Login Register Cart 0
Generic placeholder image

Pharmaceutical Nanotechnology

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Self-microemulsifying Drug Delivery System for Solubility and Bioavailability Enhancement of Eprosartan Mesylate: Preparation, In-vitro, and In-vivo Evaluation

Author(s): Mukesh Subhash Patil* and Atul Arunrao Shirkhedkar

Volume 11, Issue 1, 2023

Published on: 09 December, 2022

Page: [56 - 69] Pages: 14

DOI: 10.2174/2211738510666220915100150

Price: $65

Abstract

Background: Formulations of eprosartan mesylate with a surfactant, like Kolliphor HS 15, an oil phase like Labrafil M 1944 CS, and a cosurfactant Transcutol HP by employing a liquid self-microemulsifying drug delivery system (SMEDDS) after screening several vehicles have been studied.

Objective: This study aimed to prepare a liquid self-microemulsifying drug delivery system for increasing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate.

Methods: The micro-emulsion unit, achieved through the phase diagram and augmented with the central-composite design (CCD) surface response process, was adjusted into SMEDDS by lyophilization using sucrose as a cryoprotective agent. Particle size, self-emulsification time, polydispersion index (PDI), zeta potential, differential scanning calorimeter (DSC) screening, in-vitro drug release, and in-vivo pharmacokinetics were the essential features of the formulations. The subsequent DSC experimentation indicated that the drug was integrated into S-SMEDDS. Eprosartan mesylate loaded SMEDDS formulation showed greater in-vitro and in-vivo drug release than conventional solid doses.

Results: SMEDDS has reported effectiveness in reducing the impact of pH of eprosartan mesylate, thereby improving its release efficiency. The HPLC method was successfully implemented to assess eprosartan mesylate concentration in Wister rat plasma after oral administration of commercial tablet EM, SMEDDS, and eprosartan mesylate. The pharmacokinetics parameters for rats were Cmax 1064.91 ± 225 and 1856.22 ± 749 ngmL-1, Tmax 1.9 ± 0.3 hr, and 1.2 ± 0.4 hr and AUC0~t were 5314.36 ± 322.61 and 7760.09 ± 249 ng/ml hr for marketed tablets and prepared SSMEDDS, respectively. When determined by AUC0~1, the relative bioavailability of eprosartan mesylate S-SMEDDC was 152.09 ± 14.33%.

Conclusion: The present study reports the formulation of a self-microemulsifying drug delivery system for enhancing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate in an appropriate solid dosage form.

Keywords: Surface Response System, EprosartanMesylate, Low Solubility, Pharmacokinetics, SMEDDS, Bioavailability

