MEKANISME TRANSPOR

SEDIAAN TOPIKAL
 TUJUAN MEMPELAJARI FORMULASI DAN
TEKNOLOGI SEDIAAN SEMISOLIDA

 Memahami konsep-konsep bagaimana

memformulasi sediaan semisolida

 Memahami pembuatan sediaan semisolida

atas dasar karakteristik fisikokimia bahan-
bahan dan target yang dikehendaki

 Memahami mutu dan kontrol kualitas

sediaan semisolida
 CARA PEMBERIAN OBAT

Peroral Kojungtival Intra Respiratori

Sublingual Intraokular Rektal

Parenteral Vaginal

Perkutan Intranasal Urethral

DERMAL APPLICATION
 LIKUIDA

BENTUK SEDIAAN
/DOSAGE FORM SEMISOLIDA

SOLIDA

TUJUAN TERAPI

LOKAL SISTEMIK
 FORMULASI OBAT
UNTUK PENGGUNAAN DI KULIT

LOKAL
KONTAK
TUJUAN
DENGAN KULIT

SISTEMIK

ANATOMI FISIOLOGI
KULIT
THE MAIN FUNCTIONS OF SKIN (BARRY, 1983)
1. To maintain body fluids and tissues  the mechanical function.
2. To protect from potentiallyharmful external stimuli  the
protective or barrier function: (a) microorganism; (b)
chemicals; (c)radiation; (d) heat; (e) electrical barrier; (f)
mechanical shock.
3. To receive external stimuli, i.e., to mediate sensation: (a) tactile
(pressure); (b) pain; (c) heat.
4. To regulate body temperature.
5. To synthesize and to metabolize compounds.
6. To dispose of chemical wastes (glandular secretaions).
7. To provide identification by skin variations.
8. To attract the opposite sex (apocrine secretaions are
evolutionarily defunct in this role).
9. To regulate blood pressure.
Komponen epidermis dan dermis kulit
A. Epidermis :

- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
Deferensiasi epidermis
Stratum corneum

- Tebal  10-20 µm
- Non viable epidermis
- Diameter sel ± 40 µ
- Sel terdiri dari keratin ~ 70%, lipid ~20%
- Kandungan air 15-20%
- Solut dengan diameter  0,1 µm
dapat melewati stratum korneum
- Tiap 2-3 minggu mengelupas
LIPID CONTENT OF THE STRATUM CORNEUM
INTERCELLULAR SPACE

Lipid % (w/w) mol %

Cholesterol ester 10.0 7.5 a

Cholesterol 26.9 33.4
Cholesterol sulfate 1.9 2.0
Total cholesterol derivatives 38.8 42.9
Ceramide 1 3.2 1.6
Ceramide 2 8.9 6.6
Ceramide 3 4.9 3.5
Ceramide 4 6.1 4.2
Ceramide 5 5.7 5.0
Ceramide 6 12.3 8.6
Total ceramides 41.1 29.5
Fatty acids 9.1 17.0 a
Others 11.1 10.6 b

aBased on C16 alkyl chain.

bBased on MW of 500.
AMINO ACIDCOMPOSITION OF NAIL, HAIR, AND STRATUM CORNEUM

Amino acid Nail Hair Stratum corneum

Lysine 3.1a 2.5a 4.2a
Histidine 1.0 0.9 1.5
Arginine 6.4 6.5 3.9
Aspartic acid 7.0 5.4 7.9
Threonine 6.1 7.6 3.0
Serine 11.3 12.2 13.6
Glutamic acid 13.6 12.2 12.6
Proline 5.9 8.4 3.0
Glycine 7.9 5.8 24.5
Alanine 5.5 4.3 4.4
Valine 4.2 5.5 3.0
Methionine 0.7 0.5 1.1
Isoleucine 2.7 2.3 2.7
Leucine 8.3 6.1 6.9
Tyrosine 3.2 2.2 3.4
Phenyl alanine 2.5 1.7 3.2
Half-cysteine 10.6 15.6 1.2
Sulfur 3.2%b 4.5%b 1.4%b
aExpressed asresidues per 100 residues.
bExpressed as % dry weight (Walters, 2002)
B. Dermis:
Merupakan komponen kritis tubuh,
berfungsi sebagai pensuport nutrisi, kekebalan
(imun) dan sistim lain pada epidermis.
Terdiri dari:
- Pembuluh darah
- Kelenjar keringat
- Glandula sebasea
- Kantung rambut
- Otot penegak
C. Jaringan
Subkutan/hipodermis
Berfungsi sebagai :
- Isolator panas
- Peredam schock
- Penyimpan energi

