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Sel-sel yang cepat mengadakan proliferasi terdiri 5 lapisan yang berbeda, dari dalam ke luar: 1. stratum germinativum (basal) 2. stratum spinosum (prickle) 3. stratum granulosum (granular) 4. stratum lucidum (lucid) 5. stratum korneum Selain stratum korneum, lapisan-lapisan mempunyai sel-sel yang hidup

Transdermal drug delivery is an approach used to deliver drugs through the skin for therapeutic use as an alternative to oral, intravascular, subcutaneous, and transmucosal routes.

1. 2. 3. 4.

5.
6. 7. 8.

Local application formulations, e.g., transdermal gels Penetration enhancers Drug carriers, e.g., liposomes and nanoparticles Transdermal patches Transdermal electrotransport Use of physical modalities to facilitate transdermal drug transport Minimally invasive methods of transdermal drug delivery, e.g., needle-free Injections

a.

b.

Transdermal delivery system (patch) is easy to use Used for lipid soluble drugs with low dose and low MW

Kerugian : a. Some irritation by patch or drug b. Permeability of skin variable with condition, anatomic site, age, and gender c. Expensive

Type Synthetic surfactants

Examples Laureth-9 sodium lauryl sulphate polysorbate 20 and 80 PEG-8 laurate sorbitan laurate glyceryl monolaurate saponins (e.g., Quillaja saponins) sodium deoxycholate sodium glycocholate sodium fusidate sodium taurodihydrofusidate

Mechanism of action membrane interaction extraction of membrane proteins and lipids solubilization of peptides

Bile salts

denaturation of proteins decrease of mucus viscosity decrease of peptidase activity solubilization of peptides formation of reversed micelles fosfolipid acylchain disruption

Fatty acids and derivatives

oleic acid caprylic acid lauric acid Palmitoylcarnitine Na2EDTA citric acid Salicylates cyclodextrins and derivatives

Chelators

Ca2 complexation (influencing tight junctions)

Inclusion complexes

Other agents

Azone

increasing peptide stability increasing solubility enzyme inhibition lipid structure disruption

Transdermal scopolamin (prevent travelrelated motion sickness) Transdermal nitroglycerin (prophylactic treatment of angina) Transdermal clonidin (for hypertensi) Transdermal estradiol Transdermal testosterone

Drugs have been administered nasally for several years both for topical and systemic effect. Topical administration includes agents for the treatment of nasal congestion,rhinitis, sinusitis, and related allergic and other chronic conditions. Various medications include corticosteroids, antihistaminics, anticholinergics, and vasoconstrictors.

1.High permeability of the nasal mucosa, compared with the epidermis or the gastrointestinal mucosa 2. Highly vascularized subepithelial tissue 3. Rapid absorption, usually within half an hour 4. Avoidance of first pass effect that occurs after absorption of drugs from the gastrointestinal tract 5. Avoidance of the effects of gastric stasis and vomiting, for example, in migraine patients 6. Ease of administration by the patients, who are usually familiar with nasal drops and sprays 7. Higher bioavailability of the drugs than in the case of gastrointestinal route or pulmonary route 8. Most feasible route for the delivery of peptides

1. Diseases conditions of the nose may result in impaired absorption. 2. Dose is limited because of relatively small area available for absorption. 3. Time available for absorption is limited. 4. Little is known of the effect of common cold on transnasal drug delivery, and it is likely that instilling a drug into a blocked nose or a nose with surplus of watery rhinorrhea may expel the medication from the nose. 5. The nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration because of poor membrane permeability, rapid clearance, and enzymatic degradation into the nasal cavity.

Factors that influence drug delivery to colorectal area: 1. The rate of absorption of drugs from the colon is influenced by the rate of blood flow to and from the absorptive epithelium. 2. Dietary components such as complex carbohydrates trap molecules within polysaccharide chains. 3. Lipid-soluble molecules are readily absorbed by passive diffusion. 4. The rate of gastric emptying and small bowel transit time. 5. Motility patterns of the colon determine the rate of transit through the colon and hence the residence time of a drug and its absorption. 6. Drug absorption varies according to whether the drug is

1. A relatively large amount of the drug can be administered. 2. Oral delivery of drugs that are destroyed by the stomach acid and/or metabolized by pancreatic enzymes. 3. This route is safe and convenient particularly for the infants and the elderly. 4. This route is useful in the treatment of emergencies such as seizures in infants when the intravenous route is not available. 5. The rate of drug absorption from the rectum is not influenced by ingestion of food or rate of gastric emptying. 6. The effect of various adjuvants is generally more effective in the rectum than in the upper part of the gastrointestinal tract. 7. Drugs absorbed from the lower part of the rectum bypass the liver. 8. Degradation of the drugs is much less in the rectal lumen than in the upper gastrointestinal tract.

1. Some hydrophilic drugs such as antibiotics and peptide drugs are not easily absorbed from the rectum and absorption enhancers are required. 2. Drugs may cause rectal irritation and sometimes proctitis with ulceration and bleeding.

Hormon, peptida, dan protein tidak cocok untuk pemberian obat melalui mulut, sehingga kebanyakan diberikan secara parenteral. Keunggulan formulasi peptida dan protein antara lain : Memperbaiki stabilitas secara fisika dan kimia Memperpanjang waktu paro Meningkatkan laju absorpsi Mengurangi terjadinya metabolisme

Gastric retensive system

Colonic delivery system

Penambahan bahan/senyawa untuk memperlama bertahan di lambung Sistem bioadhesive

Polimer yang spesifik pada pH usus

Transit time di usus diperlama

Sistem sediaan floating

Polimer sensitif dengan bakteri pada kolon

Pharmacology, particularly pharmacokinetics and pharmacodynamics, have traditionally influenced drug delivery formulations. Some of the newer developments in pharmacology and therapeutics that influence the development of DDSs are as follows: 1. Pharmacogenetics 2. Pharmacogenomics 3. Pharmacoproteomics 4. Pharmacometabolomics 5. Chronopharmacology

Use of recombinant DNA technology Expansion of use of protein and peptide drugs in current therapeutics Introduction of antisense, RNA interference, and gene therapy Advances in cell therapy: introduction of stem cells Miniaturization of drug delivery: microparticles and nanoparticles Increasing use of bioinformatics and computer drug design A trend toward development of target-organ-oriented dosage forms Increasing emphasis on controlled-release drug delivery Use of routes of administration other than injections Increasing alliances between pharmaceutical companies and DDS companies

Mencari jurnal ilmiah internasional tahun jurnal > 2009 Diketik dengan huruf arial ukuran 12 di kertas A4 Masing-masing kelas dijilid jadi 1 dan dikumpulkan paling lambat tanggal 11 Nopember 2011 Setiap pertemuan untuk diskusi 2 atau 3 kelompok Setiap kelas dibagi menjadi 12 kelompok (2 kelompok membuat dengan materi sama)

Oral DDS terdiri dari:

1. 2. 3. 4. 5. 6.

Sistem Sistem Sistem Sistem Sistem Sistem

floating non effervescent floating effervescent osmotic pump with osmogen osmotic pump matriks larut (soluble matrix) matriks tidak larut (insoluble matrix)

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2.
3. 4. 5. 6.

Oral DDS Sistem membran reservoir Oral DDS Sistem mucoadhesive Oral DDS Sistem enterik Nasal DDS (Gel dosage form) Nasal DDS (Spray dosage form) Inhalasi DDS

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2.
3. 4. 5. 6.

Transdermal DDS Transdermal DDS with patch Colon targetted DDS Liposom DDS Nanopartikel DDS Buccal adhesive DDS