Login Register Cart 0
Generic placeholder image

Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

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

Formulation, Optimization and Evaluation of Dabigartan Etexilate Encapsulated Solid Supersaturated Self-Nanoemulsifying Drug Delivery System

Author(s): Nithya Shanthi*, Heena Mittal, Manish Kumar, Arun Kumar Mahato and Brahmeshwar Mishra

Volume 14, Issue 2, 2024

Published on: 19 January, 2024

Page: [143 - 154] Pages: 12

DOI: 10.2174/0124681873276409231213115328

Price: $65

Abstract

Objective: The present study proposed Dabigatran Etexilate loaded solid supersaturated self-nanoemulsifying drug delivery system (solid S-SNEDDS) for enhancement of payload, drug solubility, dissolution rate as well as minimization of drug precipitation.

Methods: The study involved formulation optimization using the Box-Behnken design. The optimal SNEDDS consisting of Caprylic acid (32.9% w/w), Cremophor EL (50.2% w/w) and Transcutol HP (18.8% w/w) as Oil, Surfactant and Co-surfactant, respectively were formulated and evaluated for particle size, PDI, Zeta potential and saturation solubility. The SNEDDS was further incorporated with PPIs for the preparation of supersaturated SNEDDS (S-SNEDDS) to increase the drug payload in the formulation. S-SNEDDS was converted to solid S-SNEDDS by adsorption onto the porous carrier i.e., Aerosil®200. The in-vitro drug release study was also conducted for solid S-SNEDDS.

Results: SNEDDS had size, PDI, and Zeta potential of 82 nm, 0.347, -10.50 mV, respectively. SNEDDS enhanced the saturation solubility of the drug by 93.65-fold. Among PPIs, HPMC K4M showed the most effective response for the formulation of S-SNEDDS. The S-SNEDDS had a more substantial drug payload, which further increased the solubility by 150 times of pure drugs and 16 times of SNEDDS. Solid S-SNEDDS exhibited free-flowing properties. Reconstituted solid S-SNEDDS had acceptable size, PDI, and Zeta potential of 131.3 nm, 0.457, and -11.3 mV, respectively. In-vitro drug release study revealed higher drug dissolution and minimized drug precipitation by SNEDDS compared to marketed products and pure drugs.

Conclusion: Proposed nano-formulation was found to efficiently improve the aqueous solubility of the drug and avoid the drug precipitation, thereby avoiding drug loss and improving drug bioavailability.

Keywords: Nanoemulsion, supersaturated self-nanoemulsifying drug delivery system, solubility, bioavailability, drug delivery, nanomedicine.

