Studi biofarmasi obat yang

diberikan melalui mata

Mirnawati salampe

Eye is considered as the

window of our soul

Topical administration for ocular

therapeutics is ideal because of
smaller doses required compared to
the systemic use, its rapid onset of
action and freedom from systemic
toxicity
Topically applied ocular drugs have
to reach the inner parts of the eye
and transcorneal penetration is
believed to be the major route for
drug absorption.
Corneal absorption is much slower

Eye is most interesting organ due to its

drug disposition characteristics
Conventional ophthalmic formulations like
solution, suspension, and ointment have many
disadvantages which result into poor
bioavailability of drug in the ocular cavity

The first one is based on the use of

sustained drug delivery systems, which
provide the controlled and continuous
delivery of ophthalmic drugs.
The second involves maximizing corneal
drug absorption and minimizing precorneal

There are two barriers namely, static

and dynamic barriers that limit the
ocular drug delivery.
Static barrier is composed of
different segments of eye such as
cornea, sclera, retina and bloodretinal barriers
whereas dynamic barriers consists
of choroidal and conjunctival blood
flow, lymphatic clearance, and tear

About 5% of dose instilled into

the eyes reaches the intraocular
tissues due to various factors
like pre-corneal drainage and
less permeability of corneal
epithelium cells

ANATOMI MATA

ROUTES OF OCULAR DRUG DELIVERY

Topical route
Subconjunctival
administration
Intravitreal
administration

BARRIERS FOR OCULAR DELIVERY:

Drug loss from the ocular surface

Lacrimal fluid-eye barriers/corneal
ephitelium barrier
Blood-ocular barriers
blood-aqueous barrier and blood-retina
barrier (RPE)

OCULAR DRUG ABSORPTION

MECHANISM OF OCULAR DRUG

ABSORPTION
Corneal permeation
transcorneal drug permeation,
the cornea can be considered to consist of
three primary layers (epithelium, stroma
and endothelium).
Non-corneal permeation
These non-corneal routes involve drug
diffusion across the conjunctiva and sclera
and appear to be particularly important for
drugs that are poorly absorbed across the
cornea

Permeasi melalui kornea

Kornea
Organ

transparan, avaskular,
tebal 0,5-0,7 mm, diameter 11,5
mm
3 lapisan (epitelium, stroma,
endotelium)
Epitelium (lipofilik/ tight junction)
Stroma (hidrofilik)
Endotelium (lipofilik)

MEKANISME
PERMEASI

TRANSELULER

PARASELULER

CARRIER
MEDIATED
TRANSPORT

PORI/INTERSELLUL
ER

Factors Affecting the Bioavailability of Topically Drugs

Pre-corneal fluid drainage

Drug binding to tear protein

Systemic drug absorption

Corneal Factors

Melanin binding:
Drugs metabolism

Factors Affecting the Bioavailability of

Topically Drugs
1.
2.

3.
4.

Volume air mata normalnya 7l

Air mata mengandung 0,7 % protein
(penurunan respon miotic pilokarpin
dengan adanya albumin precorneal)
Air mata mengandung enzym
lyzosim yang mendegradasi obat
Obat terikat pada melanin yang ada
di iris, badan siliaris, RPE, choroid

Faktor yang mempengaruhi permeasi obat

melalui kornea

Fisiologi
Fisikokimia
Formulasi

Faktor fisiologi
Precorneal

Pergantian air mata (normal 7L)

Aliran larutan

Epinefrin, dosis
berkurang 90%
(2
detik 50L, 4 detik 25
L, 6 detik
10 L)

Ikatan protein

Absorpsi non produktif (melalui

konjunktiva)

Faktor Membran

Epitelium ( koefisien partisi obat >1:

high penetration)

Endotelium (koefisien partisi 0,6-1: high

penetration

Stroma (hidrofilik)

Faktor fisikokimia
Koefisien
partisi

Hidrofilik
koefisien
partisi <0
resisten
melintasi
epitelium
kornea

Derajat ionisasi

Mempengaru
hi difusi
melewati
membran
Union
(peningkatan
penetrasi)

Ukuran molekul

>500 Da, sulit

melintasi membran

Faktor formulasi
konsentra
si

Peningkatan
konsentrasi
menyebabka
n hipertonik
(peningkatan
lakrimasi)
1% pilokarpin
bioavailabilita
sx 2x lebih
besar dr pada
4% dan 2,5x
pada 8%)

Laju disolusi,
ukuran partikel

Peningkatan
ukuran
partikel
mempengar
uhi
bioavailabilit
as
(penurunan
laju disolusi
dan
eliminasi di
cul de sac)

pH, tonisitas

pH (7,14-7,28)

280-293 mosm/kg
(sleep)

302-318mosm/kg
(open)

Hipotonik
meningkatkan
permeabilitas
epitel kornea)

pH 4,5-7 tidak
mempengaruhi
permeabilitas

pH alkali
meningkatkan
lakrimasi

viskositas

perpanjan
g waktu
kontak

PVA, PVP,
METIL
SELLULOS
A

1-15 cps

12-15 cps

Strategi yang dikembangkan

Sistem

pembawa (siklodextrin) untuk meningkatkan penetrasi transkorneal

In situ activated gel forming Systems untuk meningkatkan waktu kontak
dengan kornea
( Poloxamer 407 (a polyoxyethylene polyoxypropylene block copolymer) is
a polymer with a solution viscosity that increases when its temperature is
raised to the eye temperature.
Cellulose acetophthalate (CAP) is a polymer undergoing coagulation when
the original pH of the solution (4.5) is raised to 7.4 by the tear fluid.
Mucoadhesive polymer yang berikatan dengan mucin konjungtiva
(hydroxypropylcellulose, polyacrylic acid, high-molecular-weight (>200,000)
polyethylene glycols, dextrans, hyaluronic acid, polygalacturonic acid,
xyloglucan, etc.)
sodium alginate, forms a gel in the cul-de-sac due to the presence of
divalent calcium ions in the lacrimal fluid

SISTEM BARU DALAM PENGOBATAN

OCUSERT
LENSA HIDROGEL
YANG LIPOFILIK
ITS (IMPLAN
THERAPEUTICS
SOLUBLE)