SEDIAAN MODIFIED

RELEASE (MODIFIED
RELEASE DELIVERY SYSTEM)

Dhadhang Wahyu Kurniawan

@Dhadhang_WK
LABORATORIUM FARMASETIKA UNSOED
4/16/2013

Pendahuluan

Bentuk sediaan pelepasan dimodifikasi

adalah sistem penghantaran obat (DDS)

yang, berdasarkan formulasi dan desain
produk, memberikan pelepasan obat
dalam bentuk yang dimodifikasi berbeda
dari yang bentuk sediaan konvensional.

Pelepasan obat dapat ditunda atau
diperpanjang.

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Produk Obat Pelepasan-Dimodifikasi

Conventional drug products:
 Tablets, capsules, etc to release the active drug

immediately after administration

Modified drug products

 Drug products which release the active drug from the

product at a controlled rate

Controlled-release drug products

 It is designed for different routes of administration

based on:
1. Physicochemical properties of drugs
2. Pharmacologic properties of drugs
3. Pharmacokinetic properties of drugs
4. Properties of materials used in the dosage
form
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MODIFIED-RELEASE DOSAGE FORM

As one for which the drug-release

characteristics of time course and/or

locations are chosen to accomplish
therapeutic or convenience objectives not
offered by conventional dosage forms

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Terminologi

The following terms have been applied to
extended or sustained drug delivery
systems:
 Controlled-release
 Extended release (ER)
 Sustained-release (SR)
 Timed-release (TR)
 Long-acting (LA)
 Prolonged-action (PA), and
 Sustained-action (SA)
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Produk Obat PelepasanPelepasan-Dimodifikasi

dan Rute Pemberiannya

Oral dosage forms
Extended release: controlled release, sustained
release, prolonged release

Delayed release: Enteric coated

Intramuscular dosage forms
 Depot injections
 Water-immiscible injections (oil)

Subcutaneous dosage forms: Implants

Transdermal delivery systems: Patches,

Creams, Gel, etc.

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Delayed-release products

Biasanya tablet salut enterik atau

kapsul dirancang untuk melewati

lambung tanpa perubahan
(unaltered) untuk melepaskan obat
mereka dalam saluran usus.

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Extended-release products

Dirancang untuk melepaskan obat mereka

dalam cara yang terkendali, pada predetermined rate, durasi and lokasi dalam
tubuh untuk mencapai dan
mempertahankan optimum therapeutic
blood levels of drug.

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Rationale for extended release

pharmaceuticals

Obat yang tidak inheren tahan lama
memerlukan dosis harian ganda untuk
mencapai efek terapi yang diinginkan.

Beberapa dosis harian yang sering merepotkan
dan dapat mengakibatkan dosis yang
terlewatkan, dibuat-up dosis dan pasien noncompliant dengan regimen terapeutik.

Kadar obat dari bentuk sediaan konvensional
lepas-segera yang diambil lebih dari sekali
sehari jadwal pasti biasanya menunjukkan
puncak sekuensial dan palung (lembah) yang
berhubungan dengan dosis masing-masing.
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Rationale for extended release

pharmaceuticals

Tablet atau kapsul yang pelepasannya diperpanjang
biasanya diambil hanya sekali atau dua kali sehari
dibandingkan dengan dosis konvensional yang
biasanya 2 sampai 4 kali sehari

Produk ini dirancang untuk memberikan pelepasan
segera obat yang akan segera menghasilkan terapi
yang diinginkan, diikuti dengan pelepasan bertahap
dan berkesinambungan dari jumlah tambahan obat
untuk mempertahankan efek ini selama periode
waktu yang telah ditentukan.

