SISTEM PENGHANTARAN OBAT
PENDAHULUAN
TIM DOSEN TEKNOLOGI FARMASI
SEMESTER GENAP 2023-2024
• CPL
• CPMK
• Sub CPMK -1:
Mahasiswa mampu menjelaskan perkembangan sistem penghantaran dan pelepasan obat
• Integrasi AIK
QS. Al-Mujadalah:11
QS.Al-Alaq:1-5 QS. Al-Maidah:11
SASARAN PERKULIAHAN
1. Teori sistem penghantaran obat/ Drug Delivery System
2. Prinsip teknologi dalam penghantaran sediaan lepas tunda/extended release dosage forms
3. Jenis/bentuk sediaan dengan penghantaran modifikasi/lepas tunda 4. Aplikasi sistem penghantaran sediaan obat
5. Perkembangan teknologi dalam sistem penghantaran obat batasan; jenis; aplikasi
• pharmaceutical formulations or devices that help in achieving
targeted delivery and/or controlled release (CR) of therapeutic agents in our body
Drug Delivery System
• The proper design and formulation of a dosage form requires
consideration of the physical, chemical, and biologic characteristics of
all of the drug substances and pharmaceutical ingredients to be used
in fabricating the product.
• Drug substances are seldom administered alone;
• Combination with one or more nonmedicinal agents that serve varied and specialized pharmaceutical functions
• The drug and pharmaceutical materials must be compatible with one another to produce a drug product that is stable, efficacious,
attractive, easy to administer, and safe
Function of Pharmaceutical ingredients or excipients
• Solubilize,
• suspend,
• thicken,
• dilute,
• emulsify,
• stabilize,
• preserve,
• color,
• flavor, and
• fashion medicinal agents into efficacious and appealing dosage forms
Importance of dosage forms
• To protect the drug substance from the destructive influences of atmospheric oxygen or humidity (coated tablets, sealed ampuls)
• To protect the drug substance from the destructive influence of gastric acid after oral administration (enteric-coated tablets)
• To conceal the bitter, salty, or offensive taste or odor of a drug substance (capsules, coated tablets, flavored syrups)
• To provide liquid preparations of substances that are either insoluble or unstable in the desired vehicle (suspensions)
• To provide clear liquid dosage forms of substances (syrups, solutions)
Cont…
• To provide rate-controlled drug action (various controlled-release tablets, capsules, and suspensions)
• To provide optimal drug action from topical administration sites
(ointments, creams, transdermal patches, and ophthalmic, ear, and nasal preparations)
• To provide for insertion of a drug into one of the body’s orifices (rectal or vaginal suppositories)
• To provide for placement of drugs directly in the bloodstream or body tissues (injections)
• To provide for optimal drug action through inhalation therapy (inhalants
and inhalation aerosols)
Factor to consider in dosage form design
• Preformulation
• Biopharmaceuticals Consideration
• Route administration
• Drug factors in dosage forms design
• Particle size/surface area
• Solubility
• Dissolution
• Partition coefficient PKA
• Crystal properties polymorphism
• Stability
• Organoleptic property
• Therapeutic consideration
Classification of dosage form
Based on route of administration
Based on physical presentation
Route of adminstration
• Oral
• Sublingual
• Parenteral (intravenous, intramuscular,
subcutaneous, intradermal, and intraperitoneal)
• Pulmonary
• Nasal
• Ocular/otic
• Dermal/topical
• Vaginal
• Rectal
Physical presentation
Solid
• Capsule (Hard and soft capsule)
• Tablet (enteric, chewable, buccal/sublingual)
• Pellet
• Pill
• Lozenges
• Spray
Liquid
• Monophasic (homogenous mixture in one phase)
• Biphasic (Suspension and
emulsion)
First pass metabolism (thing to consider)
The importance of preformulation study
• A Preformulation study is an investigation of the physical, chemical, and mechanical properties of a drug substance to develop a safe, effective, and stable dosage form.
• Preformulation is the first step in the rational formulation of an active pharmaceutical ingredient (API).
• It is an investigation of the physicochemical properties of the drug substance, alone and in combination with excipients.
• The overall concept of preformulation is to create useful information which can be used by the innovator and/or industry to develop a stable formulation and marketable Drug Delivery System (DDS)
The objectives of
preformulation study
To establish the physicochemical
properties of the new drug substance To determine its kinetic profile and stability
To determine its compatibility with inactive ingredients or excipients
To know the methods of drug
processing and storage
Preformulation tests according to dosage form
ORGANOLEPTIC PROPERTIES
PURITY OF API AND EXCIPIENTS
• API with impurities is not always necessary to be rejected, provided that the impurity is completely characterized.
• The major concern is that impurities can affect product stability. Impurity is often found to be carcinogenic in nature, e.g. aromatic amine (p- amino phenol).
Classification of impurities (ICH, 2008)
1. Organic impurities (process- and drug-related) Starting materials
By-products Intermediates
Degradation products
Reagents, ligands, and catalysts 2. Inorganic impurities
Reagents, ligands and catalysts
Heavy metals or other residual metals Inorganic salts
Other materials (e.g., filter aids, charcoal) 3. Residual solvents
PENGGOLONGAN BERDASARKAN PENGHANTARAN
konvensional - pelepasan zat aktif segera/immediate release
- delayed-release -repeated-release -controlled-release -sustained-release Lepas tunda
Extended – release dosage forms
sediaan yang pelepasan zat aktifnya diatur melalui sistem penghantaran tertentu dan mengalami proses teknologi tertentu pula
Parameter :
• jumlah obat yang dihantarkan
• laju penghantaran dan pelepasan
Drug release
• CR: Controlled release, SR: sustained release, IR: immediate release. MTC: Minimum Toxic concentration, MEC: Minimum effective concentration (Maiti and Sen, 2017)
PENGHANTARAN SEDIAAN MODIFIED RELEASE
• Oral
• Kolon
• Mukosal
• Nasal/Pulmonary
• Okular
• Transdermal
• Sistem Saraf Pusat/Blood Brain Barrier
• dll
TUJUAN PEMBERIAN
1. Mengurangi frekuensi pemberian obat; menghindari kesalahan penggunaan atau kehilangan dosis 2. Mengurangi frekuensi penyuntikan;
menghilangkan rasa nyeri/infeksi pada lokasi penyuntikan
3. Mempertahankan konsentrasi obat pada tingkat terapetik selama periode waktu tertentu
4. Mengurangi kerugian yang dapat bersifat toksik atau efek samping lainnya yang timbul segera setelah pemberian obat
5. Memperoleh aksi farmakologi yang konstan,sekalipun utk senyawa dengan t½ biologis yang pendek
6. Mengurangi jumlah zat aktif yang dibutuhkan untuk pengobatan melalui pengurangan konsentrasi yang cenderung tinggi
7. Mengurangi resiko resisten untuk keadaan saat kadar darah dibawah konsentrasi minimal antibakteriostatik
Teknologi → modifikasi formulasi
zat aktif
(karakterisasi/sifat
fisika kimia) Eksipien
Proses
Conclusion
• Preformulation scientists act as mediators between synthetic chemists and formulation scientists. With a holistic aim of designing and developing a
stable, cost-effective and therapeutically sound patient-friendly dosage form, they reduce the burden of formulation scientist and help the pharmaceutical industries to avoid unforeseen consequences. The right selection of API,
excipients, dosage form, manufacturing processes, packaging materials,
analytical methods and storage conditions among many others are important for the benefit of the product’s life cycle and usage.