« Previous Next »
Graphical Abstract

[1]
Chai F, Sun L, Ding Y, et al. A solid self-nanoemulsifying system of the BCS class IIb drug dabigatran etexilate to improve oral bioavailability. Nanomedicine 2016; 11(14): 1801-6.
[http://dx.doi.org/10.2217/nnm-2016-0138]
[2]
Halton J, Brandão LR, Luciani M, et al. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): A randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol 2021; 8(1): e22-33.
[http://dx.doi.org/10.1016/S2352-3026(20)30368-9 ] [PMID: 33290737]
[3]
Hu M, Zhang J, Ding R, Fu Y, Gong T, Zhang Z. Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system. Drug Dev Ind Pharm 2017; 43(4): 687-97.
[http://dx.doi.org/10.1080/03639045.2016.1278015 ] [PMID: 28032534]
[4]
Cho JH, Kim JC, Kim HS, et al. Novel dabigatran etexilate hemisuccinate-loaded polycap: Physicochemical characterisation and in vivo evaluation in beagle dogs. Int J Pharm 2017; 525(1): 60-70.
[http://dx.doi.org/10.1016/j.ijpharm.2017.04.028] [PMID: 28414137]
[5]
Zheng C, Li Y, Peng Z, et al. A composite nanocarrier to inhibit precipitation of the weakly basic drug in the gastrointestinal tract. Drug Deliv 2020; 27(1): 712-22.
[http://dx.doi.org/10.1080/10717544.2020.1760402 ] [PMID: 32397763]
[6]
Date AA, Hanes J, Ensign LM. Nanoparticles for oral delivery: Design, evaluation and state-of-the-art. J Control Release 2016; 240: 504-26.
[http://dx.doi.org/10.1016/j.jconrel.2016.06.016] [PMID: 27292178]
[7]
Date AA, Desai N, Dixit R, Nagarsenker M. Self-nanoemulsifying drug delivery systems: Formulation insights, applications and advances. Nanomedicine 2010; 5(10): 1595-616.
[http://dx.doi.org/10.2217/nnm.10.126] [PMID: 21143036]
[8]
Nazlı H, Mesut B, Özsoy Y. In vitro evaluation of a solid supersaturated self nanoemulsifying drug delivery system (Super-SNEDDS) of aprepitant for enhanced solubility. Pharmaceuticals 2021; 14(11): 1089.
[http://dx.doi.org/10.3390/ph14111089] [PMID: 34832871]
[9]
Krstić M, Medarević Đ, Đuriš J, Ibrić S. Self-nanoemulsifying drug delivery systems (SNEDDS) and self-microemulsifying drug delivery systems (SMEDDS) as lipid nanocarriers for improving dissolution rate and bioavailability of poorly soluble drugs. In: Grumezescu AM, Ed Lipid Nanocarriers for Drug Targeting. William Andrew Publishing 2018; pp. 473-508.
[10]
Jain S, Kambam S, Thanki K, Jain AK. Cyclosporine A loaded self-nanoemulsifying drug delivery system (SNEDDS): Implication of a functional excipient based co-encapsulation strategy on oral bioavailability and nephrotoxicity. RSC Advances 2015; 5(61): 49633-42.
[http://dx.doi.org/10.1039/C5RA04762E]
[11]
Karavasili C, Andreadis II, Tsantarliotou MP, et al. Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) containing rice bran oil for enhanced fenofibrate oral delivery: In vitro digestion, ex vivo permeability, and in vivo bioavailability studies. AAPS PharmSciTech 2020; 21(6): 208.
[http://dx.doi.org/10.1208/s12249-020-01765-2] [PMID: 32725343]
[12]
Mahapatra AK, Murthy PN, Swadeep B, Swain RP. Self-emulsifying drug delivery systems (SEDDS): An update from formulation development to therapeutic strategies. Int J Pharm Tech Res 2014; 6: 546-68.
[13]
Kumar M, Shanthi N, Mahato AK, Soni S, Rajnikanth PS. Preparation of luliconazole nanocrystals loaded hydrogel for improvement of dissolution and antifungal activity. Heliyon 2019; 5(5): e01688.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01688] [PMID: 31193099]
[14]
Yadav P, Rastogi V, Verma A. Application of Box-Behnken design and desirability function in the development and optimization of self-nanoemulsifying drug delivery system for enhanced dissolution of ezetimibe. Future Journal of Pharmaceutical Sciences 2020; 6(1): 7.
[http://dx.doi.org/10.1186/s43094-020-00023-3]
[15]
Subramanian P, Rajnikanth PS, Kumar M, Chidambram K. In-vitro and in-vivo evaluation of supersaturable self-nanoemulsifying drug delivery system (SNEDDS) of dutasteride. Curr Drug Deliv 2020; 17(1): 74-86.