« Previous Next »
Graphical Abstract

[1]
Lemke TL, Williams DA. Foye’s Principles of Medicinal Chemistry. (6th ed.), Philadelphia: Lippincott Williams & Wilkins 2012.
[2]
Plosker GL. Eprosartan. Drugs 2009; 69(17): 2477-99.
[http://dx.doi.org/10.2165/11203980-000000000-00000] [PMID: 19911859]
[3]
Dangre P, Sawale V, Meshram S, Gunde M. Development and validation of RP-HPLC method for the simultaneous estimation of eprosartanmesylate and chlorthalidone in tablet dosage form. Int J Pharm Tech Res 2015; 8(2): 16-38.
[4]
Patil SS, Misra RDK. The significance of macromolecular architecture in governing structure-property relationship for biomaterial applications: An overview. Mater Technol 2018; 33(5): 364-86.
[http://dx.doi.org/10.1080/10667857.2018.1447266]
[5]
Sica DA. Clinical pharmacology of the angiotensin receptor antagonists. J Clin Hypertens 2001; 3(1): 45-9.
[http://dx.doi.org/10.1111/j.1524-6175.2001.00832.x] [PMID: 11416682]
[6]
Robins GW, Scott LJ. Eprosartan. Drugs 2005; 65(16): 2355-77.
[http://dx.doi.org/10.2165/00003495-200565160-00012] [PMID: 16266204]
[7]
Vishal P, Jadhav KS, Giri MA, Kendre P, Vibhute S, Borawake DD. Design and development of paliperidonemesoporous silica template as a platform for surge dose drug delivery system. Mater Technol 2019; 34: 117-25.
[8]
Nazzal S, Khan MA. Controlled release of a self-emulsifying formulation from a tablet dosage form: Stability assessment and optimization of some processing parameters. Int J Pharm 2006; 315(1-2): 110-21.
[http://dx.doi.org/10.1016/j.ijpharm.2006.02.019] [PMID: 16563673]
[9]
Choudhary A, Rana AC, Aggarwal G, Kumar V, Zakir F. Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability. Acta Pharm Sin B 2012; 2(4): 421-8.
[http://dx.doi.org/10.1016/j.apsb.2012.05.002]
[10]
Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000; 50(1): 47-60.
[http://dx.doi.org/10.1016/S0939-6411(00)00076-X] [PMID: 10840192]
[11]
Jang DJ, Jeong EJ, Lee HM, Kim BC, Lim SJ, Kim CK. Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion. Eur J Pharm Sci 2006; 28(5): 405-11.
[http://dx.doi.org/10.1016/j.ejps.2006.04.013] [PMID: 16777390]
[12]
Chen Y, Lu Y, Chen J, et al. Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt. Int J Pharm 2009; 376(1-2): 153-60.
[http://dx.doi.org/10.1016/j.ijpharm.2009.04.022] [PMID: 19394416]
[13]
Zhou S, Shang Q, Wang N, Li Q, Song A, Luan Y. Rational design of a minimalist nanoplatform to maximize immunotherapeutic efficacy: Four birds with one stone. J Control Release 2020; 328: 617-30.
[http://dx.doi.org/10.1016/j.jconrel.2020.09.035] [PMID: 32976902]
[14]
Li Q, Zhou Y, He W, et al. Platelet-armored nanoplatform to harmonize janus-faced IFN-γ against tumor recurrence and metastasis. J Control Release 2021; 338: 33-45.
[http://dx.doi.org/10.1016/j.jconrel.2021.08.020] [PMID: 34391837]
[15]
Jiang S, Li M, Haller A, et al. Encapsulation of polyprodrugs enables an efficient and controlled release of dexamethasone. Nanoscale Horiz 2022; 7: 198-210.
[16]
Misra RDK. Core–shell magnetic nanoparticle carrier for targeted drug delivery: Challenges and design. Mater Technol 2013; 118-26.
[17]
Attama AA, Nzekwe IT, Nnamani PO, Adikwu MU, Onugu CO. The use of solid self-emulsifying systems in the delivery of diclofenac. Int J Pharm 2003; 262(1-2): 23-8.
[http://dx.doi.org/10.1016/S0378-5173(03)00315-6] [PMID: 12927384]
[18]
Balakrishnan P, Lee BJ, Oh DH, et al. Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm 2009; 374(1-2): 66-72.
[http://dx.doi.org/10.1016/j.ijpharm.2009.03.008] [PMID: 19446761]
[19]
Cui S, Nie S, Li L, Wang C, Pan W, Sun J. Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine. Drug Dev Ind Pharm 2009; 35(5): 603-11.
[http://dx.doi.org/10.1080/03639040802488089] [PMID: 19040178]
[20]
Woo JS, Song YK, Hong JY, Lim SJ, Kim CK. Reduced food-effect and enhanced bioavailability of a self-microemulsifying formulation of itraconazole in healthy volunteers. Eur J Pharm Sci 2008; 33(2): 159-65.
[http://dx.doi.org/10.1016/j.ejps.2007.11.001] [PMID: 18178070]
[21]
