1 Department of Pharmaceutical Sciences, Jaipur National University, Jaipur, India
2 Department of Pharmaceutics, AISSMS College of Pharmacy, Pune, India
Abstract Simvastatin is an antihyperlipidemic drug with poor oral bioavailability (<5%) due to the first pass metabolism. Present work has attempted to improve oral bioavailability of simvastatin by incorporating in solid lipid nanoparticles (SLN). The purpose of this research was to study whether the oral bioavailability of simvastatin could be improved by administering simvastatin loaded SLNs. Simvastatin SLNs were developed using compritol 888 ATO by pre-emulsion followed by ultrasonication and characterized by photon correlation spectroscopy, DSC and XRD. Bioavailability studies were conducted in albino rats after oral administration of simvastatin suspension and SLN. Stable simvastatin SLNs having a mean particle size of 245 nm and% entrapment of 72.52% were developed. Simvastatin was dispersed in an amorphous state in the SLN. The results of the in-vitro drug release studies demonstrated significantly slow release of simvastatin (37.08%) from SIMVA-SLN as compared to dispersion of pure drug (97.2%). The relative bioavailability of simvastatin and simvastatin hydroxy acid from SLN were increased by ~164% and ~207% respectively, compared with the reference simvastatin suspension. Thus the study established that the oral bioavailability of simvastatin could be improved by administration as SLN, presumably following digestion of constituting lipids and co-absorption through lymphatic transport. The obtained results are indicative of SLNs as potential carriers for improving the bioavailability of poorly bioavailable drugs such as simvastatin by minimizing first pass metabolism.
Corresponding Authors: Makarand Gambhire, Sinhgad College of Pharmacy, S. No. 44/1, Vadgaon (Bk.), Off. Sinhgad Road, Pune 411041, India.
Tel: +91-94-23085506; Fax: +91-20-24354720
Email: makarandgambhire@gmail.com
Cite this article:
Makarand Gambhire,
Mangesh Bhalekar,
Birendra Shrivastava
.Bioavailability assessment of simvastatin loaded solid lipid nanoparticles after oral administration[J] AJPS, 2011,V6(6): 251-258
Gimeno C, Borja J, Navarro D, et al. In vitro interaction between o?oxacin and cefotaxime against gram-positive and gram-negative bacteria involved in serious infections. Chemotherapy. 1998, 44: 94-98.
[2]
Goldstein E J, Citron DM, Hudspeth M, et al. Trova?oxacin compared with levo?oxacin, o?oxacin, cipro?oxacin, azithromycin and clarithromycin against unusual aerobic and anaerobic human and animal bite-wound pathogens. Antimicrob Chemother. 1998, 41: 391-396.
[3]
Guibert J, Kitzis MD, Acar JF. Antibacterial activity of o?oxacin in urine for 4 days after a single oral dose of 400 mg. Pathol Biol. 1998, 46: 656-660.
[4]
Naber K G, Well M, Hollauer K, et al. In vitro activity of enoxacin versus cipro?oxacin, lome?oxacin, o?oxacin, pe?oxacin, and ru?oxacin against uropathogens. Chemotherapy. 1998, 44: 77-84.
[5]
Onrust S V, Lamb HM, Balfour JA. O?oxacin-a reappraisal of its use in the management of genitourinary tract infections. Drugs. 1998, 56: 895-928.
[6]
Zhang XK, Sun P, Bi R, et al. Targeted delivery of levofoxacin-liposomes for the treatment of pulmonary inflammation. Drug Targeting. 2009, 17: 399-407.
[7]
Cui Y, Zhang Y, Tang X. In vitro and in vivo evaluation of o?oxacin sustained release pellets. Int J Pharm. 2008, 360: 47-52.
[8]
Wang SN, Deng YH, Zheng SH, et al. Studies on preparation of ciprofoxacin liposomes and its tissue distribution in mice. Chin Pharm J. 2003, 38: 274-277.
