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TRANSDERMAL
DRUG DELIVERY SYSTEM

OLEH
Dr.TETI INDRAWATI MS.APT.
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PENDAHULUAN

ORAL MEDICATIONS

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 Faktor yang mempengaruhi
penyerapan perkutan :

 Keadaan & umur kulit

 Aliran darah
 Tempat pemberian
 Suhu dan kelembaban

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 Gambar kulit

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 SKEMA BERBAGAI DIFUSI OBET KE LPS KULIT

PELARUTAN ZAT AKTIF

DIFUSI ZA : PEMBAWA ….PERMUKAAN KULIT

LINTASAN TRANSDERMIS LAPISAN FOLIKULER

KOEF. PARTS PEMBW-LPS.TANDUK KOEF. PEMBW-SEBUM

DIFUSI MELLMATRIKS PROTIDO- DIFUSI MELL LIPIDA DLM KEL. SEBASEA

LIPIDA STRAT.KORNEUM/TANDUK

KOEF.PARTS.THP EPIDERMIS MALPIGHI

DIFUSI KE EPIDERMIS HIDUP

DIFUSI KE DERMIS

DIFUSI MELL DINDING PEMBL.DRH MSK

SIRKLS SISTEMIK

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 TRANSDERMAL
DRUG DELIVERY SYSTEM

Suatu sediaan obat yang diberikan secara

topikal untuk diabsorpsi sistemik melalui kulit
dengan laju terkendali dalam jangka waktu
yang panjang

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Umum : obat diisikan pada suatu
lapisan reservoir yang
didukung penyangga

Difusinya dikendalikan membran semipermeabel

di atas reservoir

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 FAKTOR

KEBERHASILAN

BIOLOGI FISIOLOGI
BIOKIMIA BIOFISIKA

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 KEBERHASILAN

1. Lokasi badan ...... aplikasi

2. Ketebalan, komposisi dan integritas dari lapisan kulit luar
corneum( suatu lapisan kulit)
3. Ukuran dan struktur molekul ( bobot molekular),
4. Permeabilitas membran di sistem penghantaran obat
transdermal
5. Status hidrasi kulit
6. pH dan sifat fisikokimia kekayaan obat/racun
7. Metabolisme obat
8. Kelarutan dalam lemak
9. Derajat pemisahan obat & penggabungan komponen pd kulit
10. Depot ( reservoir) obat di kulit
11. Perubahan aliran darah di kulit dengan aditip dan T badan
12. Interaksi di antara faktor di atas
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Permasalahan :
PENETRASI LAMBAT, PERMEABILITAS RENDAH

SENYAWA bm >>
TDK BS LEWAT

1. Hindari zat asing/ berbahaya masuk dari

luar.
2. Kulit harus terbuka bagi transpot obat dari
luar, untuk menerima perawatan optimal.

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 SISTEM PENYERAHAN OBAT IDEAL
( IDDS)

1. Mampu menghantarkan obat (~ ukuran atau struktur) dg

kecepatan spesifik.
2. Profil penghantaran selektif (spesifik)
3. Mampu menghantarkan lebih dari 1 obat pd a waktu
4. Flreksibel, IDDS mempunyai kemampuan untuk mengubah
atau menyesuaikan kecepatan / pemilihan waktu atau jumlah
utk dihantarkan.
5. Sensoring, Monitoring, dan Decision-Making (Sistem
penyerahan " yang cerdas" )
6. Targeting.
7. Kapasitas. Sistem mampu membuat pengulangan
penghantaran.
8. Tidak ada permasalahan
9. Handal
10. Nilai Pasar Tinggi

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Gambar kulit

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 Gambar kulit

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 Stratum lpsn.
papilary Sirkulasi
corneum
darah

absorpsi

epidermis dermis subdermal

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 lokalisasi
Obat dlm O di jaringan Respon
sediaan target

topikal
release

absorpsi
distribusi
O.dlm cairan

transderma
sekresi kulit

O dlm sirkulasi drh eliminasi

Stratum
sistemik
corneum

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 Kompartemen
epidermis
cuplikan

Lubang
kulit
pengembilan
Sambungan cuplikan
teflon

sekrup
Kompartemen
cairan dermis

Bola kaca

SEL DIFUSITANPA PENGGANTIAN

DDS
KOMPARTEMEN DERMIS
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 SEL DIFUSI PENGGANTIAN KOMPARTEMEN DERMIS &
PEREDARAN DLM KOMPARTEMEN EPIDERMIS

SAMBUNGAN

KOMPARTEMEN
EPIDERMIS

KOMPARTEMEN
SEL DIFUSI TANPA DERMIS
PENGGANTIAN
KOMPARTEMEN KULIT

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 PERKEMBANGAN SISTEM TERAPI
TRANSDERMAL

