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Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Self Nanoelmusifying Drug Delivery System of Rosuvastatin: Bioavailability Evaluation and In vitroIn vivo Correlation

Author(s): Nghia Thi Phan, Yen Thi Hai Tran, Linh Tran Nguyen, Yen Kieu Hoang, Cuong Khac Bui, Hoa Dang Nguyen and Giang Thi Thu Vu*

Volume 21, Issue 5, 2024

Published on: 30 December, 2022

Page: [734 - 743] Pages: 10

DOI: 10.2174/1567201820666221220104244

Price: $65


Background: Rosuvastatin, most commonly used in the form of calcium salt, belongs to the statin groups of synthetic antihyperlipidemic agents. Rosuvastatin possesses high permeability, however, its aqueous solubility is poor, causing a slow dissolution rate in water. Consequently, this dissolution rate has a decisive role in the release and absorption of rosuvastatin in the gastrointestinal tube.

Objective: The aims of this study were to evaluate the absorption of the drug from the self-nano emulsifying drug delivery system of rosuvastatin (Ros SNEDDS) compared to rosuvastatin substance and to develop a level-A in vitro-in vivo correlation (IVIVC) for Ros SNEDDS.

Methods: An in-house developed LC-MS/MS method was used to determine the concentrations of rosuvastatin in dog plasma. Six beagle dogs received an intravenous dose, Ros SNEDDS, rosuvastatin substance. In vitro dissolution of the Ros SNEDDS was carried out with different conditions. Correlation models were developed from the dissolution and absorption results of Ros SNEDDS.

Results: The results showed a 1.7-fold enhanced oral bioavailability and 2.1-time increase of rosuvastatin Cmax in Ros SNEDDS form, compared to the rosuvastatin substance. A 900 ml dissolution medium of pH of 6.6 has demonstrated its suitability, the in vitro dissolution model was studied and supported by the Weibull equation with a weighting factor of 1/y2 as it presented the lowest values of AIC.

Conclusion: Ros SNEDDS demonstrated higher bioavailability of rosuvastatin in comparison to rosuvastatin substance and established a level A IVIVC used in future bioequivalence trials.

Keywords: Absorption, deconvolution, dissolution, in vitro-in vivo correlation, pharmacokinetics, rosuvastatin.

Graphical Abstract
Li, Z.; Tian, S.; Gu, H.; Wu, Z.; Nyagblordzro, M.; Feng, G.; He, X. In vitro-in vivo predictive dissolution-permeation-absorption dynamics of highly permeable drug extended-release tablets via drug dissolution/absorption simulating system and pH alteration. AAPS PharmSciTech, 2018, 19(4), 1882-1893.
Administration, F.D. Guidance for industry: extended release oral dosage forms: development, evaluation, and application of in vitro/in vivo correlations. US Department of Health and Human Services, Center for Drug Evaluation and Research; CDER, 1997. Available from:
European Medicines Agency. Guideline on quality of oral modified release products; European Medicines Agency, 2014. Available from: 2014.
Sankalia, J.M.; Sankalia, M.G.; Mashru, R.C. Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: Establishment of level A IVIVC. J. Control. Release, 2008, 129(1), 49-58.
Sánchez-Dengra, B.; González-García, I.; González-Álvarez, M.; González-Álvarez, I.; Bermejo, M. Two-step in vitro-in vivo correlations: Deconvolution and convolution methods, which one gives the best predictability? Comparison with one-step approach. Eur. J. Pharm. Biopharm., 2021, 158, 185-197.
Abo Enin, H.A.; Abdel-Bar, H.M. Solid super saturated self-nanoemulsifying drug delivery system (sat-SNEDDS) as a promising alternative to conventional SNEDDS for improvement rosuvastatin calcium oral bioavailability. Expert Opin. Drug Deliv., 2016, 13(11), 1513-1521.
Luvai, A.; Mbagaya, W.; Hall, A.S.; Barth, J.H. Rosuvastatin: a review of the pharmacology and clinical effectiveness in cardiovascular disease. Clin. Med. Insights Cardiol., 2012, 6, CMC.S4324.
Salem, H.F.; Kharshoum, R.M.; Halawa, A.K.A.; Naguib, D.M. Preparation and optimization of tablets containing a self-nano-emulsifying drug delivery system loaded with rosuvastatin. J. Liposome Res., 2018, 28(2), 149-160.
Soran, H.; Durrington, P. Rosuvastatin: efficacy, safety and clinical effectiveness. Expert Opin. Pharmacother., 2008, 9(12), 2145-2160.
White, C.M. A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin. J. Clin. Pharmacol., 2002, 42(9), 963-970.
Inugala, S.; Eedara, B.B.; Sunkavalli, S.; Dhurke, R.; Kandadi, P.; Jukanti, R.; Bandari, S. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: in vitro and in vivo evaluation. Eur. J. Pharm. Sci., 2015, 74, 1-10.
Morakul, B. Self-nanoemulsifying drug delivery systems (SNEDDS): an advancement technology for oral drug delivery. Pharm. Sci. Asia, 2020, 47(3), 205-220.
Shukla, S.; Modi, D.; Shah, D. A review on solid self-nanoemulsifying drug delivery system: an approach for bioavailability enhancement. World J. Pharm. Pharm. Sci., 2016, 5(5), 302-316.
Vu, G.T.T.; Phan, N.T.; Nguyen, H.T.; Nguyen, H.C.; Tran, Y.T.H.; Pham, T.B.; Nguyen, L.T.; Nguyen, H.D. Application of the artificial neural network to optimize the formulation of self-nanoemulsifying drug delivery system containing rosuvastatin. J. Appl. Pharm. Sci., 2020, 10(9), 1-11.
Tang, X.; Tai, L.; Yang, X.; Chen, F.; Xu, H.; Pan, W. In vitro and in vivo evaluation of gliclazide push-pull osmotic pump coated with aqueous colloidal polymer dispersions. Drug Dev. Ind. Pharm., 2013, 39(1), 67-76.
Wang, H.; Cheng, L.; Wen, H.; Li, C.; Li, Y.; Zhang, X.; Wang, Y.; Wang, Y.; Wang, T.; Pan, W.; Yang, X. A time-adjustable pulsatile release system for ketoprofen: In vitro and in vivo investigation in a pharmacokinetic study and an IVIVC evaluation. Eur. J. Pharm. Biopharm., 2017, 119, 192-200.
Zhang, X.; Li, Q.; Ye, M.; Zhao, Z.; Sun, J.; Yang, X.; Pan, W. Preparation, characterization and in vitro/in vivo evaluation of oral time-controlled release etodolac pellets. AAPS PharmSciTech, 2018, 19(2), 610-620.
Veng-Pedersen, P. Noncompartmentally-based pharmacokinetic modeling. Adv. Drug Deliv. Rev., 2001, 48(2-3), 265-300.
Tang, M.; Hu, P.; Huang, S.; Zheng, Q.; Yu, H.; He, Y. Development of an extended-release formulation for apremilast and a level A in vitro-in vivo correlation study in beagle dogs. Chem. Pharm. Bull. (Tokyo), 2016, 64(11), 1607-1615.
Badadhe, G.S.; Dalavi, N. Review on self nano emulsifying drug delivery system. Sys Rev Pharm., 2022, 13(1), 63-68.
Cherniakov, I.; Domb, A.J.; Hoffman, A. Self-nano-emulsifying drug delivery systems: an update of the biopharmaceutical aspects. Expert Opin. Drug Deliv., 2015, 12(7), 1121-1133.
BASF. Safety Data Sheet, Cremophor® RH 40 Surfactant. 2012. Available from:
Rowe, R.C.; Sheskey, P.; Quinn, M. Handbook of Pharmaceutical Excipients, 6th ed; Pharmaceutical Press, 2009, pp. 542-548.
Nair, A.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm., 2016, 7(2), 27-31.
Crestor film-coated tablets, Summary of Product Characteristics. Available from:
Balakumar, K.; Raghavan, C.V. selvan, N.T.; prasad, R.H.; Abdu, S. Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf. B Biointerfaces, 2013, 112, 337-343.
Karasulu, H.Y.; Gundogdu, E.; Turk, U.O.; Turgay, T.; Apaydin, S.; Simsir, I.Y.; Yilmaz, C.; Karasulu, E. Enhancing solubility and bioavailability of rosuvastatin into self nanoemulsifying drug delivery system. Curr. Drug Deliv., 2018, 15(7), 1072-1082.
Nair, A.B.; Singh, B.; Shah, J.; Jacob, S.; Aldhubiab, B.; Sreeharsha, N.; Morsy, M.A.; Venugopala, K.N.; Attimarad, M.; Shinu, P. Formulation and evaluation of self-nanoemulsifying drug delivery system derived tablet containing sertraline. Pharmaceutics, 2022, 14(2), 336.
Kazi, M.; Al-Swairi, M.; Ahmad, A.; Raish, M.; Alanazi, F.K.; Badran, M.M.; Khan, A.A.; Alanazi, A.M.; Hussain, M.D. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: Preparation, in vitro and in vivo assessment. Front. Pharmacol., 2019, 10, 459.
Baloch, J.; Sohail, M.F.; Sarwar, H.S.; Kiani, M.H.; Khan, G.M.; Jahan, S.; Rafay, M.; Chaudhry, M.T.; Yasinzai, M.; Shahnaz, G. Self-nanoemulsifying drug delivery system (SNEDDS) for improved oral bioavailability of chlorpromazine: In vitro and in vivo evaluation. Medicina (Kaunas), 2019, 55(5), 210.
Ruiz Picazo, A.; Martinez-Martinez, M.T.; Colón-Useche, S.; Iriarte, R.; Sánchez-Dengra, B.; González-Álvarez, M.; García-Arieta, A.; González-Álvarez, I.; Bermejo, M. In vitro dissolution as a tool for formulation selection: Telmisartan two-step IVIVC. Mol. Pharm., 2018, 15(6), 2307-2315.
Koçak, E.; Çelebier, M. ALTINÖZ, S. Application of RP-HPLC for determination of the dissociation constants of rosuvastatin calcium. Hacettepe Univ. J. Facul. Pharm., 2012, (2), 133-144.
Borkar, N.; Xia, D.; Holm, R.; Gan, Y.; Müllertz, A.; Yang, M.; Mu, H. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium. Eur. J. Pharm. Sci., 2014, 51, 204-210.

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