[9]
Fresta M, Spadaro A, Cerniglia G, et al. Intracellular accumulation of ofoxacin-loaded liposomes in human synovial fbroblasts. Antimicrob Agents Chemother. 1995, 39: 1372-1375.
[10]
Lian T, Ho RJ. Trends and developments in liposome drug delivery systems. J Pharm Sci. 2001, 90: 667-680.
[11]
Gregoriadis G. Liposomes as drug carriers: recent trend and progress. J Pharm Sci. 1989, 78: 693.
[12]
Kremer JMH. Vesicles of varied diameter by a modified injection method. Biochem. 1977, 16: 3932-3935.
[13]
Woundenberg B, Lokerse AF, Kate MT, et al. Liposomes as carriers of antimicrobial agents or I mmunomodulatory agents in the treatment of infections. Eur J Clin Microbiol Infect Dis. 1993, 12: 61-67.
Santos ND, Christine A, Doppen AM. Influence of poly(ethylene glycol) grafting density and polymer length on liposomes: relating plasma circulation lifetimes to protein bind-ing. Biochimica Biophysica Acta. 2007, 1768: 1367-1377.
[16]
Smith AW. Biofilms and antibiotic therapy: is there a role for combating bacterial resistance by the use of novel drug delivery systems? Adv Drug Deliv Rev. 2005, 57: 1539- 1550.
[17]
James A. Karlowsky, Zhanel GG. Concepts on the use of liposomal antimicrobial agents: applications for aminoglycosides. Clin Infect Dis. 1992, 15: 654-667.
[18]
Moghimi SM, Szebenni J. Stealth liposomes and long circulating nanoparticles: critical issues in pharmaco-kinetics, opsonization and protein-binding properties. Prog Lipid Res. 2003, 42: 463-478.
[19]
Schiffelers R, Storm R, Woudenberg IB. Liposome- encapsulated aminoglycosides in pre-clinical and clinical studies. J Antimicro Chemoth. 2001, 48: 333-344.
[20]
Ravichandiran V, Masilamani K, Senthilnathan B. Liposome-a versatile drug delivery system. Der Pharmacia Sinica. 2011, 2: 19-30.
[21]
Cullis PR, Hope MJ, Bally MB. Influence of pH gradients on the transbilayer transport of drugs, lipids, peptides and metal ions into large unilamellar vesicles. Biochim Biophys Acta. 1997, 1331: 187-211.
[22]
Bolotin EM, Cohen R, Bar LK, et al. Ammonium sulphate gradients for efcient and stable remote loading of amphipathic weak bases into liposomes and ligandosomes. J Liposome Res. 1994, 4: 455-479.
[23]
Bangham AD, Horne RW. Negative staining of phospholipids and their structural modifcation by surface active agents as observed in the electron microscope. J Mol Biol. 1964, 8: 660-668.
[24]
Sun WT, Zhang N, Li AG, et al. Preparation and evaluation of N3-O-toluyl-fuorouracil-loaded liposomes. Int J Pharm. 2008, 353: 243-250.
[25]
Huang GH, Zhu XL, Zhang N, et al. Preparation of lomustine thermo-sensitive liposomes and investigation of anti-tumor activity in vitro. Chin Pharm J. 2007, 42: 914-918.
[26]
Song JCH, Huang L, Chen JL. Study on preparation and in vitro release behavior of lung targeting hydroxy-camptothecin liposomes. Chin Pharm J. 2008, 43: 1564-1568.
[27]
Kiln IS, Choi HG, Choi HS, et al. Prolonged systemic delivery of streptokinase using liposome. Arch Pharm Res. 1998, 21: 248-252.
[28]
Unezaki S, Maruyama K, Takahashi N, et al. Enhanced delivery and antitumor acitivty of doxorubicin using long-circulating thermosensitive liposomes containing amphipathic polyethylene glycol in combination with local hyperthermia. Pharm Res. 1994, 11: 1180-1185.
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