DAFTAR ISI
HALAMAN JUDUL .....................................................................................
i
HALAMAN PENGESAHAN .......................................................................
ii
SURAT PERNYATAAN ..............................................................................
iii
MOTTO DAN PERSEMBAHAN .................................................................
iv
KATA PENGANTAR ...................................................................................
v
DAFTAR ISI .................................................................................................. vii DAFTAR TABEL ..........................................................................................
x
DAFTAR GAMBAR .....................................................................................
xi
DAFTAR LAMPIRAN .................................................................................. xii INTISARI ...................................................................................................... xiii ABSTRACT ..................................................................................................... xiv BAB I. PENDAHULUAN ............................................................................
1
A. Latar Belakang ..............................................................................
1
B. Rumusan Masalah .........................................................................
2
C. Tujuan Penelitian ...........................................................................
2
D. Manfaat Penelitian .........................................................................
3
E. Tinjauan Pustaka ...........................................................................
3
1. Fenofibrat dan asam fenofibrat .................................................
3
2. Dispersi padat ...........................................................................
4
3. Kelarutan...................................................................................
8
4. Disolusi ..................................................................................... 10
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5. Spektrofotometri ....................................................................... 12 6. Monografi Bahan ...................................................................... 15 F. Landasan Teori .............................................................................. 17 G. Hipotesis ........................................................................................ 17 BAB II. METODE PENELITIAN.............................................................. 18 A. Bahan dan Alat .............................................................................. 18 1. Bahan ........................................................................................ 18 2. Alat ........................................................................................... 18 B. Jalannya Penelitian ........................................................................ 18 1. Pembuatan dapar fosfat pH 6,8 ................................................. 18 2. Pembuatan larutan stok ............................................................ 19 3. Penentuan panjang gelombang maksimum .............................. 19 4. Pembuatan kurva baku asam fenofibrat .................................... 19 5. Pembuatan dispersi padat asam fenofibrat ............................... 20 6. Uji perolehan kembali dispersi padat asam fenofibrat ............. 21 7. Uji kelarutan dispersi padat asam fenofibrat ............................ 21 8. Uji disolusi dispersi padat asam fenofibrat ............................... 22 C. Analisis Data ................................................................................. 22 D. Skema Jalannya Penelitian ............................................................ 23 BAB III. HASIL PENELITIAN DAN PEMBAHASAN .......................... 24 A. Panjang Gelombang Maksimal Asam Fenofibrat ......................... 24 B. Kurva Baku Asam Fenofibrat........................................................ 24 C. Organoleptis Dispersi Padat Asam Fenofibrat .............................. 26
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D. Perolehan Kembali ........................................................................ 27 E. Kelarutan Dispersi Padat Asam Fenofibrat ................................... 27 F. Disolusi Dispersi Padat Asam Fenofibrat ..................................... 28 BAB IV. KESIMPULAN DAN SARAN .................................................... 31 A. Kesimpulan .................................................................................... 31 B. Saran .............................................................................................. 31 DAFTAR PUSTAKA ................................................................................... 32 DAFTAR LAMPIRAN ................................................................................ 34
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DAFTAR TABEL
Tabel I.
Sifat Fisikokimia Fenofibrat dan Asam Fenofibrat ....................
4
Tabel II.
Istilah Perkiraan Kelarutan .........................................................
9
Tabel III.
Formula Standar Tablet Asam Fenofibrat .................................. 20
Tabel IV.
Formula Dispersi Padat Asam Fenofibrat .................................. 20
Tabel V.
Hasil Pengukuran Absorbansi Kurva Baku Asam Fenofibrat dengan Spektrofotometer UV pada λ maksimal 298,7 nm......... 25
Tabel VI.
Data Hasil Uji Organoleptis Dispersi Padat Asam Fenofibrat ... 26
Tabel VII. Hasil Uji Perolehan Kembali Dispersi Padat Asam Fenofibrat.. 27 Tabel VIII. Hasil Uji Kelarutan Dispersi Padat Asam Fenofibrat................. 27 Tabel IX.
Harga DE 60 (%) Dispersi Padat Asam Fenofibrat dengan Penambahan SLS dan SSG .. ..................................................... . 29
x
DAFTAR GAMBAR
Gambar 1. Struktur kimia a) fenofibrat; b) asam fenofibrat ..........................
