DAFTAR ISI

HALAMAN PENGESAHAN ...........................................................................i

HALAMAN PERNYATAAN ...........................................................................ii

KATA PENGANTAR .......................................................................................iii

DAFTAR ISI .......................................................................................................v

DAFTAR TABEL ..............................................................................................ix

DAFTAR GAMBAR .........................................................................................x

DAFTAR LAMPIRAN .....................................................................................xii

INTISARI ...........................................................................................................xiii

ABSTRACT .........................................................................................................xiv

BAB I PENDAHULUAN .................................................................................1

A. Latar Belakang Penelitian ........................................................................1

B. Rumusan Masalah ....................................................................................3

C. Keaslian Penelitian ..................................................................................4

D. Tujuan Penelitian .....................................................................................5

BAB II TINJAUAN PUSTAKA ......................................................................6

A. Tinjauan Pustaka .....................................................................................6

1. Sediaan transdermal ........................................................................6

2. Anatomi tulit ...................................................................................7

3. Penetrasi obat melalui kulit ............................................................9

4. Kuantifikasi transpor .......................................................................12

5. Chemical Penetration Enhancer (CPE) ............................................15

6. Iontoforesis ........................................................................................16

7. Prometazin HCl .................................................................................18

8. Tween 80 ...........................................................................................20

9. Propilen glikol ...................................................................................21

10. Alat uji difusi in vitro .....................................................................22

11. Analisis berdasarkan model kompartemen .....................................23

12. Factorial design ...............................................................................26

13. Evaluasi dengan goodness of fit .......................................................26

B. Landasan Teori ......................................................................................28

C. Hipotesis .................................................................................................30

D. Rencana Penelitian .................................................................................30

E. Variabel Penelitian .................................................................................31

BAB III METODE PENELITIAN .................................................................32

A. Bahan .....................................................................................................32

B. Alat ........................................................................................................ 32

C. Jalannya Penelitian .................................................................................33

1. Preparasi kulit tikus ..........................................................................34

2. Pembuatan dapar sitrat isotonis pH 5,0 .......................................34

3. Pembuatan larutan dapar fosfat isotonis pH 7,4 ........................34

4. Penetapan panjang gelombang maksimal prometazin HCl dalam dapar fosfat pH 7,5 Isotonis ...........................................................35

5. Validasi penetapan kadar prometazin HCl ......................................35

6. Persiapan peralatan iontoforesis .....................................................35

7. Percobaan penetrasi sesuai factorial design ..................................36

8. Uji permeasi secara in vitro.............................................................38

D. Analisis Data .........................................................................................38

BAB IV HASIL DAN PEMBAHASAN .......................................................40

A. Validasi Metode Penetapan Kadar ......................................................40

1. Penentuan panjang gelombang maksimum prometazin HCl dalam bufer pospat isotonis pH 7,4 ......................................40

2. Validasi metode analisis .................................................................41

B. Hasil Uji Penetrasi ...............................................................................44

1. Hasil uji penetrasi prometazin HCl tanpa enhancer, enhancer PG 5% dan Tween 80 1% serta iontoforesi 0,5 mA/cm2 ...................................................................................44

2. Hasil uji penetrasi prometazin HCl sesuai dengan faktorial design .............................................................................47

C. Analisis dengan Modeling Kompartemen ..........................................49

1. Analisis data dengan WinSAAM .................................................49

2. Prediksi in vivo sediaan transdermal prometazin HCl .................56

3. Parameter transpor transdermal prometazin HCl ..........................58

D. Analisis dengan Factorial Design ........................................................60

1. Analisis terahadap parameter Cp maks ......................................60

2. Analisis terhadap parameter AUC ..............................................61

3. Analisis terhadap parameter AD .................................................63

4. Penentuan kondisi uji optimal teoritis ........................................64

BAB V KESIMPULAN DAN SARAN .......................................................70

A. Kesimpulan ..........................................................................................70

B. Saran ....................................................................................................70

DAFTAR PUSTAKA ...................................................................................71

LAMPIRAN ..................................................................................................75

DAFTAR TABEL

Tabel 1.Kondisi uji berdasarkan factorial design ..............................................37

Tabel 2.Komposisi sediaan uji pada kompartemen donor ................................37