Terdiri dari sel lemak

yang tersusun dalam lobus
dan berikatan dengan
dermis dengan bantuan
kolagen dan elastin fiber
 Peran utama subkutan adalah tempat
pembuluh/vascular dan sistem syaraf
kulit

C. Skin Appendages.
- Kantung rambut/ hair folicle
- Kelenjar keringat/ eccrine sweat gland
- Kelenjar getah lain/ apocrine sweat gland
- Kuku
 APPENDAGES ASSOCIATED WITH THE SKIN
APPENDAGE

Parameter Hair follicle and Ecrine gland Apocrine gland Nails

sebaceous gland

Function Protection (hair) and Cooling Vestigal secondary sex Protection

Lubrication (sebum) gland ?
Distribution Most of the body Most of the body Axillae, nipples, anogenital End of fingers
and toes
Average/cm2 57-100 100-200 Variable -
Fractional Area 2.7 X 103 104 Variable -
Secretons Sebum Sweat (dilute saline) “Milk” protein, lipoprotein, Nil
lipid
Secr. Stimulated by Heat (minor) Heat, cholinergic Heat -
Biochemical innervation - Cholinergic Cholinergic (?) -
of gland response
Control Hormonal Sympathetic nerves Sympathetic nerves -
 LIPID COMPOSITION OF HUMAN SEBUM

Lipid Lumen of glanda Skin surfacea

Squalene 15 15
Wax esters 25 25
Cholesteryl esters 2 2
Triglycerides 57 42
Fatty acids 0 15 b
Cholesterol 1 1

aExpressed as weight%.
bMost abundand fatty acid in human sebum is C
16:1.
Source: Cortesy of P.Wertz (Walters, 2002)
RUTE PENETRASI
 Rute of penetration of drug

Schematic representation of stratum corneum and

its intercellular and transcellular pathways of drug
permeation.
MEKANISME TRANSPOR PERKUTAN
INTERFACIAL BOUNDARIES PENETRATION ROUTES SOME TREATMENTS

DRUG DISSOLVES,
DIFFUSES, RELEASES Protective Layer
SURFACE
FROM VEHICLE Insect Repellent

TRANSEPIDERMAL
Emolliency
STRATUM Partition, diffusion, Exfolients
CORNEUM Stratum Corneum
TRANSAPPENDAGEAL
Antiperspirant
APPENDAGES Exfolient
Pilosebaceous Ecrine Gland Antibiotic
Depilatory

VIABLE
EPIDERMIS Partition, Diffusion, Anti-Inflamantory
Viable Epidermis Anaesthetic
Antipruritic
Antihistamin
Partition, Diffusion,
DERMIS Dermis

CIRCULATION Removal via Transdermal system

circulation nitroglycerin
FAKTOR YANG MEMPENGARUHI PENETRASI
KULIT DAN ABSORPSI BAHAN AKTIF

FAKTOR BIOLOGI

-Umur

-Kondisi kulit

-Tempat pemakaian

-Metabolisme kulit

-Perbedaan spesies
FAKTOR FISIKO KIMIA

1. Konsentrasi solut dalam pembawa

2. Interaksi antara obat dan pembawa
3. Hidrasi kulit
4. Adanya enhancer
5. Interaksi antara obat dan kulit 
Koefisien distribusi bahan aktif antara
basis dan kulit.
6. Koefisien partisi (log P) bahan aktif
7. BM bahan aktif  ukuran partikel
MEKANISME ENHANCER

1. Meningkatkan permeabilitas kulit

terhadap obat dengan menyebabkan
perubahan yang bersifat reversible
pada stratum corneum

2. Meningkatkan aktivitas termodinamika

obat jika enhancer berfungsi sebagai
kosolven.
3. Meningkatkan koefisien partisi obat
sehingga pelepasan obat dari
pembawa dan masuk kedalam kulit
meningkat.