Kebutuhan untuk dosis obat pada malam hari dapat
dihilangkan
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Keuntungan Sediaan Lepas

Terkendali
1. Mengurangi frekuensi pemakaian obat
2. Menambah/lebih mengenakkan pasien
3. Menghindari/tidak perlu adanya
4.
5.
6.
7.

pemakaian obat pada malam hari

Mengurangi fluktuasi kadar obat dalam
darah
Efek obat yang lebih uniform
Mengurangi iritasi saluran cerna
Mengurangi efek samping
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Kerugian Sediaan Lepas

Terkendali
1. Biaya
2. Korelasi in vitro-in vivo (sering jelek)
3. Dose dumping
4. Mengurangi fleksibilitas pemberian obat
5. Menaikkan kemungkinan first-pass

effect
6. Secara umum, bioavailabilitas kurang baik
7. Efektivitas pelepasan obat dipengaruhi
dan dibatasi oleh GI residence time
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Karakteristik Obat yang

Tidak Cocok Digunakan dalam
Sediaan Lepas Terkendali
1. Waktu paro eliminasi pendek
2. Waktu paro eliminasi panjang
3. IT kecil
4. Dosis besar
5. Absorpsi jelek
6. Absorpsi secara aktif
7. Kelarutan yang kecil
8. First-pass effect yang ekstensif
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Metode Fisika yang Potensial Digunakan

untuk Sediaan LepasTerkendali
1. Kapsul dengan bahan polimer
1. Dapat diisi bahan padat, cair, dan suspensi
2. Pelepasan dikontrol oleh difusi melalui dinding

kapsul

2. Dispersi heterogen partikel dalam matriks

1. Matriks biodegradable atau nonbiodegradabel
2. Pelepasan obat dikontrol oleh:
1. difusi melalui matriks
2. erosi matriks
3. kombinasi keduanya
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Metode Fisika yang Potensial Digunakan

untuk Sediaan LepasTerkendali
3. Pelapisan obat dengan bahan polimer
Obat dilapisi dengan film polimer yang biodegradable
atau nonbiodegradabel
 Kontrol pelepasan oleh:
1. difusi melalui matriks
2. erosi bahan pelapis (film)
3. kombinasi keduanya


4. Dispersi heterogen atau pelarutan obat dalam

matriks hidrogel yang dapat mengembang


Kontrol pelepasan oleh: difusi obat melalui bagian

yang mengembang dari matriks
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Metode Fisika yang Potensial Digunakan

untuk Sediaan LepasTerkendali
5. Obat berada dalam larutan kental polimer


Kontrol pelepasan oleh: difusi perlahan-lahan

melalui polimer atau pengenceran oleh media

6. Ikatan kimia antara obat dengan polimer

(back-bone)



Ikatan ester antara obat dengan polimer

Kontrol pelepasan oleh : hidrolisis ikatan ester

7. Pompa yang dapat melepaskan obat secara

mekanik atau kimiawi


Tekanan osmose menyebabkan air masuk ke dalam

depot obat dan obat dipompa keluar
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Metode Difusi

Metode ini menggantungkan penghantaran

obatnya dari kontrol difusi atau disolusi

Driving force perpindahan molekul obat

adalah gradien konsentrasi; obat bergerak

dari tempat yang berkonsentrasi tinggi ke
tempat yang berkonsentrasi rendah

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Diffusion

Major process for absorption.

No energy required.

Drug molecules diffuse from a region of higher
concentration to lower concentration until
equilibrium is attainded.

Directly proportional to the concentration gradient
across the membrane.

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Polymer for Controlled-Release Delivery

There are several important factors to consider in
selecting or developing a polymer for controlled
delivery:
1.

Biocompatibility and toxicology

2.

Regulatory acceptance or concerns

3.

Degradation rate and degradation products and their

biocompatibility and toxicology, if biodegradable

4.

Cost

5.

Chemical, physical, and mechanical properties

6.

Suitable solvents

7.

Processing requirements

8.

Compatibility limits of the active agent with the polymer

9.

Required sterilization methods

10. Thermal transition temperatures

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Matrix Type

Also called as Monolith

dissolution controlled
system.
Controlled dissolution by:
1.Altering porosity of tablet.
2.Decreasing its wettebility.
3.Dissolving at slower rate.
First order drug release.
Drug release determined by
dissolution rate of polymer.
Examples: Dimetane
extencaps, Dimetapp
extentabs.

Soluble drug

Slowly
dissolving
matrix

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Encapsulation

Called as Coating

dissolution controlled
system.

