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1. Eye drops
Overflow on eyelids
!. Eye ointments
. Ophthalmic gels
Matted eyelids
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Tear evaporation
÷rug metabolism
Nonproductive absorption
adjustment of tonicity,
increasing solubility,
imparting viscosity,
solvent
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Objective of ocular N÷÷S is to maintain the drug in the biophase for an
extended period of time.
The anatomy, physiology & biochemistry of the eye render this organ
impervious to foreign substances.
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÷rug solution drainage is the most significant factor in reducing the
contact time of the drug with the cornea & consequently ocular
bioavailability of topical dosage forms.
The ophthalmic dropper delivers 50-75 µm of the eye drops. Ôf the patient
does not blink, the eye can hold about 30 µm without spilling on the cheek.
The natural tendency of the cul-de-sac to reduce its volume to 7-10 µm.
The conjunctiva also possess relatively large surface area making the loss
significant.
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Both conjunctival & nasal mucosa are the potential sites for systemic
absorption of topically applied drug.
Tears dilute the drug remained in the cul-de-sac which reduces the
transcorneal flux of the drug. The drug entity, pH, tonicity of the dosage
form as well as formulation adjuvant stimulate tear production.
Metabolism in the precorneal area also account for the further loss of the
drug.
÷ue to all these factors typically less than 1% of the instilled drug
reaches aqueous humor.
Ô. Use of polymers
ÔÔ. Mucoadhesives
Ô . The NODS
Ô. Nanoparticles
ÔÔ.Liposomes
ÔÔÔ.Prodrugs
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Ôncorporation of polymers into an aqueous vehicles increases the ocular
contact time of drug.
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Ôn considering this approach of increasing solution viscosity to enhance
ocular drug absorption the lipophilicity of the drug should be taken into
account.
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External surfaces of the globe of the eye is coated with the thin film of
glycoprotein called as mucin.
Goblet cells on the conjunctiva secrets mucin & it forms the thin layer
over conjunctiva & cornea.
The mucin layer is capable of taking about 40-80 times its weight of
water due to substantial number of sugar groups present in polypeptide
backbone.
The mucin layer forms a part of precorneal tear film which continuously
bathes the corneal epithelium, conjunctiva epithelium & cul-de-sac.
Natural & synthetic polymers that bind to the mucin non covalently used
for drug delivery.
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These bioadhesive polymers help in prolonging the release of the drug
from a dosage form by localizing it at a specific site where mucus present.
They remain in contact with the precorneal tissues until mucin turnover
causes elimination of the polymer.
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Polymer based delivery devices for placement into cul-de-sac.
Ôt offers an attractive approach to the problem of prolonging precorneal drug residence time.
Ôt also offers the potential advantage of improving patient by reducing the dosing frequency
1. Comfort
2. mack of explosion
6. Sterility
7. Stability
8. Ease of manufacture
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Ophthalmic inserts are of 2 types:
1. Nonerodible Inserts
i. Ocusert
iii. Ocufit
2. Erodible Inserts
i. The macrisert
ii. SO÷Ô
iii. Minidisc
Smaller devices are better retained than larger ones & rod shaped are better
retained than oval ones.
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Physician acceptance;
User acceptance;
Ease of handling and insertion;
Patient comfort;
mack of expulsion during wear;
mack of toxicity;
Non-interference with vision and oxygen permeability
Reproducibility of release kinetics;
Applicability to a variety of drugs;
Sterility;
Stability;
Ease of manufacture;
Reasonable price;
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Reduction of systemic absorption (which occurs freely with eye drops via
the nasolacrimal duct and nasal mucosa);
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1. Thickness of film
2. Content uniformity
3. Uniformity of Weight
9. Compatibility study
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Ôt is developed by Alza Corporation
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All these four membranes put together
Retaining ring of EVA(Ethylene Vinyl Acetate) impregnated with Ti02 for visibility
purpose
The higher release rate of Ocusert® Pilo 40 is achieved by making its rate
controlling membrane thinner & by the use of flux enhancer di 2-
ethylhexyl)phthalate
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Therapeutic soft lenses are often used to aid corneal wound in patients
with infection, corneal ulcers, characterized by marked thinning of cornea.
Most of the drug released in first 30 minutes from presoaked contact lens.
The supply of oxygen to the eye tissues & the build up of harmful
metabolite such as CO2 complications also arises during use of presoaked
contact lens.
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Thus, an alternative approach is to incorporate the drug either as solution
or suspension of solid particles in the monomer matrix.
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Ôt is a sustained release, rod-shaped device made of silicone
elastomer
conjunctival fornix
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The insoluble OcufitX reportedly combines two
important features, long retention and sustained
drug release. When placed in the upper fornix of
volunteers, placebo devices were retained for 2
weeks or more in 70% of the cases
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Ôt is inserted into the inferior fornix where it imbibes
the water from the conjunctiva & cornea, forms a
hydrophilic film which stabilizes the tear film &
hydrates, lubricates cornea.