4. Meningkatkan difusi obat dengan cara

hidrasi stratum corneum.
 Enhancer Example

A. Established enhancer

1. Sulfoxide and Dimethylsulfoxide

similar compound Dimethyl acetamide
Dimethylformamide
N-methylformamide

2. Pyrolidones 2-Pyrrolidone
1-methyl 2-pyrrolidone
5-methyl 2-p yrrolidone
1,5 dimethyl 2-pyrrolidone
1 ethyl 2-pyrrolidone
3. Fatty acids Oleic acid, Lauric acid
Linolic acid, Myristic
acid

Azon or Laurocapram and its derivatives

5. Urea

6. Surfactant
anionic Sodium lauryl sulfate
cationic Trimethyl ammonium
nonionic bromide
Synperonic NP series
7. Alcohol Ethanol
Lauryl alcohol
Linolenyl alcohol
Octanol

8. Glycols Propylene glycol

Polyethylene glycol 400

B. Under investigation

1. Terpenes and Menthol and Camphor

terpenoids
2. n-Pentyl N-acetylprolinate
3. Lactam N-acetic acid esters
TOPICAL AGENTS USED IN DERMATOLOGY

A. Germicides and antibacterial agents

1. General :
phenol, alcohol, aldehides, acids, surfactants,
etc
2. Topical antibiotics:
penicillin, streptomycin, neomycin, tetracyclin HCl,
erythromycine, clindamycine
3. Topical anti fungal:
sodium propionat, benzoic acid, salicylic acid,
tolnaftalent
4. Insect repellents and parasiticides:
dimethyl pthalate, benzoic benzoate
B. Antihistamines
diphenhydramine HCl, chlorcycline HCl,
mepyramine maleate

C. Antipruritics
ametocaine, benzocaine, cocaine (ester), cinchocaine
others: benzyl alcohol, camphor, menthol etc

D. NSAIDs
Diclofenac acid, indomethazine, piroxicam etc
E. Anti-inflammatory agents

GROUP I clobetasol propionate 0,05%

Extremely potent
GROUP II betamethasone valerate 0,1%
potent fluonicolon acetonide 0,025%
triamcinolone acetonide
0,025% - 0,1%

GROUP III clobetasol butyrate 0,05%

Moderately dexamethasone 0,1%
potent
GROUP IV Hydrocortisone
Less potent alcohol/acetat 0,1-2,5%
Methyl prednisone 0,025%
F. Cytotoxic agents
5-fluoracil, methotrexate, colchocine

G. Antiperspirants
aluminium chloride, aluminium hydroxide

H. Astringents
Tanin, Al dan Zn salts etc

I. Keratolytics and caustics

Benzoic, salicylic acid, resorcinol, AHA

J. Keratoplastics agents
coaltar, tertinoin
K. Rubifacients
nicotinates (methyl, ethyl, etc)
essentiale oils (terpentine, cayuputi, capsicum)

L. Pigmenting and depigmenting agents

psoralene, hydroquinone

M. Sunscreen
titanium dioxide, PABA, cinnamates,
benzophenone, etc

N. Epilatories and depilatories

wax, strontium/barium sulfide, thioglycolic acid

O. Miscelaneous
emolients: oil, hydrocarbon, waxes
surfactants: anionic, cationic, nonionic, amfoteric
 PUSTAKA
1. Barry B.W., 1983. Dermatological Formulations.
Percutaneous Absorptions. Series of Drugs And
Pharmaceutical Sciences Vol. 18. Marcel Dekker, Inc.,
New York and Basel.

2. Martin A., Swarbick J., Cammarata A., 1983. Physical

Pharmacy 3rd Ed. Lea and Febiger, Philadelphia.

3. Walters K.A., 2002. Dermatological and Transdermal

Formulations. Series of Drugs And Pharmaceutical
Sciences Vol. 119, Marcel Dekker, Inc., New York.

4. Panchagnula R., 1997. Transdermal Delivery of drugs,

Indian J. of Pharmacol., 29:140-156.