Dissolution rate of coat
depends upon stability &
thickness of coating.

Masks colour, odour, taste,
minimising GI irritation.

One of the
microencapsulation method
is used.

Soluble drug

Slowly
dissolving
or erodible
coat

Examples: Ornade spansules,

Chlortrimeton Repetabs
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Matrix Diffusion Types

Rigid Matrix Diffusion: Materials used are

insoluble plastics such as PVP & fatty acids.

Swellable Matrix Diffusion

1. Also called as Glassy hydrogels.Popular for

sustaining the release of highly water soluble
drugs.
2. Materials used are hydrophilic gums.
Examples :
 Natural- Guar gum,Tragacanth.

 Semisynthetic -HPMC,CMC,Xanthum gum.

 Synthetic -Polyacrilamides.

Examples: Glucotrol XL, Procardia XL

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Matrix system
Rate controlling
step:
Diffusion of dissolved
drug in matrix.

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Reservoir System

Also called as Laminated matrix device.

Hollow system containing an inner core
surrounded in water insoluble membrane.

Polymer can be applied by coating or
micro encapsulation.

Rate controlling mechanism - partitioning
into membrane with subsequent release
into surrounding fluid by diffusion.

Commonly used polymers - HPC, ethyl
cellulose & polyvinyl acetate.

Examples: Nico-400, Nitro-Bid
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Reservoir System
Rate controlling
steps :
Polymeric content in
coating, thickness of
coating, hardness of
microcapsule.

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Dissolution & Diffusion Controlled

Release system

Drug encased in a partially

soluble membrane.
Pores are created due to
dissolution of parts of
membrane.
It permits entry of aqueous
medium into core & drug
dissolution.
Diffusion of dissolved drug out
of system.
Ex- Ethyl cellulose & PVP
mixture dissolves in water &
create pores of insoluble ethyl
cellulose membrane.

Insoluble
membrane
Entry of
dissolution
fluid
Drug
diffusion

Pore created by
dissolution of
soluble fraction of
membrane

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Osmotic Pressure Controlled Drug

Delivery System

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Osmotic Pressure Controlled Drug

Delivery System
Osmosis
- Movement of solvent from lower to higher concentration.
- The passage of solvent into a solution through
semipermeable membrane.
Semipermeable Membrane
Molecules are permitted only to one component (Water).

Osmotic pressure
It is the hydrostatic pressure produced by a solution in a
space divided by a semipermeable membrane due to
difference in concentration of solutes.
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Osmotic Pressure Controlled

System

Provides zero order release

Drug may be osmotically active, or
combined with an osmotically active
salt (e.g., NaCl).
Semipermeable membrane usually
made from cellulose acetate.
More suitable for hydrophilic drug.
Examples: Glucotrol XL, Procardia XL,

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Osmotic Pressure Controlled

System

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Osmotic Pressure Controlled

System

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Recent Trends : Extended release

formulation of Bupropion

Bupropion is used in the treatment of
major depressive disorder.

Conventional formulation has to be
administered 3 times daily

Initially 150 mg ER formulation was
introduced for bid regimen
Later on 300 mg ER formulation was
introduced for once daily regimen

For ER formulation provide similar Cmax
and AUC values as compared to
immediate release formulation at steady
state.
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Recent Trends: Extended release

formulation of Bupropion

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Recent Trends: OROS

Technology (ALZA corporation)

Single layer tablet: Drug

core (water soluble drug

ELEMENTARY OSMOTIC PUMP
with or without excipients)
Semipermeable membrane
with a drilled orifice
Water imbibition by the core
because of osmotic action
results in drug dissolution,
which is released at a
controlled rate through the
orifice
Not suitable for water insoluble drugs.
Examples: Sudafed 24
hours (Pseudoephedrine); Volmax (Salbutamol) 4/16/2013

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Recent trends: Geomatrix (SKY

Parma)
Products in market:
Cordicant -uno
Madopar DR
SULAR ER

This technology Controls amount,

timing and location of release in
body.
-Formulation with predictable and
reproducible drug release profile.
-Controls rate of drug diffusion
throughout release process,
ensuring 100% release Products
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thank you

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