1. SISTEM MEMBRAN MODERAT

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 6 komponen dlm The Androderm systems (gbr 1) ;
1. Metallized polyester/SurlynÒ* (ethylene-methacrylic acid
copolymer)/ethylene vinyl acetate backing film with alcohol
resistant ink,
2. a drug reservoir of testosterone USP, alcohol USP, glycerin USP,
glycerol monooleate, methyl laurate, sodium hydroxide NF, to
adjust pH, and purified water USP, gelled with carbomer
copolymer Type B NF,
3. a permeable polyethylene microporous membrane,
4. a peripheral layer of acrylic adhesive surrounding the central,
active drug delivery area of the system. Prior to opening of the
system and application to the skin, the central delivery surface
of the system is sealed with a peelable laminate disc
5. composed of a five-layer laminate containing
polyester/polyesterurethane adhesive/aluminum foil/polyester-
urethane adhesive/polyethylene. The disc is attached to and
removed with the release liner (
6. a silicone-coated polyester film, which is removed before the
system can be used.
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 2. SISTEM ADHESIF DIFUSI TERKONTROL
Lapisan adhesiv
Reservoir o
Pengontrol kecepatan
3. DDS TRANSDERMAL DG DIFUSI TERKONTROL Reservoir o
Pengontrol
kecepatan
Lapisan adhesiv

3. DDS TRANSDERMAL DR MATRIKS DISPERSI

ADSORBEN
OCCLUSIVE BASEPLATE
IMPERPEABLE BACKING
Al foil
POLIETILEN
Adhesive
rim

4. S. MIKRORESERVOIR (KOMBINASI RESERVOIR & DIS. MATRIKS)

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Transdermal drug delivery:

1. Iontophoresis
A non-invasive method of delivering the drug molecules by using a
small electric current to enable charged drugs to permeate through the
skin. The delivery of electric current to the skin alters its permeability
that enables the increased migration of the drug into the epidermis.
The factors that influence iontophoresis :
1. pH kulit
2. drug dosage,
3. physical and chemical properties of the drug molecule,
4. current, voltage and resistance.

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2. Electric patch and micro needle
Electric patch based transdermal delivery was developed by ALZA
Corporation through its E-TRANS electro transport technology.
This offers higher flexibility than iontophoresis by being able to
deliver a wider range of drug molecules depending on required
dosage. ALZA’s Macroflux technology uses a thin titanium screen
that consists of 200µm projections that create pathways to deliver
the drug through the stratum corneum. Coupled with the
Macroflux® transdermal technology, further enhancement of rate
of drug delivery can be achieved.

vaccines, small molecules and

larger complex biopharmaceuticals.

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 Figure 2. The layers that comprise the matrix (drug-in-
adhesive) type of patch. The protective liner is
removed prior to applying the patch to skin.

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3. Sonophoresis

Penggunaan energi ultrasoun level rendah / sonoforesis utk

periode wkt singkat (<90 sekon) akan meningkatkan
permeabilitas stratum korneum melalui pengembangan chanel
reversibel mell kulit, shg menghantarkan molekul obatmell rute
transdermaln

The advantage of the ultrasound delivery over micro needle is

that it doesn’t require regeneration of holes in the skin that
might otherwise potentially admit other compounds to go in.

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Some of the leading transdermal delivery-based products

Drug Brand Name

Fentanyl Duragesic
Climara, Vivelle-Dot,
Estradiol
CombiPatch
Clonidine Catapres-TTS
Nitroglycerine Nitro-Dur, Deponit
Nicotine Nicoderm CQ, Nicotrol
Testosterone Testoderm TTS
Ethinylestradiol &
Ortho Evra
Norelgestromin
Scopalamine Transderm Scop
Lidocaine Lidoderm
Tulobuterol Hokunalin

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 Reservoir o

Pengontrol
kecepatan
Lapisan adhesiv

DDS TRANSDERMAL DG DIFUSI TERKONTROL

IMPERPEABLE BACKING
OCCLUSIVE BASEPLATE ADSORBEN
POLIETILEN
Al foil

Adhesive rim

DDS TRANSDERMAL DR MATRIKS DISPERSI

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 Figure 2. The layers that comprise the matrix (drug-in-
adhesive) type of patch. The protective liner is
removed prior to applying the patch to skin.

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 The Androderm systems have six components as shown
(1) metallized polyester/SurlynÒ* (ethylene-methacrylic acid
copolymer)/ethylene vinyl acetate backing film with alcohol
resistant ink,
(2) a drug reservoir of testosterone USP, alcohol USP, glycerin
USP, glycerol monooleate, methyl laurate, sodium hydroxide
NF, to adjust pH, and purified water USP, gelled with carbomer
copolymer Type B NF,
(3) a permeable polyethylene microporous membrane,
(4) peripheral layer of acrylic adhesive surrounding the central,
active drug delivery area of the system. Prior to opening of the
system and application to the skin, the central delivery surface
of the system is sealed with a peelable laminate disc
(5) composed of a five-layer laminate containing polyester /
polyesterurethane adhesive / aluminum foil / polyester-
urethane adhesive/polyethylene. The disc is attached to and
removed with the release liner
(6) a silicone-coated polyester film, which is removed before the
system can be used.

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