Tabel 3.Hubungan antara konsentrasi prometazin HCl dalam larutan dapar fosfat isotonis pH 7,4 dan absorbansi ..........................................43

Tabel 4.Parameter Cp maks masing-masing kondisi uji .....................................59

Tabel 5.Parameter AUC masing-masing kondisi uji............................................59

Tabel 6.Parameter AD masing-masing kondisi uji .............................................60

Tabel 7.Penentuan kondisi uji optimal ...............................................................65

Tabel 8.Kemungkinan kondisi uji optimal .........................................................66

Tabel 9.Perbandingan respon teoritis dan respon percobaan ..............................69

DAFTAR GAMBAR

Gambar 1.Anatomi kulit (Walters dan Roberts, 2002) .............................8

Gambar 2. Skema penetrasi obat melalui kulit (Banga, 1998) ..................10

Gambar 3. Profil penyerapan molekul yang berdifusi melalui kulit ...........14

Gambar 4.Skema iontoforesis dengan sistem elektroda Ag/AgCl (Kalia dkk., 2004) ....................................................................18

Gambar 5.Strktur kimia prometazin hidroklorida ....................................19

Gambar 6.Struktur molekul Tween 80 ......................................................20

Gambar 7.Struktur kimia propilen glikol .................................................21

Gambar 8.Alat difusi Franz Cel like tipe vertikal .....................................23

Gambar 9.Skema transfer massa model dua kompartemen pada iontoforesis .......................................................................24

Gambar 10.Skema transfer massa model tiga kompartemen ....................25

Gambar 11.Spektra uv-vis prometazin HCl dalam dapar fosfat isotonis pH 7,4................................................................................................40

Gambar 12.Kurva baku prometazin HCl (dalam pelarut dapar fosfat isotonis pH7,4) dan absorbansi ..................................................42

Gambar 13.Profil prometazin HCl yang tertranspor melintasi membran tanpa enhancer, enhancer PG 5% dan Tween 80 1% serta iontoforesi 0,5 mA/cm2 ..............................................................44

Gambar 14.Profil penetrasi prometazin HCl dengan enhancer dan kombinasi sesuai factorial design (n=3) ....................................48

Gambar 15.Contoh listing WinSAAM data transpor prometazin HCl ........50

Gambar 16. Listing WinSAAM data transpor prometazin HCl sudah fix......51

Gambar 17.Skema model kompartemen transpor prometazin HCl..............52

Gambar 18. Hasil curve fitting data individual.............................................53

Gambar 19.Kurva hubungan antara Qo vs Qc formula ac rep.1..................54

Gambar 21.Kurva hubungan antara waktu vs weight residual formula ac rep.1..........................................................................................55

Gambar 21.Kurva hubungan antara Qo vs weight residual formula ac rep.1.............................................................................................55

Gambar 22.Listing WinSAAM untuk memprediksi transpor prometazin HCl in vivo..................................................................................56

Gambar 23.Model kompartemen yang digunakan untuk prediksi profil in vivo..............................................................................................57

Gambar 24.Prediksi profil transpor in vivo prometazin HCl menggunakan WinSAAM.................................................................................58

Gambar 25.Contour plot dari parameter Cp maks dengan iontoforesis konstan.......................................................................................67

Gambar 26.Contour plot dari parameter AUC dengan iontoforesis konstan68

Gambar 27.Contur plot dari parameter AD dengan iontoforesis konstan.....68

DAFTAR LAMPIRAN

Lampiran 1.Certificate of analysis prometazin HCl ......................................75

Lampiran 2.Hasil pengukuran absorbansi,presisi dan akurasi .....................76

Lampiran 3.Contoh parameter fix dan data WinSAAM .................................82

Lampiran 4.Hasil perbandingan sebelum dan sesudah fix ...........................83

Lampiran 5.Kurva hasil fitting data .............................................................84

Lampiran 6.Hasil data statistik AUC ........................................................97

Lampiran 7.Hasil data statistik Cp Maks ..................................................101

Lampiran 8.Hasil data statistik AD ...........................................................105

Lampiran 9.T test hasil verifikasi kondisi uji..............................................109

Lampiran 10.Halaman Judul Ringkasan Tesis ............................................110

Lampiran 11.Halaman Judul Thesis Summary..............................................111

Lampiran 12.Halaman Judul Naskah Publikasi ...........................................112

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