Sachan R, Khatri K, Kasture SB. Self-emulsifying drug deliverysystem a novel approach for enhancement of bioavailability. Int J Pharm Tech Res 2010; 2: 1738-45.
[22]
Patel D, Sawant KK. Oral bioavailability enhancement of acyclovir by self-microemulsifying drug delivery systems (SMEDDS). Drug Dev Ind Pharm 2007; 33(12): 1318-1326, 18-26.
[http://dx.doi.org/10.1080/03639040701385527] [PMID: 18097805]
[23]
Shweta G, Sandip C, Krutika KS. Self-nanoemulsifying drug delivery system for adefovirdipivoxil: Design, characterization,in vitro and ex vivo evaluation. Colloids Surf A Physicochem Eng Asp 2011; 392: 45-55.
[24]
Li F, Song S, Guo Y, et al. Preparation and pharmacokinetics evaluation of oral selfemulsifying system for poorly water-soluble drug Lornoxicam. Drug Deliv 2015; 22(4): 487-98.
[http://dx.doi.org/10.3109/10717544.2014.885615] [PMID: 24524289]
[25]
Gershanik T, Benzeno S, Benita S. Interaction of a self-emulsifying lipid drug delivery system with the everted rat intestinal mucosa as a function of droplet size and surface charge. Pharm Res 1998; 15(6): 863-9.
[http://dx.doi.org/10.1023/A:1011968313933] [PMID: 9647351]
[26]
Prajapati BG, Patel M. Conventional and alternative methods to improve oral bioavailability of lipophilic drugs. Asian J Pharm 2007; 1: 1-8.
[27]
Patil PH, Mahajan HS. Mixed micelles for bioavailability enhancement of nelfinavir mesylate: In vitro characterisation and In vivo pharmacokinetic study. Mater Technol 2018; 33(12): 793-802.
[http://dx.doi.org/10.1080/10667857.2018.1511317]
[28]
Patil TS, Deshpande AS. Design, development, and characterisation of clofazimine-loaded mannosylated nanostructured lipid carriers: 33-Box-Behnken design approach. Mater Technol 2021; 36(8): 460-75.
[http://dx.doi.org/10.1080/10667857.2020.1774227]
[29]
Wei Y, Ye X, Shang X, et al. Enhanced oral bioavailability of silybin by a supersaturatable self-emulsifying drug delivery system (S-SEDDS). Colloids Surf A Physicochem Eng Asp 2012; 396: 22-8.
[http://dx.doi.org/10.1016/j.colsurfa.2011.12.025]
[30]
Patel MJ, Patel SS, Patel NM. A self-microemulsifying drug delivery system. Int J Pharm Res 2010; 4: 29-35.
[31]
Patil S, Gattani SG, Nirbhavane P, Katare OP, Patil K. Quality by Design (QbD) driven systematic development of nano-lipoidal carrier of poorly water soluble anti-tubercular agent-rifabutin. Mater Technol 2021; 37(8): 695-705.
[32]
Seo SW, Han HK, Chun MK, Choi HK. Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier. Int J Pharm 2012; 424(1-2): 18-25.
[http://dx.doi.org/10.1016/j.ijpharm.2011.12.051] [PMID: 22226878]
[33]
Pardeshi CV, Dhangar RN, Jagatap VR, Sonawane RO. New cationic neuronanoemulsion-laden Eulophiaherbaceamucilage based mucoadhesive hydrogel for intranasal delivery of chlorpromazine. Mater Technol 2021; 36(4): 189-202.
[http://dx.doi.org/10.1080/10667857.2020.1740859]
[34]
Craing DQM, Lievens HSR, Pitt KG. An investigation intothephysico- chemical properties of self- emulsifying measurements and particle size analysis. Int J Pharm 1993; 96: 147-55.
[http://dx.doi.org/10.1016/0378-5173(93)90222-2]
[35]
Bothiraja C, Dhage K, Kamble R. D-α-Tocopherol polyethylene glycol succinate and stearoylmacrogol glycerides biomaterial based nanostructured mixed micelles as nose-to-brain targeting drug delivery system Mater Technol 2022; 37(6): 397-410.
[http://dx.doi.org/10.1080/10667857.2020.1854517]
[36]
Wei L, Sun P, Nie S, Pan W. Preparation and evaluation of SEDDS and SMEDDS containing carvedilol. Drug Dev Ind Pharm 2005; 31(8): 785-94.
[http://dx.doi.org/10.1080/03639040500216428] [PMID: 16221613]
[37]
Elnaggar YSR, El-Massik MA, Abdallah OY. Self-nanoemulsifying drug delivery systems of tamoxifen citrate: Design and optimization. Int J Pharm 2009; 380(1-2): 133-41.
[http://dx.doi.org/10.1016/j.ijpharm.2009.07.015] [PMID: 19635537]
[38]
Li J, Zhang X, Jiang J, et al. Systematic assessment of the toxicity and potential mechanism of grapheme derivatives in vitro and in vivo. Toxicol Sci 2019; 167(1): 269-81.
[http://dx.doi.org/10.1093/toxsci/kfy235]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy