Optimization of self-nano emulsifying drug delivery system of rifampicin for nebulization using cinnamon oil as oil phase

Authors

  • I Komang Aan Adi Ricardo Sekolah Tinggi Farmasi Mahaganesha
  • Dewa Ayu Arimurni Sekolah Tinggi Farmasi Mahaganesha

DOI:

https://doi.org/10.12928/pharmaciana.v14i3.28892

Keywords:

SNEDDS, rifampicin, cinnamon oil, nebulizer, D-optimal mixture design

Abstract

Lung delivery can overcome the problems related to the effectiveness of tuberculosis treatment by increasing the drug concentration at the target site. Rifampicin as the first-line antibiotic for tuberculosis has low water solubility and is unstable in gastric which hinders its effectiveness. Self-nanoemulsifying drug delivery system (SNEDDS) is a strategy known to improve the solubility and stability of such drugs. This study aimed to obtain the optimum formula of rifampicin SNEDDS intended for lung nebulization using essential oil as an oil phase. Several essential oils are known to have effective antibacterial on Mycobacterium tuberculosis. However, a high capability to solubilize the drug is required for SNEDDS formulation. Cinnamon oil, tween 80, and transcutol P were chosen as SNEDDS components for optimization using a D-optimal mixture based on the physicochemical characteristics. The optimum formula comprised 12.65% cinnamon oil, 75.00% tween 80, and 12.35% transcutol P which dispersed easily to form a highly transparent emulsion in normal saline under 1 minute. Upon dilution with saline, the optimal SNEDDS can produce a homogenous nanometer droplet (169.2±19.771 nm, PDI of 0.258±0.070) with acceptable pH for lung administration. It also has a viscosity similar to water (0.94±0.01 cP) which allows it to be nebulized easily (aerosol output rate of 0.14±0.02 g/min). Although the diluted SNEDDS has a zeta potential of -2.533±0.268 mV, it was stable for up to 4 hours during the nebulization. These results indicate the potential of cinnamon oil-based rifampicin SNEDDS to be an alternative in the pulmonary delivery of rifampicin via nebulization.

References

Aisy, Z. H. R., Puspita, O. E., & Shalas, A. F. (2021). Optimasi Formula Nanoemulsi Nifedipin dengan Metode Self-Nanoemulsifying Drug Delivery System (SNEDDS). Pharmaceutical Journal of Indonesia, 6(2), 85–95.

Akbar, N. D., Nugroho, A. K., & Martono, S. (2022). Artikel Review: Optimasi Formulasi SNEDDS dengan Simplex Lattice Design dan Box Behnken Design. Jurnal Ilmiah Farmako Bahari, 13(1), 90–100.

American Association for Respiratory Care. (2023). Pulmonary Disease Aerosol Delivery Devices: A Guide for Physicians, Nurses, Pharmacists, and Other Health Care Professionals (4th ed.). American Association for Respiratory Care.

Andrade-Ochoa, S., Nevárez-Moorillón, G. V., Sánchez-Torres, L. E., Villanueva-García, M., Sánchez-Ramírez, B. E., Rodríguez-Valdez, L. M., & Rivera-Chavira, B. E. (2015). Quantitative Structure-Activity Relationship of Molecules Constituent of Different Essential Oils with Antimycobacterial Activity Against Mycobacterium tuberculosis and Mycobacterium bovis. BMC Complementary and Alternative Medicine, 15, 332.

Annisa, R., Mutiah, R., Yuwono, M., & Hendradi, E. (2023). The Development Formulation of Eleutherine palmifolia Extract-Loaded Self Nanoemulsifying Drug Delivery System (SNEDDS) Using D-Optimal Mixture Design Approach. International Journal of Applied Pharmaceutics, 15(5), 269–276.

Arbain, N. H., Basri, M., Salim, N., Wui, W. T., & Abdul Rahman, M. B. (2018). Development and Characterization of Aerosol Nanoemulsion System Encapsulating Low Water Soluble Quercetin for Lung Cancer Treatment. Materials Today: Proceedings, 5, S137–S142.

