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Current Drug Delivery

Editor-in-Chief

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

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Research Article

In-Vitro and In-Vivo Evaluation of Supersaturable Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Dutasteride

Author(s): Poonguzhali Subramanian, P. S. Rajnikanth*, Manish Kumar and Kumarappan Chidambram

Volume 17, Issue 1, 2020

Page: [74 - 86] Pages: 13

DOI: 10.2174/1567201816666191112111610

Price: $65

Abstract

Objective: A novel, Supersaturable Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) has been prepared to improve the Dutasteride's poor aqueous solubility.

Methods: By adding Hydroxy Propyl Methyl Cellulose (HPMC) as a precipitation inhibitor to conventional SNEDDS, a supersaturable system was prepared. Firstly, the prepared SNEDDS played an important role in increasing the aqueous solubility and hence oral absorption due to nano-range size. Secondly, the S-SNEDDS found to be advantageous over SNEDDS for having a higher drug load and inhibition of dilution precipitation of Dutasteride. Formulated S-SNEDDS (F1-F9) ranged from 37.42 ± 1.02 to 68.92 ± 0.09 nm with PDI 0.219-0.34 and drug loading of over 95 percent.

Results: The study of in-vitro dissolution revealed higher dissolution for S-SNEDDS compared to SNEDDS and Avodart soft gelatin capsule as a commercial product. In addition, higher absorption was observed for S-SNEDDS showing approximately 1.28 and 1.27 fold AUC (0-24h) and Cmax compared to commercial products. Therefore, S-SNEDDS has proven as a novel drug delivery system with a higher drug load, higher self-emulsification efficiency, higher stability, higher dissolution and pronounced absorption.

Conclusion: In conclusion, S-SNEDDS could be a newly emerging approach to enhance aqueous solubility in many folds for drugs belonging to BCS Class II and IV and thus absorption and oral bioavailability.

Keywords: Supersaturated Self-Nanoemulsifying Drug Delivery (S-SNEDDS), Hydroxy Propyl Methyl Cellulose (HPMC), Dutasteride, higher self-emulsification efficiency, Poor Aqueous Solubility, Nano-emulsion.

