PENGEMBANGAN AMILUM SINGKONG (Manihot esculenta Crantz) FULLY GELATINIZED DALAM FORMULASI SEDIAAN NON-EFFERVESCENT FLOATING TABLETS VETERINER RANITIDIN HCl

I GUSTI NGURAH A D P, Dr. apt. T.N. Saifullah Sulaiman, M.Si.; Prof. Dr. apt. Abdul Rohman, M.Si.; Dr. drh. Retno Murwanti, M.P.

2021 | Disertasi | DOKTOR ILMU FARMASI

Penggalian potensi amilum singkong sebagai eksipien telah dilakukan dengan modifikasi polimer pada amilum singkong (Manihot esculenta Crantz). Penelitian ini bertujuan untuk mengembangkan eksipien baru untuk menghasilkan sediaan tablet non effervescent floating systems melalui modifikasi secara fisika (fully gelatinized) amilum singkong. Kondisi proses modifikasi terdiri atas suhu fully gelatinized cassava starch (FGCS), lama pemanasan, suhu oven dan lama oven. Analisis karakteristik sifat fisik meliputi morfologi granula amilum dengan mikroskop polarisasi cahaya dan Scanning Microscope Electron (SEM), profil Native Cassava Starch (NCS) dan Fully Gelatinized Cassava Starch (FGCS) dengan menggunakan Rapid Visco Analysis (RVA), analisis sifat kristanilitas cassava starch menggunakan X-ray Diffraction (XRD), makroskopik-mikroskopik, analisis perubahan daerah kristalin dan amorf menggunakan spektroskopi Fourier Transform Infrared (FTIR), Viskositas, Texture Profile Analyzer (TPA) dan analisis derajat retrogradasi menggunakan Differential Scanning Calorimetry (DSC). Metode formulasi tablet Non Effervescent Floating Tablets (NEFT) ranitidin HCl menggunakan metode granulasi. Metode granulasi dipilih karena semua bahan yang ada dalam formula berupa serbuk halus, sehingga tidak dapat langsung dikempa. Analisis data disolusi berbasis kompartemen dihitung dengan menggunakan software WinSAAM dan penetapan kadar ranitidin HCl untuk uji in vivo dilakukan dengan HPLC. Hasil modifikasi fisika (fully gelatinized) amilum singkong menunjukkan SEM FGCS Permukaan tampak seperti sponge dengan lubang yang lebih banyak dan memiliki diameter rata â�� rata lebih besar dari NCS (11,8-29,25 �µm), peningkatan daerah amorf pada FGCS (1,010) lebih tinggi dibandingkan dengan NCS (0,991) pada pengamatan dengan spektroskopi FTIR. Hasil analisis sifat termal polimer dengan DSC didapatkan hasil FGCS memiliki onset temperature (To) 102,09oC; entalpi transisi (��H) 4,32; derajat retrogradasi 143,4; dan glass transition (tg) FGCS tidak terlihat yang menunjukkan amilum sudah mengalami fully gelatinized secara total, pengamatan XRD menunjukkan proses fully gelatinized menyebabkan hilangnya puncak pada 2 teta 15o dan 23oC dan yang tersisa pada 2 teta 17o sehingga hasil modifikasi dengan FG mengubah kristalin tipe A menjadi tipe B. RVA yang menggambarkan sifat amilograf FGCS memiliki profil gelatinisasi amilum tipe A. Analisis tekstur dengan TPA didapatkan hasil FGCS memiliki nilai hardness, fracturability yang rendah dan springiness yang tinggi ini mengindikasikan semakin tingginya jumlah amilopektin pada FGCS. NEFT memiliki floating lag time rata-rata 15-30 menit. Dengan software WinSAAM, diperoleh hasil pelepasan ranitidin HCL dari sediaan NEFT mengikuti model tiga kompartemen. Dari penelitian ini, disimpulkan bahwa ranitidin HCl dapat diformulasikan menjadi sediaan gastroretentive dengan sistem non effervescent floating tablets menggunakan matrik FGCS. Kata Kunci: fully gelatinized, amilum, non effervescent, tablet, floating, WinSAAM

Potential exploration of cassava starch as an excipient has been carried out by modifying the polymer in cassava starch (Manihot esculenta Crantz). This research aims to develop new excipients to produce non-effervescent floating systems tablets through physical modification (fully gelatinized) cassava starch. Modification process conditions consist of fully gelatinized cassava starch (FGCS) temperature, heating time, oven temperature and oven duration. Analysis of physical characteristics including morphology of starch granules was carried out using a light polarization microscope and Scanning Microscope Electron (SEM), Native Cassava Starch (NCS) and Fully Gelatinized Cassava Starch (FGCS) profiles using Rapid Visco Analysis (RVA), analysis of cassava starch crystallinity using X- ray Diffraction (XRD), macroscopic-microscopy, analysis of changes in crystalline and amorphous regions using Fourier Transform Infrared (FTIR), Viscosity, Texture Profile Analyzer (TPA) and analysis of degree of retrogradeation using Differential Scanning Calorimetry (DSC). The Non Effervescent Floating Tablets (NEFT) ranitidine HCl tablet formulation method uses granulation method. The granulation method was chosen because all the ingredients in the formula are in the form of fine powder, so they cannot be directly compressed. Compartment-based dissolution data analysis was calculated using the WinSAAM software and HPLC system for determination of ranitidine HCl levels for in vivo testing. The result of physics modification (fully gelatinized) of cassava starch showed SEM FGCS The surface looks like a sponge with more holes and has an average diameter greater than NCS (11,8-29,25 �µm), Increased amorphous region in FGCS (1,010) higher than NCS (0,991) based on FTIR observation. The results of the analysis of the thermal properties of the polymer with DSC showed that the FGCS had an onset temperature (To) 102,09oC transition / ��H 4,32; degree of retrogradation 143,4; and glass transition (tg) FGCS is not visible which indicates that starch has fully gelatinized, XRD observations show fully gelatinized process causing loss of peak at 2 tides 15o and 23oC and remaining at 2 tides 17o so that the results of the modification with FG convert crystalline type A to type B. RVA illustrates the nature of the amylograph FGCS has a type A profile of starch gelatinization. Texture analysis with TPA shows that FGCS has a value of hardness, low fracturability and high springiness, indicating the higher amount of amylopectin in FGCS. NEFT has an average floating lag time of 15-30 minutes. Using WinSAAM software, the results of releasing ranitidine HCL from NEFT preparations follow the three compartment model. This study can be concluded that ranitidine HCl can be formulated into a gastroretentive preparation with a non-effervescent floating tablets system using the FGCS matrix. Keywords: fully gelatinized, starch, non effervescent, tablet, floating, WinSAAM

Kata Kunci : fully gelatinized, amilum, non effervescent, tablet, floating, WinSAAM