Astuti, I. Y., Marchaban, Martien, R., & Nugroho, A. E. (2017). Design and Optimization of Self Nano-Emulsifying Drug Delivery System Containing a New Anti-Inflammatory Agent Pentagamavunon-0. Indonesian Journal of Chemistry, 17(3), 365–375.

Avachat, A. M., & Patel, V. G. (2015). Self Nanoemulsifying Drug Delivery System of Stabilized Ellagic Acid–Phospholipid Complex with Improved Dissolution and Permeability. Saudi Pharmaceutical Journal, 23, 276–289.

Beandrade, M. U. (2018). Formulasi dan Karakterisasi SNEDDS Ekstrak Jinten Hitam (Nigella sativa) dengan Fase Minyak Ikan Hiu Cucut Botol (Centrophorus sp) serta Uji Aktivitas Imunostimulan. JPSCR: Journal of Pharmaceutical Science and Clinical Research, 3(1), 50–61.

Costa, A., Pinheiro, M., Magalhães, J., Ribeiro, R., Seabra, V., Reis, S., & Sarmento, B. (2016). The Formulation of Nanomedicines for Treating Tuberculosis. Advanced Drug Delivery Reviews, 102, 102–115.

Darusman, F., Dwiatama, A., & Priani, S. E. (2023). Formulasi dan Karakterisasi Self-Nanoemulsifying Drug Delivery System (SNEDDS) Esomeprazol Magnesium Trihidrat. Jurnal Sains Farmasi & Klinis, 10(1), 10–20.

Divate, M. P., Bawkar, S. U., Chakole, R. D., & Charde, M. S. (2021). Self Nano-Emulsifying Drug Delivery System: A Review. Journal of Advanced Scientific Research, 12(3 Suppl 2), 1–12.

Elbardisy, B., Boraie, N., & Galal, S. (2022). Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization. Pharmaceutics, 14(12). https://doi.org/10.3390/pharmaceutics14122717

Fithri, N. A., Mardiyanto, Novita, R. P., & Andrean, V. (2017). Furosemide Self Nano Emulsifying Drug Delivery System (SNEDDS) Formulation Comprising of Capryol-90, Polysorbate-80, and PEG-400 with Simplex-Lattice-Design. Science & Technology Indonesia, 2(4), 85–88.

Fitria, A., Hanifah, S., Chabib, L., Uno, A. M., Munawwarah, H., Atsil, N., Pohara, H. A., Weuanggi, D. A., & Syukri, Y. (2021). Design and Characterization of Propolis Extract Loaded Self-Nano Emulsifying Drug Delivery System as Immunostimulant. Saudi Pharmaceutical Journal, 29, 625–634.

Gautam, S., Qureshi, K. A., Jameel Pasha, S. B., Dhanasekaran, S., Aspatwar, A., Parkkila, S., Alanazi, S., Atiya, A., Khan, M. M. U., & Venugopal, D. (2023). Medicinal Plants as Therapeutic Alternatives to Combat Mycobacterium tuberculosis: A Comprehensive Review. Antibiotics, 12, 541.

Grotz, E., Tateosian, N. L., Salgueiro, J., Bernabeu, E., Gonzalez, L., Manca, M. L., Amiano, N., Valenti, D., Manconi, M., García, V., Moretton, M. A., & Chiappetta, D. A. (2019). Pulmonary Delivery of Rifampicin-Loaded Soluplus Micelles against Mycobacterium tuberculosis. Journal of Drug Delivery Science and Technology, 53, 101170.

Hailu, N., Postema, M., Krejcar, O., & Assefa, D. (2020). Nebulization Criteria and Quantification. Fluids, 5, 91.

Hajrin, W., Subaidah, W. A., & Juliantoni, Y. (2024). Formulasi dan Karakterisasi Nanoemulsi dari Ekstrak Biji Buah Makasar (Brucea javanica (L) Merr). Indonesian Journal of Pharmaceutical Science and Technology, 11(1), 117–125.