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[1]
Li, L.; Zhou, C.H.; Xu, Z.P. Self-Nanoemulsifying Drug-Delivery System and Solidified Self-Nanoemulsifying Drug-Delivery System. In: Nanocarriers for Drug Delivery; Elsevier, 2019; pp. 421-449.
[2]
Lee, D.H.; Yeom, D.W.; Song, Y.S.; Cho, H.R.; Choi, Y.S.; Kang, M.J.; Choi, Y.W. Improved oral absorption of dutasteride via Soluplus®-based supersaturable self-emulsifying drug delivery system (S-SEDDS). Int. J. Pharm., 2015, 478(1), 341-347.
[http://dx.doi.org/10.1016/j.ijpharm.2014.11.060] [PMID: 25437113]
[3]
AboulFotouh. K.; Allam, A.A.; El-Badry, M.; El-Sayed, A.M. Development and in vitro/in vivo performance of self-nanoemulsifying drug delivery systems loaded with candesartan cilexetil. Eur. J. Pharm. Sci., 2017, 109, 503-513.
[http://dx.doi.org/10.1016/j.ejps.2017.09.001] [PMID: 28889028]
[4]
Tran, T.H.; Guo, Y.; Song, D.; Bruno, R.S.; Lu, X. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. J. Pharm. Sci., 2014, 103(3), 840-852.
[http://dx.doi.org/10.1002/jps.23858] [PMID: 24464737]
[5]
Dash, R.N.; Mohammed, H.; Humaira, T.; Reddy, A.V. Solid supersaturatable self-nanoemulsifying drug delivery systems for improved dissolution, absorption and pharmacodynamic effects of glipizide. J. Drug Deliv. Sci. Technol., 2015, 28, 28-36.
[http://dx.doi.org/10.1016/j.jddst.2015.05.004]
[6]
Elkasabgy, N.A. Ocular supersaturated self-nanoemulsifying drug delivery systems (S-SNEDDS) to enhance econazole nitrate bioavailability. Int. J. Pharm., 2014, 460(1-2), 33-44.
[http://dx.doi.org/10.1016/j.ijpharm.2013.10.044] [PMID: 24184217]
[7]
Thomas, N.; Holm, R.; Müllertz, A.; Rades, T. In vitro and in vivo performance of novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS). J. Control. Release, 2012, 160(1), 25-32.
[http://dx.doi.org/10.1016/j.jconrel.2012.02.027] [PMID: 22405903]
[8]
Tung, N.T.; Tran, C.S.; Nguyen, H.A.; Nguyen, T.D.; Chi, S.C.; Pham, D.V.; Bui, Q.D.; Ho, X.H. Formulation and biopharmaceutical evaluation of supersaturatable self-nanoemulsifying drug delivery systems containing silymarin. Int. J. Pharm., 2019, 555, 63-76.
[http://dx.doi.org/10.1016/j.ijpharm.2018.11.036] [PMID: 30448315]
[9]
Chen, Y.; Chen, C.; Zheng, J.; Chen, Z.; Shi, Q.; Liu, H. Development of a solid supersaturatable self-emulsifying drug delivery system of docetaxel with improved dissolution and bioavailability. Biol. Pharm. Bull., 2011, 34(2), 278-286.
[http://dx.doi.org/10.1248/bpb.34.278] [PMID: 21415541]
[10]
Mahmoud, H.; Al-Suwayeh, S.; Elkadi, S. Design and optimization of self-nanoemulsifying drug delivery systems of simvastatin aiming dissolution enhancement. Afr. J. Pharm. Pharmacol., 2013, 7(22), 1482-1500.
[http://dx.doi.org/10.5897/AJPP2013.2987]
[11]
Baek, I.H.; Ha, E.S.; Yoo, J.W.; Jung, Y.; Kim, M.S. Design of a gelatin microparticle-containing self-microemulsifying formulation for enhanced oral bioavailability of dutasteride. Drug Des. Devel. Ther., 2015, 9, 3231-3238.
[PMID: 26150696]
[12]
Reddy, M.S.; Sowjanya, N. Formulation and in-vitro characterization of solid self-nanoemulsifying drug delivery system (s-SNEDDS) of simvastatin. J. Pharm. Sci. Res., 2015, 7(1), 40.
[13]
Tarkase, K.N.; Damale, P.S.; Kapare, P.S.; Lagad, V.A. Formulation and evaluation of supersaturable self nano-emulsifying drug delivery system of poorly water soluble atorvastatin calcium. Asian J. Pharm. Res. Develop, 2014, 22-23.
[14]
Rajinikanth, P.S.; Keat, N.W.; Garg, S. Self-nanoemulsifying drug delivery systems of Valsartan: Preparation and in-vitro characterization. Int. J. Drug Deliv., 2012, 4(2), 53.
[15]
Dutasteride; U.S. Food and Drug Administration, U.S. Department of Health and Human Services, 2015. [ONLINE] Available at: http://www.accessdata.fda.gov/scripts/cder/dissolution/dsp_SearchResults.cfm [Accessed 15 November 2015]
[16]
Krstić, M.; Popović, M.; Dobričić, V.; Ibrić, S. Influence of solid drug delivery system formulation on poorly water-soluble drug dissolution and permeability. Molecules, 2015, 20(8), 14684-14698.
[http://dx.doi.org/10.3390/molecules200814684] [PMID: 26287134]
[17]
Parasuraman, S.; Raveendran, R.; Kesavan, R. Blood sample collection in small laboratory animals. J. Pharmacol. Pharmacother., 2010, 1(2), 87-93.
[http://dx.doi.org/10.4103/0976-500X.72350] [PMID: 21350616]
[18]
Lee, D.H.; Yeom, D.W.; Song, Y.S.; Cho, H.R.; Choi, Y.S.; Kang, M.J.; Choi, Y.W. Improved oral absorption of dutasteride via Soluplus®-based supersaturable self-emulsifying drug delivery system (S-SEDDS). Int. J. Pharm., 2015, 478(1), 341-347.
[http://dx.doi.org/10.1016/j.ijpharm.2014.11.060] [PMID: 25437113]
[19]
Kang, M.J.; Cho, H.R.; Lee, D.H.; Yeom, D.W.; Choi, Y.W.; Choi, Y.S. A Method to monitor dutasteride in rat plasma using liquid-liquid extraction and multiple reaction monitoring: Comparisons and validation. Mass Spectrometry Lett., 2014, 5(3), 79-83.
[http://dx.doi.org/10.5478/MSL.2014.5.3.79]
[20]
Kim, M.S.; Ha, E.S.; Choo, G.H.; Baek, I.H. Preparation and in vivo evaluation of a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system. Int. J. Mol. Sci., 2015, 16(5), 10821-10833.
[http://dx.doi.org/10.3390/ijms160510821] [PMID: 25984604]
[21]
Beg, S.; Katare, O.P.; Saini, S.; Garg, B.; Khurana, R.K.; Singh, B. Solid self-nanoemulsifying systems of olmesartan medoxomil: Formulation development, micromeritic characterization, in vitro and in vivo evaluation. Powder Technol., 2016, 294, 93-104.
[http://dx.doi.org/10.1016/j.powtec.2016.02.023]
[22]
Gao, P.; Guyton, M.E.; Huang, T.; Bauer, J.M.; Stefanski, K.J.; Lu, Q. Enhanced oral bioavailability of a poorly water soluble drug PNU-91325 by supersaturatable formulations. Drug Dev. Ind. Pharm., 2004, 30(2), 221-229.
[http://dx.doi.org/10.1081/DDC-120028718] [PMID: 15089057]
[23]
Warren, D.B.; Benameur, H.; Porter, C.J.; Pouton, C.W. Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: A mechanistic basis for utility. J. Drug Target., 2010, 18(10), 704-731.
[http://dx.doi.org/10.3109/1061186X.2010.525652] [PMID: 20973755]
[24]
Vadher, A.H.; Parikh, J.R.; Parikh, R.H.; Solanki, A.B. Preparation and characterization of co-grinded mixtures of aceclofenac and neusilin US2 for dissolution enhancement of aceclofenac. AAPS PharmSciTech, 2009, 10(2), 606-614.
[http://dx.doi.org/10.1208/s12249-009-9221-6] [PMID: 19444620]
[25]
Khan, F.; Islam, M.S.; Roni, M.A.; Jalil, R.U. Systematic development of self-emulsifying drug delivery systems of atorvastatin with improved bioavailability potential. Sci. Pharm., 2012, 80(4), 1027-1043.
[http://dx.doi.org/10.3797/scipharm.1201-06] [PMID: 23264948]

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