Generic placeholder image

Pharmaceutical Nanotechnology


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

Research Article

Solid Lipid Nanoparticles of Dronedarone Hydrochloride for Oral Delivery: Optimization, In Vivo Pharmacokinetics and Uptake Studies

Author(s): Vaishali M. Gambhire*, Makarand S. Gambhire and Nisharani S. Ranpise

Volume 7 , Issue 5 , 2019

Page: [375 - 388] Pages: 14

DOI: 10.2174/2211738507666190802140607


Background: Dronedarone HCl (DRD), owing to its poor aqueous solubility and extensive presystemic metabolism shows low oral bioavailability of about 4% without food, which increases to approximately 15% when administered with a high fat meal.

Objective: Solid lipid nanoparticles (SLN) were designed with glyceryl monstearate (GMS) in order to improve oral bioavailability of DRD.

Methods: Hot homogenization followed by probe sonication was used to prepare SLN dispersions. Box-Behnken design was used to optimize manufacturing conditions. SLN were characterized for particle size, zeta potential, entrapment efficiency, physical state and in vitro drug release. Pharmacokinetics and intestinal uptake study of dronedarone HCl loaded solid lipid nanoparticles (DRD-SLN) in the presence and absence of endocytic uptake inhibitor, chlorpromazine (CPZ) was performed with conscious male Wistar rats.

Results: Optimized formulation of SLN showed particle size of 233 ± 42 nm and entrapment efficiency of 87.4 ± 1.29%. Results of pharmacokinetic studies revealed enhancement of bioavailability of DRD by 2.68 folds from SLN as compared to DRD suspension. Significantly reduced bioavailability of DRD-SLNs in the presence of chlorpromazine, demonstrated the role of endocytosis in uptake of SLN formulation.

Conclusion: These results indicated that dronedarone HCl loaded SLN could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first pass metabolism.

Keywords: Bioavailability, dronedarone hydrochloride, first pass metabolism, lymphatic uptake, SLNs, glyceryl monstearate.

Graphical Abstract
Doggrell SA, Hancox JC. Dronedarone: an amiodarone analogue. Expert Opin Investig Drugs 2004; 13(4): 415-26.
Pamukcu B, Lip GY. Dronedarone as a new treatment option for atrial fibrillation patients: pharmacokinetics, pharmacodynamics and clinical practice. Expert Opin Pharmacother 2011; 12(1): 131-40.
Mahapatra AK, Samoju S, Patra RK, Murthy PN. Dissolution enhancement of dronedarone hydrochloride by complexation with β-CD and HP β-CD: dissolution and physicochemical characterization. Thaiphesatchasan 2014; 38(3): 139-48.
Han SD, Jung SW, Jang SW, et al. Preparation of solid dispersion of dronedarone hydrochloride with Soluplus(®) by hot melt extrusion technique for enhanced drug release. Chem Pharm Bull 2015; 63(4): 295-9.
Han SD, Jung SW, Jang SW, Son M, Kim BM, Kang MJ. Reduced food-effect on intestinal absorption of dronedarone by selfmicroemulsifying drug delivery system (SMEDDS). Biol Pharm Bull 2015; 38(7): 1026-32.
Yeole BD, Patil RP, Lone KD, Tekade AR. Preparation of nanoparticles of poorly water soluble dronedarone by antisolvent addition technique using natural polymer as a stabilizer. J Pharm Res Clin Pract 2016; 6(4): 8-16.
Chalikwar SS, Belgamwar VS, Talele VR, Surana SJ, Patil MU. Formulation and evaluation of Nimodipine-loaded solid lipid nanoparticles delivered via lymphatic transport system. Colloids Surf B Biointerfaces 2012; 97: 109-16.
Varshosaz J, Minayian M, Moazen E. Enhancement of oral bioavailability of pentoxifylline by solid lipid nanoparticles. J Liposome Res 2010; 20(2): 115-23.
Varshosaz J, Tabbakhian M, Mohammadi MY. Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability. J Liposome Res 2010; 20(4): 286-96.
Aji Alex MR, Chacko AJ, Jose S, Souto EB. Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur J Pharm Sci 2011; 42(1-2): 11-8.
Trevaskis NL, Charman WN, Porter CJ. Lipid-based delivery systems and intestinal lymphatic drug transport: a mechanistic update. Adv Drug Deliv Rev 2008; 60(6): 702-16.
Chakraborty S, Shukla D, Mishra B, Singh S. Lipid--an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm 2009; 73(1): 1-15.
Das S, Ng WK, Kanaujia P, Kim S, Tan RB. Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: effects of process variables. Colloids Surf B Biointerfaces 2011; 88(1): 483-9.
Tran TH, Ramasamy T, Cho HJ, et al. Formulation and optimization of raloxifene-loaded solid lipid nanoparticles to enhance oral bioavailability. J Nanosci Nanotechnol 2014; 14(7): 4820-31.
Gambhire MS, Bhalekar MR, Gambhire VM. Statistical optimization of dithranol-loaded solid lipid nanoparticles using factorial design. Braz J Pharm Sci 2011; 47(3): 503-11.
Gambhire MS, Bhalekar MR, Shrivastava B. Bioavailability assessment of simvastatin loaded solid lipid nanoparticles after oral administration. Asian J Pharm Sci 2011; 6(6): 251-8.
Luo Y, Chen D, Ren L, Zhao X, Qin J. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Control Release 2006; 114(1): 53-9.
Gambhire VM, Salunkhe SM, Gambhire MS. Atorvastatin-loaded lipid nanoparticles: antitumor activity studies on MCF-7 breast cancer cells. Drug Dev Ind Pharm 2018; 44(10): 1685-92.
Roger E, Lagarce F, Garcion E, Benoit JP. Lipid nanocarriers improve paclitaxel transport throughout human intestinal epithelial cells by using vesicle-mediated transcytosis. J Control Release 2009; 140(2): 174-81.
Roger E, Lagarce F, Garcion E, Benoit JP. Biopharmaceutical parameters to consider in order to alter the fate of nanocarriers after oral delivery. Nanomedicine 2010; 5(2): 287-306.
Sahay G, Alakhova DY, Kabanov AV. Endocytosis of nanomedicines. J Control Release 2010; 145(3): 182-95.
Ali Khan A, Mudassir J, Mohtar N, Darwis Y. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations. Int J Nanomedicine 2013; 8: 2733-44.
Kheradmandnia S, Vasheghani-Farahani E, Nosrati M, Atyabi F. Preparation and characterization of ketoprofen-loaded solid lipid nano-particles made from beeswax and carnauba wax. Nanomedicine: nanotech. Biol Med 2010; 6(6): 753-9.
Das S, Ng WK, Tan RB. Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs? Eur J Pharm Sci 2012; 47(1): 139-51.
Ramasamy T, Khandasami US, Ruttala H, Shanmugam S. Development of solid lipid nanoparticles enriched hydrogels for topical delivery of anti-fungal agent. Macromol Res 2012; 20(7): 682-92.
Bikkad ML, Nathani AH, Mandlik SK, Shrotriya SN, Ranpise NS. Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting by topical delivery. J Liposome Res 2014; 24(2): 113-23.
Bunjes H, Westesen K, Koch MHJ. Crystallization tendency and polymorphic transitions in triglyceride nanoparticles. Int J Pharm 1996; 129: 159-73.
Xie S, Zhu L, Dong Z, et al. Preparation, characterization and pharmacokinetics of enrofloxacin-loaded solid lipid nanoparticles: influences of fatty acids. Colloids Surf B Biointerfaces 2011; 83(2): 382-7.

© 2022 Bentham Science Publishers | Privacy Policy