vision, better at bedtime
-If multiple medications are to be given wait 5-10 min so that one doesn’t dilute the other one
-eye drops first before the ointment
-NEVER eardrops for eyes

Question 16

Contact Lenses:

Answer 16

-Soft lenses use a hydrogel such as a hydroxyethyl methacrylate (HEMA), hard ones out of plastics

-silicone hydrogels for extended wear due to high oxygen
permeability

-Multipurpose Solutions for Rinsing AND Enzymatic cleaning, Disinfection & Neutralization for cleaning

Question 17

How is the backside of the eye treated?

Answer 17

-Intravitreal injections
-Iontophoresis (still research) - charged drugs with electrical current to push it to the back of the eye

Question 18

What are Otic or Aural preparations?

Answer 18

For delivery of drugs into the ear canal for localized action

Barriers: Tympanic membrane, middle ear

Question 19

What are the indications and dosage forms?

Answer 19

Dosage forms: Drops or solution; suspensions, ointments, and foams (for longer retention)

Indication: removal of excessive cerumen (earwax), ear infection, pain

Question 20

Why may there be sterile and nonsterile ear meds?

Answer 20

-If there is a chance of entrance into the inner ear, due to eardrum rupture or after surgery sterile products should be used

Question 21

Which drug is used to remove Cerumen from the ear?

Answer 21

The most often used OTC drug for earwax removal is Debrox

-earwax is a lipid so for removal, a surfactant is needed
-Carbamide peroxide (6.5%) dissolved in glycerin and propylene glycol (increasing the viscosity so that it stays longer in the ear)
-carbamide peroxide releases oxygen which disrupts the wax -> easy removal

Question 22

Which vehicles are used in the formulation of ear drops?

Answer 22

To increase viscosity and the retention in the ear
▪ Propylene glycol
▪ Polyethylene glycol (Low MW)
▪ Glycerin
▪ Mineral oil
▪ Olive oil

Question 23

When formulating an otic suspension, which property should be paid attention to?

Answer 23

pH bc it could be irritative
ideal range is 3 to 3.5

Question 24

How should ear drops be administered?

Answer 24

-wash hands
-Shake if it is an emulsion or suspension
-warm the bottle for 3 min
-tilted position or lie down
-to children 3 or less: downwards
-4 or older: ear upward and backward

-keep on taking the drug for 3 days after the symptoms

Question 25

What are the features of the nasal cavity used for drug administration?

Answer 25

-Highly vascular mucosa (f.e. fast onset in Naloxone)
-Surface area about 180 cm2
-Total volume about 20 m

Question 26

What are the Absorption barriers of the nasal cavity?

Answer 26

▪ Physicochemical properties
▪ Enzymes in nasal fluid
▪ Mucociliary clearance of particles (that are not in certain size range)

Question 27

Why can the nasal cavity be used for CNS drug delivery?

Answer 27

Because the nose has Olfactory nerves for smelling that goes to the brain

Question 28

Indication of nasal drugs:

Answer 28

Locally: Congestion, Stuffiness, Inflammation, Pain. Allergy, infections
-> nasal steroids, lubricants, antihistamines, decongestants and anti-infectives

Systemic: Opoiod overdose, Migraine, delivery to the brain

Question 29

Nasal decongestants and Solutions:

Answer 29

Used for treatment of rhinitis
▪ Isotonic (0.9% sodium chloride) aqueous solutions with pH close to nasal fluids (pH 5.5 to 6.5)

-If local sterilization is not required, but if they are systemic they do
-Preservatives for multiple doses, for single dose not needed

Question 30

What are the factors influencing drug deposition upon delivery via nasal sprays?

Answer 30

-dose volume: 50 - 100 µL, more than 100 µL can cause post-nasal drip

-Spray pattern and plume geometry: wide angle of plume and more spray area and we don’t want it to be administered to the back of the throat
-> they are affected by the shape of the nozzle and the size of the pump

-Droplet size distribution: smaller particles are more convenient, depending on the force applied when administering

-Velocity of the droplet: faster administration with swirling devices have a longer retention

Question 31

Formulation-related factors:

we want a WIDER PLUME ANGLE AND LOW VISCOSITY!

Answer 31

Viscosity: less viscous formulations are more convenient and are associated with a wider angle of plume -> wide enough to cover the focussed area in the cavity

-Thixotropy: when administered we want the viscosity to reduce and regain the viscosity in the nasal cavity to prevent post-nasal drip

-Surface tension: the lower the surface tension, the smaller the size of droplets, the lesser the viscosity -> finer mist

Question 32

Why is Flonase Sensimist better than the common Flonase?

Answer 32

Its salt form binds better to the Glucocorticoid receptor (better affinity)
-Higher potency (lower dose)
-Patented MistPro Technology- finer mist with less viscosity
-less nasal drip due to better thixotropy property (regain of viscosity)
-The wider angle of the plume (35°C)

Question 33

How should the head be positioned when using nasal sprays?

Answer 33

-pressurized nasal canister: head backward

-Pumps: head forward

-never apply to the nose septum (highly vascularized and can cause nose bleeding) nasals steroids can cause nose drying and bleeding

Question 34

How can the nose be used to administer drugs into the lungs?

Answer 34

Inhalation -> with drug solutions administered by the nasal or oral
respiratory route
-locally in the lungs or systemic
-administered as aerosols using nebulizers (produce particles between 0.5-5 µm, bronchial asthma)

Question 35

What are Inhalants?

Answer 35

Drugs with high vapor pressure (they are volatile)
-opened when ready to use
f.e.: Amyl nitrite (vasodilator, angina), propylhexedrine
(vasoconstrictor, decongestant)

Question 36

What happens if nose sprays are used over a period of time?

Answer 36

rebound congestion
nasal drugs are vasoconstrictors of blood vessels which may also cause congestion