PERANCANGAN BENTUK

OBAT
Hudan Taufiq
Bagian Farmakokimia FK UNISSULA
Sasaran Belajar
• Mahasiswa mampu menjelaskan cara merancang bentuk
obat
• Mahasiswa memahami perancangan pemakaian obat
sesuai dosis pada saat pemakaian klinis
• Mahasiswa mampu memahami rancangan “soft drug” dan
“pre drug”
Referensi
• Abraham, D.J. 2003, Burgers Medicinal Chemistry & Drug
Discovery, 6th edition, Volume 1, John Wiley and Sons
Inc., Virginia Commonwealth University.
• Siswandono and Sukardjo, B. 2008, Kimia Medisinal,
Surabaya, Airlangga University Press.
• Nogrady, T. and Weaver D. F. 2005, Medicinal Chemistry:
A Molecular and Biochemical Approach, 3rd edition Oford
University Press, New York
• Siswandono and Sukardjo, B. 1998, Prinsip-Prinsip
Rancangan Obat, Surabaya, Airlangga University Press.
RANCANGAN BENTUK
OBAT
Fasa Farmasetik
• Obat (basa/asam lemah)  absorbsi difusi pasif
• Obat terabsorbsi  bentuk molekul (lipofilitas, pKa, pH
lingkungan)
• Penting!!!
• Sifat molekul obat (kestabilan)
• Formulasi
• Bentuk sediaan
• Kloramfenikol tablet
General considerations in dosage form
design
Desired features
• Drug release profile
• Bioavailability
• Clinical effectiveness
API Property Classification –
inter-dependencies between ‘groupings’
 Design of a Paediatric Dosage Form (1)

Define API(s) and dosage regime

Development
pharmaceutics; Consider – route of administration
formulation and - suitable dosage form
manufacturing plan

What are pharmacokinetic Determine relevant properties of

characteristics of API(s)?) API(s)
- t50, Cmax, AUC - physicochemical, crystallographic
- BCS (for oral products - stability under ‘stress’ conditions
- BA/BD issue - compatibility with second API
and/or common excipient

Select dosage form and strength -

11 | Peter York | April 2008

 Design of a Paediatric Dosage Form (2)

Sources of Selection dosage form and strength

information
Innovator literature Consider suitable formulations and
manufacturing processes
Company
experience
Other literature Prototype formulations and
sources Testing
manufacturing route,
and prototype packaging Phys/chem
stability
(Dissolution)
Define ‘design
space’, process
Optimisation techniques DoE
Validation (formulation and Relevant product
control AI
tests
Manufacturing process) tools
(Pilot BE study)

Selection final formulation

12 | Peter York | April 2008

 Design of a Paediatric Dosage Form

Select final formulation,

manufacturing process
and packaging

Process scale-up studies/batches

Confirmatory stability (dissolution) studies
(BE study)

Documentation for prequalification/ registration dossiers

13 | Peter York | April 2008

PENENTUAN DOSIS PADA
EVALUASI KLINIK
“SOFT” DRUG & PRE-
DRUG
 Soft drug
• Turunan obat aktif secara biologis  sesudah menimbulkan
efek  dirancang pecah pada tubuh  non toksik dan inaktif
• Contoh:
• piridostigmin  penghambat kolinesterase (toksisitas >>>).
• Obat lunak : efek = neostigmin.
• Hiperkolesterolemik (tikus)  total kolesterol dan LDL ↓ 40%  toksisitas
<<<
• Hidrolisis enzimatik
Pra obat
• Zimogen (dihasilkan pankreas, inaktif)  prekursor enzim
-kimotripsin, tripsin, elastase duodenum (enzim
proteolitik  enzim aktif)  hidrolisis ikatan peptida.
-kimotripsin
• Ikatan peptida: pada sisi karboksil (triptofan, tirosin,
fenilalanin) >>> residu hidrofob (leusin, metionin)
• Substrat lain: Ester dan turunan amida dari triptofan,
tirosin, dan fenilalanin
• Contoh: p-nitrofenilasetat
 Tripsin
• Hidrolisis ikatan peptida turunan ester dan amida dari
arginin dan lisin.
Elastase
• Turunan asam amino yang tak bermuatan dan asam
amino rantai samping non aromatik (glisin, alanin, valin,
leusin, serin)
Karboksilesterase (hati, ginjal, duodenum, otak)
• Hidrolisis ester-ester tidak khas dibanding -kimotripsin
dengan kecepatan 104-105
Lipase pankreas (dalam sal.cerna)
• Ester yang tak larut sempurna dalam air