[http://dx.doi.org/10.2174/1567201816666191112111610] [PMID: 31721703]
[16]
Bannow J, Yorulmaz Y, Löbmann K, Müllertz A, Rades T. Improving the drug load and in vitro performance of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) using polymeric precipitation inhibitors. Int J Pharm 2020; 575: 118960.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118960] [PMID: 31846728]
[17]
Sanka K, Suda D, Bakshi V. Optimization of solid-self nanoemulsifying drug delivery system for solubility and release profile of clonazepam using simplex lattice design. J Drug Deliv Sci Technol 2016; 33: 114-24.
[http://dx.doi.org/10.1016/j.jddst.2016.04.003]
[18]
Arlt B. 2022. Available from: https://tapellets.com/index.php/dabigatran-formulation-for-oral-administration-an-evaluation/
[19]
Singh Y, Meher JG, Raval K, et al. Nanoemulsion: Concepts, development and applications in drug delivery. J Control Release 2017; 252: 28-49.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.008] [PMID: 28279798]
[20]
Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: An advanced mode of drug delivery system. 3 Biotech 2015; 5: 123-7.
[http://dx.doi.org/10.1007/s13205-014-0214-0]
[21]
Danaei M, Dehghankhold M, Ataei S, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018; 10(2): 57.
[http://dx.doi.org/10.3390/pharmaceutics10020057 ] [PMID: 29783687]
[22]
Midekessa G, Godakumara K, Ord J, et al. Zeta Potential of Extracellular Vesicles: Toward understanding the attributes that determine colloidal stability. ACS Omega 2020; 5(27): 16701-10.
[http://dx.doi.org/10.1021/acsomega.0c01582] [PMID: 32685837]
[23]
Samimi S, Maghsoudnia N, Eftekhari RB, Dorkoosh F. Lipid-Based Nanoparticles for Drug Delivery Systems. In: Mohapatra SS, Ranjan S, Dasgupta N, Mishra RK, Thomas S, Eds Characterization and Biology of Nanomaterials for Drug Delivery. Elsevier 2019; pp. 47-76.
[http://dx.doi.org/10.1016/B978-0-12-814031-4.00003-9]
[24]
Balakumar K, Raghavan CV, selvan NT, prasad RH, Abdu S. Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf B Biointerfaces 2013; 112: 337-43.
[http://dx.doi.org/10.1016/j.colsurfb.2013.08.025] [PMID: 24012665]
[25]
Basalious EB, Shawky N, Badr-Eldin SM. SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: Development and optimization. Int J Pharm 2010; 391(1-2): 203-11.
[http://dx.doi.org/10.1016/j.ijpharm.2010.03.008] [PMID: 20214965]
[26]
Nasr A, Gardouh A, Ghorab M. Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: Design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics 2016; 8(3): 20.
[http://dx.doi.org/10.3390/pharmaceutics8030020] [PMID: 27355963]
[27]
Singh D, Singh M, Tharmatt A, Tiwary AK, Bedi N. Polymeric precipitation inhibitor as an effective trigger to convert supersaturated into supersaturable state in vivo. Ther Deliv 2019; 10(9): 599-608.
[http://dx.doi.org/10.4155/tde-2019-0053] [PMID: 31646935]
[28]
Kostelanská K, Prudilová BB, Holešová S, Vlček J, Vetchý D, Gajdziok J. Comparative study of powder carriers physical and structural properties. Pharmaceutics 2022; 14(4): 818.
[http://dx.doi.org/10.3390/pharmaceutics14040818 ] [PMID: 35456652]
[29]
Singh H, Nathani S, Singh N, et al. Development and characterization of Solid-SNEDDS formulation of DHA using hydrophilic carrier with improved shelf life, oxidative stability and therapeutic activity. J Drug Deliv Sci Technol 2019; 54: 101326.
[http://dx.doi.org/10.1016/j.jddst.2019.101326]
[30]
Diaz DA, Colgan ST, Langer CS, Bandi NT, Likar MD, Van Alstine L. Dissolution similarity requirements: How similar or dissimilar are the global regulatory expectations? AAPS J 2016; 18(1): 15-22.
[http://dx.doi.org/10.1208/s12248-015-9830-9] [PMID: 26428517]

Rights & Permissions Print Cite
Article Metrics
12
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy