Optimization of Naringenin Self-Nano Emulsifying Drug Delivery System (SNEDDS) Formula with D-optimal Mixture Design Method

Gendis Purno Yudanti; Ilham Kuncahyo; Endang Diyah Ikasari

doi:10.24071/jpsc.004319

Optimization of Naringenin Self-Nano Emulsifying Drug Delivery System (SNEDDS) Formula with D-optimal Mixture Design Method

Gendis Purno Yudanti, Ilham Kuncahyo, Endang Diyah Ikasari

Abstract

This study aimed to optimize and formulate the poorly water-soluble naringenin in the Self-Nano Emulsifying Drug Delivery System (SNEDDS) using D-optimal mixture design. D-optimal mixture design was used to optimize SNEDDS loading naringenin by selecting SNEDDS composition as an independent factor and SNEDDS characterization as a response. SNEDDS in the optimal formula were characterized, including transmittance, particle size, emulsification time, and drug loading. Triacetin, Tween 80, and transcutol p were respectively the selected oil, surfactant, and co-surfactant phases for their greatest ability to dissolve naringenin. The optimization results showed that the optimal formula was that using 10% triacetin, 70% of Tween 80, and 20% of transcutol p. SNEDDS loading naringenin produced nanoemulsion with 88.74±2.27 % of transmittance, 14.8 nm of particle size, 51.13 ± 4.53 mg/L of drug loading, and 18.58 ± 0.62 second of emulsification time. This study concludes that the D-optimal mixture design can be used to optimize and prepare the SNEDDS loading poorly-water soluble naringenin.

Keywords

Naringenin; SNEDDS; Triacetin; Transcutol p; Tween 80

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References

formula shows the optimum area which is shown in the grey area. This overlay plot is a combination of contour plots on four critical parameters, namely emulsification time, drug loading, the transmittance percentage and particle size. The red dot in one of the optimum areas is the optimum formula suggested by the Design Expert results from several predictions of the optimum formula in the optimum area, which can be seen in Figure 4.

CONCLUSIONS

Based on the research that was conducted, the following conclusions can be drawn: The optimal proportions of triacetin, tween 80 and transcutol P components in the manufacture of naringenin SNEDDS using the D – optimal mixture design method obtained a ratio of triacetin, tween 80, and transcutol P of 10.16 : 69.84 : 20. The results of testing the critical parameters on the optimum formula obtained the value of emulsification time 18.58 ± 0.62 seconds, drug loading 51.13 ± 4.53 mg/L, transmittance percentage 88.74% ± 2.275, and globule size 14.8 nm .

ACKNOWLEDGEMENTS

This research was funded by ITEKES Cendekia Utama Kudus.

REFERENCES

Abdul Sisak, M. A., Daik, R., & Ramli, S., 2017. Study on the effect of oil phase and co-surfactant on microemulsion systems. Malaysian Journal of Analytical Sciences, 21, 1409–1416.

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(3), 276–289.

Daga, A. S., Ingole, B. D., Kulkarni, S. S., & Biyani, K. R., 2012. Self emulsifying drug delivery system: Hitherto and novel approach. Research Journal of Pharmacy and Technology, 5(6), 736–745.

Hashem, F. M., Al-Sawahli, M. M., Nasr, M., & Ahmed, O. A. A., 2015. Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems – Enhancement of oral bioavailability. Drug Design, Development and Therapy, 9, 3141–3152.

Khan, A. W., Kotta, S., Ansari, S. H., Sharma, R. K., & Ali, J, 2015. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid naringenin: design, characterization, in vitro and in vivo evaluation. Drug Delivery, 22(4), 552–561.

Kumar, M., Bishnoi, R. S., Shukla, A. K., & Jain, C. P, 2019. Techniques for formulation of nanoemulsion drug delivery system: a review. Preventive Nutrition and Food Science, 24(3), 225–234.

Kuncahyo, I., Choiri, S., Fudholi, A., Martien, R., & Rohman, A, 2019. Assessment of fractional factorial design for the selection and screening of appropriate components of a self-nanoemulsifying drug delivery system formulation. Advanced Pharmaceutical Bulletin, 9(4), 609–618.

Kyatanwar, A. U., Jadhav, K. R., & Kadam, V. J, 2010. Available online through Self micro-emulsifying drug delivery system (SMEDDS): review. Journal of Pharmacy Research, 3(1), 75–83.

Leichner, C., Baus, R. A., Jelkmann, M., Plautz, M., Barthelmes, J., Dünnhaupt, S., & Bernkop-Schnürch, A, 2019. In vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for nasal administration of dimenhydrinate. Drug Delivery and Translational Research, 9(5), 945–955.

Nazzal, S., Smalyukh, I. I., Lavrentovich, O. D., & Khan, M. A. (2002). Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system (SNEDDS) of ubiquinone: mechanism and progress of emulsion formation. International Journal of Pharmaceutics, 235(1–2), 247–265.

Pratiwi, L., Fudholi, A., Martien, R., & Pramono, S, 2018. Uji stabilitas fisik dan kimia sediaan SNEDDS (Self-nanoemulsifying Drug Delivery System) dan nanoemulsi fraksi etil asetat kulit manggis (Garcinia mangostana L.). Traditional Medicine Journal, 23(2), 84–90.

Priani, S. E., Nurrayyan, N., & Darusman, F. (2017). Formulation self nano emulsifying drug delivery system glimepiride using oleic acid as oil phase. Pharmaciana, 7(2), 267.

Rebello, C. J., Beyl, R. A., Lertora, J. J. L., Greenway, F. L., Ravussin, E., Ribnicky, D. M., Poulev, A., Kennedy, B. J., Castro, H. F., Campagna, S. R., Coulter, A. A., & Redman, L. M, 2020. Safety and pharmacokinetics of naringenin: a randomized, controlled, single-ascending-dose clinical trial. Diabetes, Obesity and Metabolism, 22(1), 91–98.

Sari, A. ., & Herdiana, Y, 2016. Review: formulasi Nanoemulsi terhadap peningkatan kualitas obat. Farmaka, 16(1), 247–254.

Seema, G., & Kumar, S. A, 2014. Self nanoemulsifying drug delivery system: a noval approach for improving bioavailability. Journal of Drug Delivery and Therapeutics, 4(6), 33–38.

Syukri, Y., Nugroho, B. H., & Istanti, I, 2020. Penggunaan D-optimal mixture design untuk optimasi dan formulasi Self-Nano Emulsifying Drug Delivery System (SNEEDS) asam mefenamat. Jurnal Sains Farmasi & Klinis, 7(3), 180.

Winarti, L., Suwaldi, Martien, R., & Hakim, L, 2018. Formulation of insulin self nanoemulsifying drug delivery system and its in vitro-in vivo study. Indonesian Journal of Pharmacy, 29(3), 157–166.

Wolfe, D. T., Hermanson, D. R., Ii, B. A. B., Diri, A. K., Diri, P. K., Chotimah, C., Rohayati, S., М.А., Akademik, K., Pratama, R.Y.S., Educational Psychology Journal, 2(2), 65–72.

DOI: https://doi.org/10.24071/jpsc.004319