OPTIMASI FORMULA SNEDDS RIFAMPICIN PADA Mycobacterium tuberculosis: STUDI IN VITRO

Yudhytha Anggarhani Quraisyin, Dr.rer.nat. Ronny Martien, M.Si.; dr. Antonia Morita Iswari Saktiawati., Ph.D

2024 | Tesis | S2 Bioteknologi

Indonesia menempati posisi kedua tertinggi di dunia untuk kasus tuberkulosis (TB), dengan peningkatan jumlah pasien yang signifikan akibat pandemi Covid-19. Sebanyak 41% pasien TB, terutama yang resisten terhadap terapi lini pertama seperti rifampicin, tidak dapat diobati secara efektif karena terbatasnya pilihan obat TB yang nyaman dan efektif. Penelitian ini bertujuan untuk mengembangkan sistem penghantaran rifampicin melalui SNEDDS. Formula optimum SNEDDS Rifampicin didapatkan dengan optimasi menggunakan D-optimal Design Expert 13, dengan konsentrasi Miglyol 812N, Tween 80 dan PEG 400 sebagai variabel bebas serta waktu emulsifikasi, ukuran dan distribusi droplet sebagai respon yang diamati. Dari optimasi didapatkan formula optimum SNEDDS Rifampicin yang dapat teremulsifikasi secara spontan, serta memiliki kejernihan seperti air. Hasil uji distribusi, ukuran dan potensial zeta droplet menggunakan Particle Size Analysis (PSA) juga menunjukkan karakteristik SNEDDS yang baik dan stabil. Hasil ini dikonfirmasi dengan pengujian morfologi menggunakan TEM yang menunjukkan droplet berbentuk spherical serta berukuran <100nm>

Indonesia ranks second highest in the world for tuberculosis (TB) cases, with a significant increase in the number of patients due to the Covid-19 pandemic. Approximately 41% of TB patients, particularly those resistant to first-line therapies such as rifampicin, cannot be effectively treated due to the limited availability of convenient and effective TB drug options. This study aims to develop a rifampicin delivery system using Self-Nanoemulsifying Drug Delivery Systems (SNEDDS). The optimal SNEDDS rifampicin formula was obtained through optimization using a D-optimal Design Expert 13, with concentrations of Miglyol 812N, Tween 80, and PEG 400 as independent variables, and emulsification time, droplet size, and distribution as observed responses. The optimal SNEDDS rifampicin formula could spontaneously emulsify, producing an isotropic nanoemulsion with water-like clarity. The results of the distribution, size, and zeta potential of the droplets using Particle Size Analysis (PSA) also indicated good and stable SNEDDS characteristics. These findings were confirmed by morphological testing using Transmission Electron Microscopy (TEM), which showed spherical droplets with sizes less than 100 nm. Drug loading tests using UV-Vis spectrophotometry yielded a recovery percentage of 81.143% ± 0.01, supported by a lower Minimum Inhibitory Concentration (MIC) compared to pure rifampicin and rifampicin tablets. Stability studies, including thermodynamic stability and short-term storage, demonstrated that SNEDDS rifampicin remained stable under various stress conditions. This study indicates that the developed SNEDDS system can enhance rifampicin delivery and may serve as a superior alternative to current oral delivery systems.

Kata Kunci : Mycobacterium spesies, formulasi SNEDDS, Rifampicin, nanoemulsi, TB