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Drew 924 > Ophthalmic Delivery > Flashcards

Ophthalmic Delivery Flashcards

1
Q

What are the disadvantages for ophthalmic delivery?

A

1) sterility
2) poor retention
3) local ADRs

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2
Q

What are the desired characteristics of an ophthalmic product?

A

1) good penetration
2) easy admin
3) few ADRs

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3
Q

How are tears drained?

A

zipper like motion to superior & inferior punctum –> lacrimal duct

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4
Q

What is the normal rate of tear production?

A

1 - 25 uL/min

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5
Q

What is the normal tear volume?

A

10 - 20 uL

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6
Q

What is the pH range & mean in the eye?

A

5.2 - 8.3 (7.4)

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7
Q

What molecules provide buffering in the eye?

A

bicarb & proteins

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8
Q

What is the protein concentration in tears?

A

5.4 mcg/mL

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9
Q

What proteins are present in tears?

A

1) primarly lysozyme
2) dehydrogenases
3) amylase
4) esterase
5) albumin
6) immunoglobulins

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10
Q

What is the osmotic concentration in a tear?

A

310 - 350 mOsm

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11
Q

When is pH decreased?

A

1) awakening

2) secretions

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12
Q

How is dry eye measured?

A

Schirmer test

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13
Q

What drug properties induce tearing?

A

1) pH away from 7.4
- -alkali is worse
2) osmotic concentration not 310
- - hyper is worse
3) large particle size

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14
Q

How does conjunctival surface area relate to that of the cornea?

A

17x more area in conjunctiva

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15
Q

What conjunctival factors stimulate tearing?

A

pressure receptors

– dust, rubbing

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16
Q

What is the main barrier for drug delivery to the anterior chamber?

A

the cornea

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17
Q

Describe the hydrophobicity/hydrophilicity of the epithelium.

A

HYDROPHOBIC

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18
Q

Describe the hydrophobicity/hydrophilicity of the stroma.

A

HYDROPHILIC

– 70 % water

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19
Q

Describe the hydrophobicity/hydrophilicity of the endothelium.

A

thin & HYDROPHOBIC

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20
Q

What is the rate-limiting barrier for log K < 1

A

epithelium

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21
Q

What is the rate-limiting barrier for log K = 1-2.5?

A

endothelium

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22
Q

What is the rate-limiting barrier for log K > 2.5?

A

stroma

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23
Q

When would faster membrane transport be expected?

A

inflammation of that membrane

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24
Q

Which corneal layer contains efflux pumps?

A

endothelium

25
Q

What are Lipinski’s ORAL rules of 5?

A

1) MW > 500 Da
2) H donors > 5
3) H acceptors > 10
4) log K > 5

26
Q

What are Lipinski’s CORNEAL rules of 5?

A

1) MW > 500 Da
2) H donors > 3
3) H acceptors > 8
4) log K > 4.2

27
Q

Describe the log K of epinephrine.

A

low! hydrophilic

28
Q

How is epinephrine’s permeability increased for ophthalmic delivery?

A

ester increases permeability

– esterase converts prodrug

29
Q

What are the post-corneal factors for drug delivery to the eye?

A

1) metabolism

2) iris adsorption

30
Q

How is viscosity increased for delivery?

A

1) ointments
2) polymer inclusion
3) self-gelling systems

31
Q

What polymers are used to increase viscosity?

A

1) PVA

2) methylcellulose

32
Q

What substances are used in self-gelling systems?

A

1) tromethamine

2) gellan gum

33
Q

What molecules do self-gelling systems depend on in the eye?

A

divalent cations in the tear film

34
Q

How is residence time increased (other than viscosity alteration)?

A

1) non-erodible techniques
- - Ocusert or implant
2) erodible techniques
- - implant
3) sterile dressing

35
Q

Describe the components of ocusert.

A

1) reservoir
2) ethylene acetate RCM
3) visibility ring

36
Q

Describe the application of ocusert.

A

Inserted 1 x/wk

37
Q

Describe 2 erodible products used to increase residence time.

A

1) Lacrisert (lower eyelid implant)

2) Ozurdex (intravitreal implant)

38
Q

What is Lacrisert for?

A

dry eye

39
Q

What is the polymer in Lacrisert?

A

HPMC

40
Q

How is Ozurdex implanted?

A

surgically (intravitreal)

41
Q

Describe the structure of collagen.

A

alpha-helix of 3 polypeptide chains

    • 1/3 glycine, 1/4 proline
    • hydrophilic
42
Q

How is a collagen dressing drug released?

A

protease

43
Q

How is degradation decreased for a sterile collagen dressing?

A

increased cross-linking

44
Q

How can drug loss be minimized (drug delivery form)?

A

1) NODS

2) application device for elderly

45
Q

What is NODS

A

medicated tab w/ flag when film dissolves in tears

– fast dissolution requires amorphous drug forms

46
Q

What are preservative agents?

A

1) Benzalkonium chloride 0.01%
2) Chlorbutanol 0.5%
3) Phenylmecuric nitrate 0.004%
4) Methylparaben 0.1 - 0.2%

47
Q

What are antioxidant agents?

A

1) EDTA 0.1%
2) Sodium bisulfite 0.1%
3) Sodium metabisulfite 0.1%

48
Q

What is the cause of age-related macular degneration?

A

leaky blood vessel in the posterior chamber

49
Q

What are Sx of macular degeneration?

A

1) blurred/distorted objects
2) straight lines appear wavy
3) poor low-contrast & glare vision

50
Q

How is age-related macular degeneration treated?

A

Intravitreal injection

51
Q

How is intravitreal injection administered?

A

< 1 mL via 27-30 gauge needle

52
Q

What is the treatment prior to intravitreal injection?

A

1) povodine-iodine on the eyelids

2) lidocaine

53
Q

What is Fick’s Law?

A

Flux = DAK/h * ∆C

54
Q

What is Retisert?

A

erodible surgical implant for chronic posterior uveitis

delivers chronic steroid over 6 months

55
Q

What is the polymer in Retisert?

A

PLGA (polyacticglycolic acid)

56
Q

What is Ozurdex?

A

Dexamethasone in PLGA pellet

57
Q

Why is Ganciclovir for AIDS-related CMV retinitis supplied in an implant?

A

Ganciclovir has

    • poor bioavailability
    • poor Lipinski prediction
58
Q

Ganciclovir implant… erodible or not?

A

non-erodible

Drew 924 (16 decks)

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