Optimization of Self-nanoemulsifying Drug Delivery System for Pterostilbene


Oktavia Eka Puspita(1*), Suwaldi Suwaldi(2), Akhmad Kharis Nugroho(3)

(1) Universitas Brawijaya
(2) Universitas Gadjah Mada
(3) Universitas Gadjah Mada
(*) Corresponding Author


Solubility is prerequisite for drug absorption across absorptive cell lining the small intestine. It is a problem for poor water soluble drug because limiting its bioavailability when administered by oral route. Lipid based delivery system such as self-nanoemulsifying delivery system (SNEDDS) can be utilized in improving its solubility so that better bioavailability is achieved. Pterostilbene has extremely low solubility in water then become its limiting factor for the bioavailability. This research developed SNEDDS for oral delivery of pterostilbene. Optimum composition of SNEDDS formulation was judged by its dispersion efficiency and clarity when dispersed in water. The efficiency of this formula in enhancing bioavailability was assessed by in vitro digestion model to predict its bioavailability by determining its bioaccessibility. The result showed that optimum composition of SNEDDS was achieved by soybean oil-Croduret® 50-Span 80-PEG 400 in ratio of 16.37 %, 32.07 %, 11.56 %, and 40 %, respectively. This formula has bioacessibility of 91.48 ± 2.18 %, and it is much higher compared to pterostilbene that was not formulated into SNEDDS, i.e 4.63 ± 1.11 %. Determined by dynamic light scattering, this optimum formula has droplet size of 31.8 nm when dispersed in water.

Full Text:



Agubata, C.O., Nzekwe, I.T., Obitte, N.C., Ugwu, C.E., Attama, A.A., Onunkwo, G.C., 2014. Effect of Oil, Surfactant and Co-Surfactant Concentrations on the Phase Behavior, Physicochemical Properties and Drug Release from Self-Emulsifying Drug Delivery Systems. J. Drug Discov. Dev. Deliv. 1, 1–7.

Ahmed, K., Li, Y., McClements, D.J., Xiao, H., 2012. Nanoemulsion- and emulsion-based delivery systems for curcumin: Encapsulation and release properties. Food Chem. 132, 799–807.

Amidon, G.L., Lennernäs, H., Shah, V.P., Crison, J.R., 1995. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability. Pharm. Res. 12, 413–420.

Basalious, E.B., Shawky, N., Badr-Eldin, S.M., 2010. SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: development and optimization. Int. J. Pharm. 391, 203–211.

Bethune, S.J., Schultheiss, N., Henck, J.-O., 2011. Improving the Poor Aqueous Solubility of Nutraceutical Compound Pterostilbene through Cocrystal Formation. Cryst. Growth Des. 11, 2817–2823.

Choo, Q.-Y., Yeo, S.C.M., Ho, P.C., Tanaka, Y., Lin, H.-S., 2014. Pterostilbene surpassed resveratrol for anti-inflammatory application: Potency consideration and pharmacokinetics perspective. J. Funct. Foods 11, 352–362.

Cuiné, J.F., McEvoy, C.L., Charman, W.N., Pouton, C.W., Edwards, G.A., Benameur, H., Porter, C.J.H., 2008. Evaluation of the impact of surfactant digestion on the bioavailability of danazol after oral administration of lipidic self-emulsifying formulations to dogs. J. Pharm. Sci. 97, 995–1012.

Dahan, A., Hoffman, A., 2008. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs. J. Control. Release Off. J. Control. Release Soc. 129, 1–10.

Fatouros, D.G., Mullertz, A., 2008. In vitro lipid digestion models in design of drug delivery systems for enhancing oral bioavailability. Expert Opin. Drug Metab. Toxicol. 4, 65–76.

Hauss, D.J., Fogal, S.E., Ficorilli, J.V., Price, C.A., Roy, T., Jayaraj, A.A., Keirns, J.J., 1998. Lipid-based delivery systems for improving the bioavailability and lymphatic transport of a poorly water-soluble LTB4 inhibitor. J. Pharm. Sci. 87, 164–169.

Huang, Y.-B., Tsai, Y.-H., Yang, W.-C., Chang, J.-S., Wu, P.-C., Takayama, K., 2004. Once-daily propranolol extended-release tablet dosage form: formulation design and in vitro/in vivo investigation. Eur. J. Pharm. Biopharm. 58, 607–614.

Kommuru, T.R., Gurley, B., Khan, M.A., Reddy, I.K., 2001. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int. J. Pharm. 212, 233–246.

Manickam, M., Ramanathan, M., Jahromi, M.A., Chansouria, J.P., Ray, A.B., 1997. Antihyperglycemic activity of phenolics from Pterocarpus marsupium. J. Nat. Prod. 60, 609–610.

Müllertz, A., Ogbonna, A., Ren, S., Rades, T., 2010. New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs. J. Pharm. Pharmacol. 62, 1622–1636.

Neslihan Gursoy, R., Benita, S., 2004. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacother. 58, 173–182.

Park, E.-S., Lim, Y., Hong, J.-T., Yoo, H.-S., Lee, C.-K., Pyo, M.-Y., Yun, Y.-P., 2010. Pterostilbene, a natural dimethylated analog of resveratrol, inhibits rat aortic vascular smooth muscle cell proliferation by blocking Akt-dependent pathway.

Vascul. Pharmacol. 53, 61–67.

Porter, C.J.H., Pouton, C.W., Cuine, J.F., Charman, W.N., 2008. Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv. Drug Deliv. Rev. 60, 673–691.

Pouton, C.W., 2000. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and “self-microemulsifying” drug delivery systems. Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 11 Suppl 2, S93-98.

Pouton, C.W., Porter, C.J.H., 2008. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Adv. Drug Deliv. Rev., Lipid-Based Systems for the Enhanced Delivery of Poorly Water Soluble Drugs 60, 625–637.

Qian, C., Decker, E.A., Xiao, H., McClements, D.J., 2012. Nanoemulsion delivery systems: influence of carrier oil on β-carotene bioaccessibility. Food Chem. 135, 1440–1447.

Rao, J., Decker, E.A., Xiao, H., McClements, D.J., 2013. Nutraceutical nanoemulsions: influence of carrier oil composition (digestible versus indigestible oil) on β-carotene bioavailability. J. Sci. Food Agric. 93, 3175–3183.

Riche, D., 2013. Effect of Pterostilbene on Cholesterol, Blood Pressure and Oxidative Stress (Clinical Trial Phase 3 No. NCT01267227). University of Mississippi Medical Center.

Sun, Y., Xia, Z., Zheng, J., Qiu, P., Zhang, L., McClements, D.J., Xiao, H., 2015. Nanoemulsion-based delivery systems for nutraceuticals: Influence of carrier oil type on bioavailability of pterostilbene. J. Funct. Foods 13, 61–70.

Yang, Y., McClements, D.J., 2013. Vitamin E bioaccessibility: influence of carrier oil type on digestion and release of emulsified α-tocopherol acetate. Food Chem. 141, 473–481.

Yeo, S.C.M., Ho, P.C., Lin, H.-S., 2013. Pharmacokinetics of pterostilbene in Sprague-Dawley rats: the impacts of aqueous solubility, fasting, dose escalation, and dosing route on bioavailability. Mol. Nutr. Food Res. 57, 1015–1025.

DOI: https://doi.org/10.14499/jfps

Article Metrics

Abstract views : 3107 | views : 2190


  • There are currently no refbacks.

Journal of Food and Pharmaceutical Sciences (ISSN: 2339-0948) -  Universitas Gadjah Mada, Indonesia.