Katzung, B. G. (2018). Basic & Clinical Phamacology (14th ed.). McGraw-Hill Education.

Kementerian Kesehatan RI. (2020). Pedoman Nasional Pelayanan Kedokteran Tata Laksana Tuberkulosis. Kementerian Kesehatan RI.

Khadka, P., Dummer, J., Hill, P. C., Katare, R., & Das, S. C. (2023). A Review of Formulations and Preclinical Studies of Inhaled Rifampicin for its Clinical Translation. Drug Delivery and Translational Research, 13, 1246–1271.

Lu, Y., Qi, J., & Wu, W. (2018). Lipid Nanoparticles: In Vitro and In Vivo Approaches in Drug Delivery and Targeting. In A. M. Grumezescu (Ed.), Drug Targeting and Stimuli Sensitive Drug Delivery Systems (pp. 749–783). Elsevier.

Mantena, A. D., Dontamsetti, B. R., & Nerella, A. (2015). Formulation, Optimization and In Vitro Evaluation of Rifampicin Nanoemulsions. International Journal of Pharmaceutical Sciences and Drug Research, 7(6), 451–455.

Maretti, E., Rustichelli, C., Gualtieri, M. L., Costantino, L., Siligardi, C., Miselli, P., Buttini, F., Montecchi, M., Leo, E., Truzzi, E., & Iannuccelli, V. (2019). The Impact of Lipid Corona on Rifampicin Intramacrophagic Transport Using Inhaled Solid Lipid Nanoparticles Surface-Decorated with a Mannosylated Surfactant. Pharmaceutics, 11, 508.

Nuari, Y. R., Wahyuningsih, I., & Prabawati, S. (2021). Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Piroxicam: Evaluation on Anti-Inflammatory Activity in Wistar Rats. Pharmaciana, 11(2), 185–194.

Parikh, R., Patel, L., & Dalwadi, S. (2014). Microparticles of Rifampicin: Comparison of Pulmonary Route with Oral Route for Drug Uptake by Alveolar Macrophages, Phagocytosis Activity and Toxicity Study in Albino Rats. Drug Delivery, 21(6), 406–411.

Pratiwi, L., Fudholi, A., Martien, R., & Pramono, S. (2018). Physical and Chemical Stability Test of SNEDDS (Self-Nanoemulsifying Drug Delivery System) and Nanoemulsion Ethyl Acetate Fraction of Garcinia mangostana L. Majalah Obat Tradisional, 23(2), 84–90.

Priani, S. E., Nurrayyan, & Darusman, F. (2017). Formulation Self Nano Emulsifying Drug Delivery System Glimepiride Using Oleic Acid as Oil Phase. Pharmaciana, 7(2), 267–276.

Purnomo, H., & Syamsul, E. S. (2017). Statistika Farmasi (Aplikasi Praktis dengan SPSS). Grafika Indah.

Reddy, M. R., & Gubbiyappa, K. S. (2022). Formulation Development, Optimization and Characterization of Pemigatinib-Loaded Supersaturable Self-Nanoemulsifying Drug Delivery Systems. Future Journal of Pharmaceutical Sciences, 8, 45.

Rehman, F. U., Farid, A., Shah, S. U., Dar, M. J., Rehman, A. U., Ahmed, N., Rashid, S. A., Shaukat, I., Shah, M., Albadrani, G. M., Kamel, M., Altyar, A. E., Abdel-Daim, M. M., & Shah, K. U. (2022). Self-Emulsifying Drug Delivery Systems (SEDDS): Measuring Energy Dynamics to Determine Thermodynamic and Kinetic Stability. Pharmaceuticals, 15, 1064.

Sahumena, M. H., Suryani, & Rahmadani, N. (2019). Formulasi Self-Nanoemulsifiying Drug Delivery System (SNEDDS) Asam Mefenamat Menggunakan VCO dengan Kombinasi Surfaktan Tween dan Span. Journal Syifa Sciences and Clinical Research, 1(2), 37–46.

Sawicki, R., Golus, J., Przekora, A., Ludwiczuk, A., Sieniawska, E., & Ginalska, G. (2018). Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model. Molecules, 23, 2381.