3
Gambar 2. Struktur kimia sodium starch glikolat .......................................... 16 Gambar 3. Struktur kimia sodium lauril sulfat .............................................. 17 Gambar 4. Skema jalannya penelitian pengaruh inkorporasi sodium lauril sulfat dan sodium starch glikolat terhadap kelarutan dan disolusi asam fenofibrat dalam sistem dispersi padat .............................. 23 Gambar 5. Hasil pengukuran panjang gelombang maksimal asam fenofibrat pada spektrofotometer UV ........................................................... 24 Gambar 6. Grafik kurva baku asam fenofibrat dalam dapar fosfat pH 6,8 pada spektrofotometer UV dengan λ maksimal 298,7 nm ........... 25 Gambar 7. Hasil dispersi padat asam fenofibrat a.metode1; b. metode 2; c. metode 3 .................................................................................. 26 Gambar 8. Profil disolusi asam fenofibrat dan metode inkorporasi dispersi padat asam fenofibrat.. ................................................................. 29
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DAFTAR LAMPIRAN
Lampiran 1. Certificate of Analysis Asam Fenofibrat ................................. 34 Lampiran 2. Certificate of Analysis Sodium Starch Glikolat ...................... 35 Lampiran 3. Penentuan Panjang Gelombang Maksimal .............................. 36 Lampiran 4. Kurva Baku Asam Fenofibrat .................................................. 37 Lampiran 5. Data Perolehan Kembali .......................................................... 38 Lampiran 6. Organoleptis Dispersi Padat Asam Fenofibrat ........................ 40 Lampiran 7. Data Kelarutan ......................................................................... 41 Lampiran 8. Hasil Disolusi .......................................................................... 42 Lampiran 9. Contoh Perhitungan DE 60 ..................................................... 46 Lampiran 10. Hasil Statistik Anova Uji Kelarutan ........................................ 49 Lampiran 11. Hasil Statistik Uji Disolusi ...................................................... 50 Lampiran 12. Surat Keterangan Telah Melakukan Penelitian di Laboratorium Farmasetika Fakultas Farmasi Universitas Wahid Hasyim Semarang ....................................................... 51
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INTISARI
Asam fenofibrat adalah obat penurun kadar lipid yang tidak larut dalam air dan termasuk dalam kategori Biopharmaceutical Classification System (BCS) II, sehingga diperlukan upaya untuk meningkatkan kelarutan dan disolusi agar tercapai ketersediaan hayati yang lebih baik. Penelitian ini bertujuan untuk mengetahui pengaruh inkorporasi surfaktan sodium lauril sulfat (SLS) dan superdisintegran sodium starch glikolat (SSG) terhadap kelarutan dan disolusi asam fenofibrat dalam sistem dispersi padat Inkorporasi SLS dan SSG dengan asam fenofibrat dalam dispersi padat dilakukan menggunakan 3 cara berbeda, kemudian hasilnya diuji kelarutan dan disolusi dalam medium dapar fosfat pH 6,8. Data yang diperoleh dianalisis menggunakan uji statistik Anova satu jalan dengan taraf kepercayaan 95%. Hasil penelitian menunjukkan inkorporasi SLS dan SSG tidak meningkatkan kelarutan, namun meningkatkan disolusi asam fenofibrat. Perbedaan metode inkorporasi tidak memberikan perbedaan disolusi asam fenofibrat. Kata kunci: Dispersi padat, Asam fenofibrat, Kelarutan, disolusi
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ABSTRACT Fenofibric acid is lipid lowering drug that insoluble in water and included in category of Biopharmaceutical Classification System (BCS) II, so that necessary to improve the solubility and dissolution in order to achieve a better bioavailability. This study aims to determine the influence of incorporation of surfactant sodium lauryl sulfate (SLS) and superdisintegrant sodium starch glycolate (SSG) on the solubility and dissolution of fenofibric acid in solid dispersion system. Incorporation of SLS and SSG with fenofibric acid in solid dispersion made using 3 different methods. Then the results are tested solubility and dissolution in medium buffer phosphate pH 6.8. Data were analyzed using one way Anova with a 95% confidence level. The results showed that incorporation of SLS and SSG couldn’t increase the solubility but could increase the dissolution of fenofibric acid. Differences methods of incorporation didn’t provide the increase in dissolution of fenofibric acid. Keyword: Solid Dipersion, Fenofibric Acid, Solubility, Disolution
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