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Pharmaceutical Nanotechnology

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ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

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Research Article

Self Nanoemulsifying Drug Delivery System of Sorafenib Tosylate: Development and In Vivo Studies

Author(s): Pamu Sandhya*, Pamu Poornima and Darna V.R.N. Bhikshapathi

Volume 8, Issue 6, 2020

Page: [471 - 484] Pages: 14

DOI: 10.2174/2211738508666201016151406

Price: $65

Abstract

Background: Sorafenib tosylate (SFN) belongs to the BCS class II drug with low solubility and undergoes first-pass metabolism, which leads to reduced bioavailability of 38%.

Objective: The present study aimed at developing SFN SNEDDS to improve their solubility and bioavailability.

Methods: Preliminary solubility studies were performed to identify oil, surfactant, and co-surfactant ratios. Pseudo tertiary phase diagram was constructed to select the areas of nanoemulsion based on the monophasic region. A total of 15 formulations of SFN SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. These SNEDDS further characterized for % transmission, content of the drug, and in vitro dissolution analysis. The optimized formulation was analyzed for particle size, Z average, entrapment efficiency, and SEM analysis.

Results: Based on the pseudo tertiary phase diagram, acrysol EL 135, kolliphor, and transcutol-P as oil, surfactant, and co-surfactant were selected, respectively. All the formulations were stable with no phase separation and maximum % transmittance of 98.92%. The formulation F15 was selected as an optimized one, based on maximum drug content of 99.89%, with 98.94% drug release within 1 hour and it will be stable for 6 months. From in vivo bioavailability studies, the Cmax of optimized SNEDDS (94.12±2.12ng/ml) is higher than pure SFN suspension (15.32±1.46 ng/ml) and the AUC0-∞ of optimized SNEDDS is also increased by 5 times (512.1±8.54 ng.h/ml) than pure drug (98.75±6.45ng.h/ml), which indicates improved bioavailability of the formulation.

Conclusion: SFN loaded SNEDDS could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first-pass metabolism and increased solubility.

Lay Summary: Renal cell carcinoma accounts for 2% of global cancer diagnoses and deaths, it has more than doubled in incidence in the developed world over the past half-century, and today is the ninth most common neoplasm in the United States. Sorafenib is a protein kinase inhibitor indicated as a treatment for advanced renal cell carcinoma. The present study aimed at developing Sorafenib SNEDDS to improve their solubility and bioavailability. A total of 15 formulations of Sorafenib SNEDDS were prepared and screened for phase separation and temperature variation using thermodynamic stability studies. Sorafenib loaded SNEDDS could potentially be exploited as a delivery system for increased oral bioavailability by 5 times when comparing with pure drug by minimizing first-pass metabolism and increased solubility.

Keywords: Bioavailability studies, pseudoternary phase diagram, SNEDDS, solubility, sorafenib tosylate, acrysol EL 135.

