Nurfitri, Febri Hasanah (2025) Pembuatan dan Karakterisasi Komposit Obat Proton Pump Inhibitor (Lansoprazole) dengan Binder Berbasis Pati Resisten Tipe III dari Pati Singkong dengan Metode Wet Granulation. Masters thesis, Institut Teknologi Sepuluh Nopember.
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Abstract
Pati singkong merupakan salah satu attractive biopolymer terbaru yang digunakan dalam industry farmasi, salah satunya dalam pembuatan tablet. Pati singkong dapat dimodifikasi menjadi resistant starch tipe-3 (RS-3) dengan proses retrogradasi sehingga menghasilkan pati yang tahan panas, degradasi asam, dan degradasi enzim. Proton pump inhibitor (PPI) adalah golongan obat lepas lambat yang bekerja langsung pada sel-sel lambung untuk menurunkan produksi asam berlebih. Lansoprazole merupakan salah satu golongan obat PPI yang mempunyai paruh waktu di plasma pendek (1-2 jam) sehingga cocok dibuat sediaan lepas lambat. Bahan aktif PPI akan cepat larut dalam kondisi asam tinggi sehingga dibutuhkan adanya eksipien untuk melindungi inti obat dari kondisi keasaman lambung yang tinggi. Berdasarkan sifatnya yang tahan asam, penggunaan RS-3 dari pati singkong sebagai binder (eksipien) dalam pembuatan komposit obat PPI diharapkan dapat memberikan efek lepas lambat dengan dosis bertahap untuk mencapai efek terapi yang lebih lama dan mengurangi efek samping karena fluktuasi kadar obat dalam plasma. Pada penelitian ini, metode granulasi basah digunakan untuk mencampurkan komponen tablet secara homogen dan mencegah segregasi selama pencampuran. Penelitian ini bertujuan untuk mengetahui pengaruh penambahan binder RS-3 terhadap persentase pelepasan obat PPI. Secara sistematis pembuatan komposit obat PPI dengan binder RS-3 dimulai dengan membuat binder RS-3 dari campuran pati singkong dan air menggunakan proses high shear mixing (HSM) pada suhu 95⁰C. Hasil dari proses HSM didinginkan dalam freezer pada suhu -15⁰C selama 24 jam untuk melalui proses retrogradasi. Hasil produk retrogradasi dikeringkan dengan metode freeze dry. Produk kering dianalisa dengan Total Dietary Fiber (TDF). Tahap selanjutnya adalah membuat granul dan tablet komposit obat PPI dengan metode granulasi basah. Pada tahap ini dimulai dengan membuat mucilage RS-3 dengan melarutkan 1.5 g RS-3 menggunakan 2 ml akuades dan ditambahkan akuades panas hingga mencapai 10 ml. Kemudian mencampurkan mucilage pada konsentrasi 5%, 10%, 15%, 20% dan 25% dengan 0.3 g bahan aktif lansoprazole hingga terbentuk granul. Kemudian granul dicetak menggunakan alat press tablet dengan diameter 6-mm. Produk yang diperoleh dianalisa dengan Disolusi secara in vitro, SEM-EDX, FTIR dan DSC. Hasil penelitian menunjukkan bahwa penambahan binder RS-3 pada komposit obat PPI terbukti dapat mengontrol pelepasan jumlah obat terlarut dalam media asam dan memenuhi standar Farmakope Indonesia. Persentase jumlah obat terlarut terbaik dengan nilai terendah 0,42% diperoleh pada variabel penambahan binder RS-3 dengan pretreatment HSM 15 menit pada konsentrasi 25%. Berdasarkan analisa FTIR dan DSC juga diketahui bahwa penambahan binder RS-3 tidak menimbulkan reaksi kimia pada komposit obat sehingga tidak mengganggu stabilitas bahan aktif obat lansoprazole. Berdasarkan analisa SEM-EDX diketahui bahwa unsur khas lansoprazole yaitu S=O terdistribusi secara merata dengan persentase rata-rata 13-21%. Sehingga penggunaan RS-3 sebagai binder untuk mengontrol pelepasan obat dapat direkomendasi dan memberikan dukungan dalam pengembangan formulasi pengobatan.
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Starch is one of the newest attractive biopolymers used in the manufacture of tablets. Compared to other types of starch, starch produced from cassava contains a low amount of amylose, this makes cassava starch has benefits including low gelatinization temperature and low retrogradation rates, making it a preferable excipient for pharmaceutical applications. It can be modified into resistant starch type 3 (RS-3). Proton pump inhibitors (PPIs) represent a class of drugs which suppress gastric acid secretion. Lansoprazole is one of PPIs drug that has a short plasma half-life (1-2 hours), that make it compatible to be slow-release tablets. PPIs active ingredient (API) will dissolve quickly in highly acidic conditions. To protect the API from degradation, the tablet must be protected with excipient. The RS-3 used as a binder to produce proton pump inhibitor drug because of its acid and enzyme resistance. RS-3 as a binder is expected to provide a slow-release effect with gradual doses to achieve a longer therapeutic effect and reduce adverse effects due to fluctuations in drug levels in plasma. Wet granulation method was used to homogenize the PPIs composite components and avoid the segregation during mixing process. This research aims to determine the effects of adding RS-3 as a binder on the percentage of drug release. Systematically this research method starts with RS-3 production from cassava starch and aquadest uses high shear mixing (HSM) on 95⁰C. high amylose suspense resulting from this process will be cooled at -15⁰C on 24 hours for the retrogradation process. The retrogradation product results were dried using the freeze-dry method and analyzed by Total Dietary Fiber (TDF). The next step is to make PPIs drug composite granules and tablets using the wet granulation method. Mucilage from a 1.5-gram sample of the RS3 powder was dissolved in 2 ml of distilled water and boiled water was added while stirring to make up to 10 ml. Granules were formed by wet massing a 0.3-gram sample of lansoprazole powder with a binder concentration at 5%, 10%, 15%, 20% and 25% based on volume of the RS3 mucilage (w/v). Then the granules were pressed using 6-mm tablet press machine. The punch and die surfaces were lubricated with a 1% dispersion of magnesium stearate in chloroform to prevent sticking and allow easy ejection of the tablets
from the die. The product that has been obtained is then analysed by in vitro Dissolution test, SEM-EDX, FTIR and DSC. As a result, the addition of RS-3 binder on the PPIs drug composite was proven to be able to control the drug release in highly acid media and occupy the standards of the Indonesian Pharmacopoeia. Among the various formulations, F2e containing 25% binder RS-3 with pretreatment HSM 15 minutes were optimized based on the better drug release within 1 hours with percentage of drug release 0.42%. FTIR and DSC studies revealed compatibility of drug with excipients. Obtained SEM-EDX mapping of tablets showed that the typical element of lansoprazole S=O evenly distributed at contretations of 13-21%.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | Starch-based Pharmaceutical Excipient, Binder, Proton Pump Inhibitor, Resistant Starch, Slow-release Drug Load. |
| Subjects: | R Medicine > RS Pharmacy and materia medica T Technology > TP Chemical technology > TP156.C64 Controlled release technology |
| Divisions: | Faculty of Industrial Technology and Systems Engineering (INDSYS) > Chemical Engineering > 24101-(S2) Master Thesis |
| Depositing User: | Febri Hasanah Nurfitri |
| Date Deposited: | 04 Feb 2025 06:35 |
| Last Modified: | 04 Feb 2025 06:35 |
| URI: | http://repository.its.ac.id/id/eprint/118117 |
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