Shah, K., Chan, L. W., & Wong, T. W. (2017). Critical Physicochemical and Biological Attributes of Nanoemulsions for Pulmonary Delivery of Rifampicin by Nebulization Technique in Tuberculosis Treatment. Drug Delivery, 24(1), 1631–1647.

Somasundaram, S., Ram, A., & Sankaranarayanan, L. (2014). Isoniazid and Rifampicin as Therapeutic Regimen in the Current Era: A Review. Journal of Tuberculosis Research, 2, 40–51.

Sopyan, I., Gozali, D., Sriwidodo, & Guntina, R. K. (2022). Design-Expert Software (DOE): An Application Tool for Optimization in Pharmaceutical Preparations Formulation. International Journal of Applied Pharmaceutics, 14(4), 55–63.

Suryani, Sahumena, M. H., Alfiandi, Putrawansya, L. R. P., Adjeng, A. N. T., Aswan, M., & Ruslin. (2019). The Self-Nanoemulsifying Drug Delivery System Formulation of Mefenamic Acid. Asian Journal of Pharmaceutics, 13(4), 287–294.

Syukri, Y., Fitria, A., Hanifah, S., & Idrati, M. (2021). Development of New Indonesian Propolis Extract-Loaded Self-Emulsifying: Characterization, Stability and Antibacterial Activity. Advanced Pharmaceutical Bulletin, 11(1), 120–129.

Syukri, Y., Nugroho, B. H., & Istanti. (2020). Penggunaan D-Optimal Mixture Design untuk Optimasi dan Formulasi Self-Nano Emulsifying Drug Delivery System (SNEDDS) Asam Mefenamat. Jurnal Sains Farmasi & Klinis, 7(3), 180–187.

Tsume, Y., Mudie, D. M., Langguth, P., Amidon, G. E., & Amidon, G. L. (2014). The Biopharmaceutics Classification System: Subclasses for In Vivo Predictive Dissolution (IPD) Methodology and IVIVC. European Journal of Pharmaceutical Sciences, 57, 152–163.

Vidya Raj, C. K., Venugopal, J., Muthaiah, M., Chadha, V. K., Brammacharry, U., Swappna, M., Sangeetha, A. V., Dhandapani, S. P., Kareedhi, V. R., Calivarathan, L., Karthick, M., & Jayapal, K. (2022). In-Vitro Anti-Mycobacterium tuberculosis Effect of Eugenol. Indian Journal of Tuberculosis, 69(4), 647–654.

Vu, H.-D., Vu, T.-H., Mai, N. L., Pande, D. C., Dao, D. V., Rehm, B. H. A., Nguyen, N.-T., Grant, G. D., Tran, C.-D., Zhu, Y., & Dau, V. T. (2024). In-Flight Electro-Neutralisation Electrospray for Pulmonary Drug Delivery. Nano Today, 55, 102217.

Wang, B., Wang, L., Yang, Q., Zhang, Y., Qinglai, T., Yang, X., Xiao, Z., Lei, L., & Li, S. (2024). Pulmonary Inhalation for Disease Treatment: Basic Research and Clinical Translations. Materials Today Bio, 25, 100966.

Winarti, L., Suwaldi, Martien, R., & Hakim, L. (2016). Formulation of Self-Nanoemulsifying Drug Delivery System of Bovine Serum Albumin Using HLB (Hydrophilic-Lypophilic Balance) Approach. Indonesian Journal of Pharmacy, 27(3), 117–127.

World Health Organization. (2023). Global Tuberculosis Report 2023. World Health Organization.

Yadav, P., Rastogi, V., & Verma, A. (2020). Application of Box–Behnken Design and Desirability Function in The Development and Optimization of Self-Nanoemulsifying Drug Delivery System for Enhanced Dissolution of Ezetimibe. Future Journal of Pharmaceutical Sciences, 6, 7.

Downloads

Published

2024-11-30

Issue

Section

Pharmaceutics and Pharmaceutical Technology