SOLID LIPID NANOPARTICLES OF REBAMIPIDE: FORMULATION, CHARACTERIZATION AND IN VIVO PHARMACOKINETIC EVALUATION

Authors

  • MIRMEERA NIHARIKA GIRISH Department of Pharmacy, Annamalai University, Tamilnadu https://orcid.org/0000-0002-7490-6070
  • KANNAN K. Department of Pharmacy, Annamalai University, Tamilnadu

DOI:

https://doi.org/10.22159/ijap.2022v14i2.42945

Keywords:

Solid lipid nanoparticles, rebamipide, bioavailability, pharmacokinetics, homogenization and ultrasonication.

Abstract

Objective: Rebamipide (REB) is a gastroprotective agent used to treat ulcers and gastritis throughout the stomach. Rebamipide is a BCS class IV drug with low oral bioavailability of less than 10%. The objective of this study was to develop an REB-SLNs formulation for oral administration to improve the bioavailability of rebamipide.

Methods: The hot homogenization and ultrasonication methods were used to prepare the REB-SLNs. Lipids are dynasan 114, dynasan 116, dynasan 114, imwitor 900 P. Non-ionic surfactants are poloxamer 188, polysorbate 80, and lipoid E 80 act as an amphoteric stabilizing agent used in the formulation. Developed SLNs were evaluated for particle size, PDI, zeta potential, entrapment efficiency, drug content, invitro release, stability studies, and invivo pharmacokinetic profile.

Results: The optimized REB SLNs (F9) formulation prepared with Dynassan 114 contains an average particle size of 234 ± 3.5nm, PDI of 0.228 ± 0.05, ZP of -24.58 ± 2.63mV, drug content of 99.89 ± 0.04%, and entrapment efficiency of 96.15 ± 0.32%. DSC studies revealed that no interactions occurred between drug and excipients. SEM studies showed that SLNs were nearly spherical. In vitro drug release of the optimized formulation, F9 was 91.61% in 24 hours as sustained drug release. The optimized formulation was stable under refrigeration and room temperature for three months. Invivo pharmacokinetic studies of optimized formulation (F9) exhibited higher Cmax and AUC values relative to the coarse suspension.  

Conclusion: Compared to the reference standard coarse suspension, the relative bioavailability of the developed formulation of REB-SLNs of dynasan 114 and combination of poloxamer 188 and polysorbate 80 (F9) was increased by 3.87 times.

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References

Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009; 71:349–58.

Akanksha G, Deepti S, Navneet G. Solid Lipid Nanoparticles (SLN): method, characterization and applications. Int Curr Pharm J 2012; 11:384- 393.

Pardeike J, Hommoss A, Muller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm 2009; 366: 170–184.

Genta RM. The role of rebamipide in the management of inflammatory disease of the gastrointestinal tract. Aliment Pharmacol Ther 2003; 18: 8–13.

Nethra vani G, Alagusundaram M, Chandrasekar KB. Formulation and optimization and in vitro characterization of olanzapine liposome. Int J App Pharm 2021; 13:109-114.

Tung NT, Park CW, Oh TO, Kim JY, Ha JM, Rhee YS, et al. formulation of solid dispersion of rebamipide evaluated in a rat model for improved bioavailability and efficacy. J Pharm Pharmacol 2011; 63: 1539–47.

Narendar D, Kishan V. Improved anti hyperlipidemic activity of rosuvastatin calcium via lipid nanoparticles: pharmacokinetic and pharmacodynamic evaluation. Eur J Pharm Biopharm 2016; 110: 47-57.

Zielinska A, Ferreira NR, Durazzo A, Lucarini M, Cicero N, Mamouni SE. Development and optimization of alpha-pinene-loaded solid lipid nanoparticles (SLN) using experimental factorial design and dispersion analysis. Molecules 2019; 24: 2683-2693.

Qushawy M, Prabahar K, Abd-Alhaseeb M, Swidan S, Nasr A. Preparation and evaluation of carbamazepine solid lipid nanoparticle for alleviating seizure activity in pentylenetetrazole-kindled mice. Molecules 2019; 24: 3971-3979.

Kim KT, Lee J-Y, Park J-H, Cho H-J, Yoon I-S, Kim D-D. Capmul MCM/Solutol HS15 based microemulsion for enhanced oral bioavailability of rebamipide. J Nanosci Nanotechnol 2017; 17: 2340–2344.

Yu G, Yongjun W, Lu X. Enhanced bioavailability of rebamipide nanocrystal tablets: Formulation and in vitro/in vivo evaluation. Asian J Pharm Sci 2015; 10: 223-229.

Suvarna GB, Rajendra PM. Rosuvastatin calcium loaded chitosan nanoparticles: preparation evaluation and in vitro release studies. Int J App Pharm 2020; 12:95-102.

Hu FQ, Yuan H, Zhang HH, Fang M. Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int J Pharm 2002; 239: 121-128.

Anasuya P, Pranoti K. Formulation and evaluation of antifungal nanogel for topical drug delivery system. Asian J Pharm Clin Res. 2021; 14:127-134.

Yamasa K, Ishiyama H, Imaizumi. Effect of OPC-12759, a novel antiulcer agent, on chronic and acute experimental gastric ulcer and gastric secretion in rats. Jpn J Pharmacol 1989; 49 (4): 441-448.

Bhaskar K, Anbu J, Ravichandiran V, Venkateswarlu V, Rao YM. Lipid nanoparticles for transdermal delivery of flurbiprofen: Formulation, in vitro, ex vivo and in vivo studies. Lipids Health Dis 2009; 8: 6-14.

Harshad H, Manasmita D, Sanyog J. Solid lipid nanoparticles: An oral bioavailability enhancer vehicle. Expert Opin. Drug Delivery 2011; 8:1407-1424.

Daniela C, Marina G, Elena P, Luigi B, Loredana S and Michele T. Formulation of curcumin-loaded solid lipid nanoparticles produced by fatty acids coacervation technique. J Microencapsulation 2011; 28: 537-548.

Olbrich, Oliver K, Muller RH. Enzymatic degradation of Dynasan 114 SLN effect of surfactants and particle size. J Nanopart Tech App Res 2002; 4: 121–129.

Shuyu X, Luyan Z, Zhao D, Yan W, Xiaofang W, and WenZhong Z. Preparation and evaluation of ofloxacin-loaded palmitic acid solid lipid nanoparticles. Int J Nano med 2011; 6: 547–555.

Published

23-12-2021

How to Cite

NIHARIKA GIRISH, M., & K., K. (2021). SOLID LIPID NANOPARTICLES OF REBAMIPIDE: FORMULATION, CHARACTERIZATION AND IN VIVO PHARMACOKINETIC EVALUATION. International Journal of Applied Pharmaceutics, 14(2). https://doi.org/10.22159/ijap.2022v14i2.42945

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