Optimization of Selfnanoemulsifying Drug Delivery System (SNEDDS) Formulation of Ethil Acetate Fraction Soursop Leaf as Antioxidant
Abstract
Soursop leaves have acetogenin compounds that can be used to fight cancer in the presence of adenosine triphosphate (ATP) inhibition. Acetogenin is a long-chain fatty acid derivative (C23 or C34) which is very difficult to dissolve in water so that it will cause low oral bioavailability. The use of Selfnanoemulsifying Drug Delivery System (SNEDDS) as a drug delivery system can increase bioavailability and increase the solubility of a drug. Optimization of the use of VCO as the oil phase, tween 80 as surfactant and propylene glycol as co-surfactant in the SNEDDS formula using the Simplex Lattice Design method. The responses used in the optimization are % transmittance and emulsification time. Verification of the optimal SNEDDS formula obtained with one sample t-test. The optimal formula of SNEDDS ethyl acetate fraction of soursop leaves was tested for particle size with Partcle Size Analyzer, zeta potential with zeta sizer and antioxidant activity using ABTS. The optimal formula was obtained at the concentration of the components of VCO oil (0.56 ml), Surfactant (3.50 ml), and Propylene glycol (0.93 ml) with a desirability value of 0.769. The results of the verification of the optimal formula show that there is no significant difference between the prediction and the actual, which means that the Simplex Lattice Design method is valid and can describe the % transmittance response and emulsification time of SNEDDS ethyl acetate fraction of soursop leaves. The optimal formula for SNEDDS has an emulsification time of 53±1.527 seconds, transmittance value of % 96.3±0.360%. The particle size results obtained from the optimal formula were 13.83 nm ± 0.650, the polydispersity index was 0.143 ± 0.128. The zeta potential test results obtained were -0.23 mV ± 0.057. The optimal formula for the ethyl acetate fraction of soursop leaf SNEDDS has a very strong antioxidant activity with an IC50 value of 16.89 ppm.
References
Agu K C and Okolie P N, 2017, Food. Sci. Nutr. 5 ,1029–36
Alwadei M, Kazi M, Alanazi FK. Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals - Curcumin and thymoquinone. Saudi Pharm J. 2019;27(6):866-6. https://doi.org/10.1016/j.jsps.2019.05.008.
Baloch J, Sohail MF, Sarwar HS, Kiani MH, Khan GM, Jahan S, Rafay M, Chaudhry MT, Yasinzai M, Shahnaz G. Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation. Medicina. 2019; 55(5):210. https://doi.org/10.3390/medicina55050210.
Diba, R.F., Yasni, S., Yuliani, S. 2014. Nanoemulsifikasi Spontan Ekstrak Jintan Hitam dan Karakteristik Produk Enkapsulasinya (Spontaneous Nanoemulsification of Black Cumin Extract and the Characteristics of Encapsulation Product), Jurnal Teknologi dan Industri Pangan, 25(2), 134.
Ermawati, D.E., Wulandari W, Yugatama A, 2020, Optimization Of Olive Oil, Tween 80, And Propylene Glycol Of Selfnanoemulsifying Drug Delivery System Of Zinc Oxide By D-Optimal Method, Jurnal Farmasi Sains Dan Komunitas, Volume 17, No 2, 92-101.
Ersita dan Kardewi, 2016, Uji Efektivitas Antibakteri Fraksi Aktif Daun Sirsak (Annonamuricata Linn) Terhadap Bakteri Escherichia Coli, Jurnal Kesehatan dan Kedokteran, Volume 3, No 2: 96-107.
Khoirunisa, M., 2019, Uji Aktivitas Antioksidan Self-Nanoemulsifying Drug Delivery System (SNEDDS) Ekstrak Biji Jinten Hitam (Nigella Sativa L.) Dengan Metode DPPH, Karya Tulis Ilmiah, Fakultas Kedokteran Universitas Islam Indonesia.
Kuentz, M., 2011. Oral self-emulsifying drug delivery systems, from biopharmaceutical to technical formulation aspects. Journal of Drug Delivery Science and Technology, 21: 17–26.
Marks, D.B., A.D. Marks &C.M. Smith., 2000, Biokimia Kedokteran Dasar Sebuah Pendekatan Klinis, Alih Bahasa Brahm U., Pendit. Jakarta: UGC.
Pham Huy, L.A., H. He., & C. Pham Huy., 2008, Free Radicals, Antioxidants in Disease and Helath, International Journal of Biomedical Science, 4 (2): 89-96.
Pouton, C.W. dan Porter, C.J.H., 2008. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Advanced Drug Delivery Reviews, 60: 625–637.
Pradana P.Y., Suratmo and Retnowati R., 2015, Isolasi dan Karakterisasi Senyawa Turunan Acetogenin dari Daun Sirsak (Annona muricata) Serta Uji Toksisitas, Kimia Student Journal, 1 (1), 798–804.
Rahmadhani, R.A., Riyadi, D. H. S., Triwibowo, Bayu., Kusumaningtyas R.D., 2017, Review Pemanfaatan Defign Expert untuk Optimasi Komposisi Campuran Minyak Nabati Sebagai Bahan Baku Sintetis Biodisel, Jurnal Teknik Kimia dan Llingkugan, 1 (1), 11-16.
Rao, S.V.R., Agarwal, P., dan Shao, J., 2008a. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs. International Journal of Pharmaceutics, 362: 10–15.
Rao, S.V.R., Yajurvedi, K., dan Shao, J., 2008b. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of protein drugs: III. In vivo oral absorption study. International Journal of Pharmaceutics, 362: 16–19.
Sulkhan, A A R, Artanti, A N, Ermawati, D E, Prihapsara, F, 2018, Optimization of Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Annona muricata L. leaves chloroform extract using VCO (Virgin Coconut Oil) as an oil phase, IOP Conf. Series: Materials Science and Engineering 578 (2019) 012046, doi:10.1088/1757-899X/578/1/012046.
Surbakti dan Nadiya, 2019, Uji Mutu Ekstrak Daun Sirsak (Annona muricata Linn.) Yang Di Ekstraksi Secara Maserasi Dengan Pelarut Etanol 70%, Jurnal Farmasi, Vol 1 No 1.
Widyaningrum, Herlina. 2012. Sirsak Si Buah Ajaib 10.000x Lebih Hebat dari Kemoterapi. Yogyakarta: MedPress.
Yang C, Gundala S R, Mukkavilli R, Vangala S, Reid M D and Aneja R, 2015, Carcinogenesis, 36, 656–659.