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[1]
Escudier B, Eisen T, Stadler WM, et al. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 2009; 27(20): 3312-8.
[http://dx.doi.org/10.1200/JCO.2008.19.5511] [PMID: 19451442]
[2]
Grignani G, Palmerini E, Dileo P, et al. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. Ann Oncol 2012; 23(2): 508-16.
[http://dx.doi.org/10.1093/annonc/mdr151] [PMID: 21527590]
[3]
Llovet JM, Ricci S, Mazzaferro V, et al. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359(4): 378-90.
[http://dx.doi.org/10.1056/NEJMoa0708857] [PMID: 18650514]
[4]
Maki RG, D’Adamo DR, Keohan ML, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol 2009; 27(19): 3133-40.
[http://dx.doi.org/10.1200/JCO.2008.20.4495] [PMID: 19451436]
[5]
Mori S, Cortes J, Kantarjian H, Zhang W, Andreef M, Ravandi F. Potential role of sorafenib in the treatment of acute myeloid leukemia. Leuk Lymphoma 2008; 49(12): 2246-55.
[http://dx.doi.org/10.1080/10428190802510349] [PMID: 19052971]
[6]
Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 2008; 7(10): 3129-40.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0013] [PMID: 18852116]
[7]
Widemann BC, Kim A, Fox E, et al. A phase I trial and pharmacokinetic study of sorafenib in children with refractory solid tumors or leukemias: a Children’s Oncology Group Phase I Consortium report. Clin Cancer Res 2012; 18(21): 6011-22.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3284] [PMID: 22962440]
[8]
Patel J, Kevin G, Patel A, Raval M, Sheth N. Design and development of a self-nanoemulsifying drug delivery system for telmisartan for oral drug delivery. Int J Pharm Investig 2011; 1(2): 112-8.
[http://dx.doi.org/10.4103/2230-973X.82431] [PMID: 23071930]
[9]
Sermkaew N, Ketjinda W, Boonme P. Phadoongsom but N, Wiwattanapatapee R. Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from crude extract of Andrographispaniculata. Eur J Pharm Sci 2013; 50(3-4): 459-66.
[http://dx.doi.org/10.1016/j.ejps.2013.08.006] [PMID: 23973887]
[10]
Kaur G, Chandel P, Harikumar SL. Formulation development of self-nanoemulsifying drug delivery system (SNEDDS) of celecoxib for improvement of oral bioavailability. Pharmacophore 2013; 4(4): 120-33.
[11]
Gupta S. Self-nanoemulsifying drug delivery system for adefovir, dipivoxil: design, characterization, in vitro and ex vivo evaluation. J Colloids Surf 2011; 392: 145-55.
[http://dx.doi.org/10.1016/j.colsurfa.2011.09.048]
[12]
Aparna C. Formulation and evaluation of solid self-emulsifying drug delivery system of ranolazine. J Glob Trends Pharm Sci 2014; 5(4): 2238-47.
[13]
Patel PV, Patel HK, Panchal SS, Mehta TA. Self micro-emulsifying drug delivery system of tacrolimus: formulation, in vitro evaluation and stability studies. Int J Pharm Investig 2013; 3(2): 95-104.
[http://dx.doi.org/10.4103/2230-973X.114899] [PMID: 24015381]
[14]
Aruna K. Geeta Al, Harikumar S. Formulation and evaluation of nanosuspension and nanoemulsion of rosuvastatin and their comparative study. Asian J Biochem Pharm Res 2015; 1(5): 101-16.
[15]
Nicolas C, Kenneth C. Ofokansi, Franklin C Kenechukwu. Development and evaluation of novel self-nanoemulsifying drug delivery systems based on a homolipid from Capra hircusand its psdeseed mixtures with melon oil for the delivery of indomethacin. Int J Pharm 2014; 2014: 1-9.
[16]
Date AA, Nagarsenker MS. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int J Pharm 2007; 329(1-2): 166-72.
[http://dx.doi.org/10.1016/j.ijpharm.2006.08.038] [PMID: 17010543]
[17]
Gang R, Si-Shen F. Preparation and characterization of poly (lactic acid)-poly (ethylene glycol) microspheres for controlled release of microspheres. Biomaterials 2003; 24: 5037-44.
[http://dx.doi.org/10.1016/S0142-9612(03)00419-8] [PMID: 14559017]
[18]
Ke Z, Hou X, Jia XB. Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D. Drug Des Devel Ther 2016; 10: 2049-60.
[http://dx.doi.org/10.2147/DDDT.S106356] [PMID: 27418807]
[19]
Lalit Kumar T, Mohan Lal K. Stability study and in vivo Evaluation of lornoxicam loaded ethyl cellulose microspheres. Int J Pharm Sci Drug Res 2014; 6(1): 26-30.
[20]
Zhang J, Peng Q, Shi S, et al. Preparation, characterization, and in vivo evaluation of a self-nanoemulsifying drug delivery system (SNEDDS) loaded with morin-phospholipid complex. Int J Nanomedicine 2011; 6: 3405-14.
[PMID: 22267925]
[21]
Khan IZ. Hussan M. A simple, rapid and sensitive RP-HPLC-UV method for the simultaneous determination of sorafenib & paclitaxel in plasma and pharmaceutical dosage forms: application to pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 2016; 1033-4: 261-70.

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