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Soluble Ophthalmic ÷rug Ônsert (SO÷Ô) is a small oval wafer developed by
Soviet scientists
The film turns into a viscous polymer mass, thereafter in 30-60 minutes it
becomes polymer solution
A single SO÷Ô application constitutes once a day therapy for the treatment of
glaucoma
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Ôt consists of a contoured disc with a convex front & a concave back
surface in the contact with the eye ball.
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The new ophthalmic delivery system (NO÷S) is a method of
presenting drugs to the eye within a water soluble drug loaded film
On contact with the tear film in the lower conjunctival sac the
membrane quickly dissolves releasing the flag into the tear film
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Collagen:
Collagen is a naturally occurring protein that is totally safe for use on and
in the body
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Potential use for the collagen shields is that of ocular surface protection
Ôn nearly all types of eye surgery, the surface coat (the sclera or the
cornea) must be incised to allow access to the interior part of the eye
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These bandage contact lenses are expensive and have been associated with
some complications, particularly when they are used over a long period of
time
Preliminary results have shown that the collagen shield can indeed provide
an adequate protective environment to allow healing of surgical and
traumatic wounds to the eye
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Size,
Charge of liposomes,
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Ôt is considered that solid particles intended for ophthalmic use should not
exceed 5²10 micron diameter
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miposomes a potentially useful system for ocular delivery they are not very
popular because of their short shelf life, limited drug capacity, and
problems in sterilization
Use of either the viscosity increasing agent with vesicles and/or the use of
penetration enhancers along with the vesicles in the formulation. Viscosity
imparting agents prolongs the corneal contact time whereas penetration
enhancers increase the rate and amount of drug transport
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Prodrugs are pharmacologically inactive derivatives of drug molecules that
require a chemical or enzymatic transformation in order to release the
active drug within the body
Prodrugs are simple chemical derivatives which are one or two chemical or
enzymatic steps away from the parent drug
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Drugs Prodrugs Therapeutic use
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Several monoesters also prolonged the duration of action 1.5 times compared
to pilocarpine. The poor aqueous stability of the monoesters limited their
practical use
The half-lives of monoesters in aqueous solution (pH 7.4) varied from 0.5 h to
18 h at 37°C. Although monoesters are more stable in acidic solutions, the
preparation of ready-to-use eye drops with an acceptable shelf-life was not
possible
The stability problem of pilocarpic acid monoesters was overcome by using the
double prodrug concept
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This is an alternative approach to improve the bioavailability of ocular drugs by
incorporation of penetration enhancers
Another approach is ion pair formation which results in altered drug species with
respect to ionic size, diffusivity & partitioning behavior
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Ô. Use of polymers
Ocular iontophoresis
ÔÔ. Mucoadhesives
Ôntraocular solutions
ÔÔÔ. Ophthalmic Ônserts
Ô . The NODS
Ô. Nanoparticles
ÔÔ.Liposomes
ÔÔÔ.Prodrugs
Ôt is a non-invasive technique
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Ôontophoresis usually employs low voltage (10 V or less) to supply a
continuous direct current of 0.5 mA/cm2 or less.
Thus, positive ions (cations) are attracted to the negative electrode (or
cathode) and repelled by the positive electrode (or anode).
Conversely, negative ions (anions) are attracted to the positive electrode and
repelled by the negative electrode.
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The drug is applied with an electrode carrying the same charge of the drug,
& the ground electrode, which is of opposite charge, is placed elsewhere on
the body to complete circuit.
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These basic operational guidelines have enabled
iontophoresis to be used to enhance drug delivery in a
wide variety of conditions.
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V = ÔR
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Q = ÔT
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F is Faraday·s constant
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Faraday·s constant is the electrical charge carried by 1
gram equivalent of a substance.
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This non-invasive drug delivery system minimizes the risk of trauma due
to drug delivery ways such as intravitreal or peribulbar injections, possible
risk of infection and inflammation and hemorrhages.
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A metal electrode that is connected to a direct current
power supply is submerged in the solution in the eyecup
without making contact with the surface of the eye.
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With the hand-held applicator probe, the metal (platinum) electrode
extends into the eyecup that is filled with the drug solution.
Ôn general, the current should not exceed 2.0 mA and the time be no
longer than 10 min.
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Therefore, the platinum electrode connected to the anode (the
positively charged pole) is placed in contact with the solution.
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Glaucoma
Ocular Anesthesia
Ocular Ônflammation
Ocular Ônfection
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Company Model
ÔOME÷, Ônc Phoresor ÔÔ Auto- PM900
Give different advantages of ocular drug delivery systems over conventional ophthalmic
formulations. (2)
Explain in detail with examples the role of polymers in ocular drug delivery systems.(2)
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