Abstract
Combination of long and medium chain lipids show different behavior in-vivo and contribute differently for bioavailability. Aim of the present study was to evaluate the effect of long chain- (LCFA) and medium-chain (MCFA) fatty acid lipids on the bioavailability of rosuvastatin from rosuvastatin loaded nanostructured lipid carrier (RNLC). Lauric acid and capryol-90™ were selected as MCFA whereas stearic acid and oleic acid were chosen as LCFA. RNLC was prepared using melt-emulsification–ultrasonication method using different combinations of MCFA and LCFA. Non-ionic, non-toxic MYS-25 was used as stabilizing agent. RNLC showed entrapment efficiency of 85–92% denoting it to be beneficial for prolonged release of drug after oral administration. Zeta potential of −26.79 mV signifies particle stability through the repulsive forces which prevents aggregation upon storage. In-vivo oral pharmacokinetic study demonstrated six to ninefold improvement in the bioavailability of rosuvastatin (RSVS) in the form of RNLC than RSVS-Aqueous dispersion. A 1.5-fold increase in bioavailability was observed when RNLC was prepared with LCFA solid lipid and MCFA liquid lipid combination as compared to RNLC prepared using only MCFA as both solid and liquid lipid. Use of LCFA and MCFA combination was found to be superior as lipid mixture for the RNLC.
Similar content being viewed by others
References
Chakraborty S, Shukla D, Mishra B, Singh S (2009) Lipid—an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm 73:1–15
Chen CC, Tsai TH, Huang ZR, Fang JY (2010) Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: physicochemical characterization and pharmacokinetics. Eur J Pharm Biopharm 74:474–482
Chormale SB, Vavia PR (2012) Development and evaluation of stable solid self-micro emulsifying drug delivery system of rosuvastatin. IPC 64th 2012
Chougule M, Padhi, Misra A (2007) Nano-liposomal dry powder inhaler of tacrolimus: preparation, characterization, and pulmonary pharmacokinetics. Int J Nanomed 2:675–688
Clark AM, Jepson MA, Hirst BH (2001) Exploiting M cells for drug and vaccine delivery. Adv Drug Deliv Rev 50:81–106
Costa P, Lobo JMS (2001) Modeling and comparison of dissolution profiles. Eur J Pharm Sci 13:123–133
Devani M, Ashford M, Craig DQ (2004) The emulsification and solubilisation properties of polyglycolysed oils in self-emulsifying formulations. J Pharm Pharmacol 56:307–316
Gershanik T, Benita S (2000) Self-dispersing lipid formulations for improving oral absorption of lipophillic drugs. Eur J Pharm Biopharm 50:179–188
Grove M, Mullertz A, Nielsen JL, Pedersen GP (2006) Bioavailability of seocalcitol II: development and characterization of self-microemulsifying drug delivery systems (SMEDDS) for oral administration containing medium and long chain triglycerides. Eur J Pharm Sci 28:233–242
Hac-Wydro K, Wydro P (2007) The influence of fatty acids on model cholesterol/phospholipid membranes. Chem Phys Lipids 150:66–81
Han S, Yao T, Zhang X, Gan L, Zhu C, Yu H, Gan Y (2009a) Lipid-based formulations to enhance oral bioavailability of the poorly water-soluble drug anethol trithione: effects of lipid composition and formulation. Int J Pharm 379:18–24
Han HF, Yao TT, Zhang XX, Gan L, Zhu C, Yu HZ, Gan Y (2009b) Lipid-based formulations to enhance oral bioavailability of the poorly water-soluble drug anethol trithione: effects of lipid composition and formulation. Int J Pharm 379:18–24
Hauss DJ, Fogal SE, Ficorilli JV, Price CA, Roy T, Jayaraj AA, Keirns JJ (1998) Lipid-based delivery systems for improving the bioavailability and lymphatic transport of a poorly water-soluble LTB4 inhibitor. J Pharm Sci 87:164–169
Honary S, Zahir F (2013) Effect of zeta potential on the properties of nano-drug delivery systems—a review (Part 2). Trop J Pharm Res 12:265–273
http://www.acessdata.fda.gov/drugsatfda_docs/nda/2013/21-366_Pharmr_P1.pdf. Accessed on 10 May 2017
Hussain N, Jaitley V, Florence AT (2001) Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Adv Drug Deliv Rev 50:107–142
Jantratid E, Janssen N, Reppas C, Dressman JB (2008) Dissolution media simulating conditions in the proximal human git: an update. Pharm Res 25(7):1663–1676
Jia LJ, Zhang DR, Li ZY, Duan CX, Wang YC, Feng FF, Wang FH, Liu Y, Zhang Q (2010) Nanostructured lipid carriers for parenteral delivery of silybin: biodistribution and pharmacokinetic studies. Colloids Surf B 80:213–218
Khoo S, Humberstone AJ, Christopher JHP, Edwards GA, Charman WN (1998) Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm 167:155–164
Kumar TR, Shitut NR, Kumar PK, Vinu MC, Kumar VV, Mullangi R, Srinivas NR (2006) Determination of rosuvastatin in rat plasma by HPLC: validation and its application to pharmacokinetic studies. Biomed Chromatogr 20:881–887
Kumbhar DD, Pokharkar VB (2013) Engineering of nanostructured lipid carrier of the poorly water-soluble drug, bicalutamide: physicochemical investigations. Colloids Surf A 416:32–42
Kuo YC, Chung JF (2011) Physicochemical properties of nevirapine loaded solid lipid nanoparticles and nanostructured lipid carriers. Colloids Surf B 83:299–306
Lennernas H (1998) Human intestinal permeability. J Pharm Sci 87:403–410
Li X, Nie SF, Kong J, Li N, Ju CY, Pan WS (2008) A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers. Int J Pharm 363:177–182
Li X, Gu L, Xu Y, Wang Y (2009) Preparation of fenofibrate nanosuspension and study of its pharmacokinetic behavior in rats. Drug Dev Ind Pharm 35:827–833
Liu DH, Liu ZH, Wang LL, Zhang C, Zhang N (2011) Nanostructured lipid carriers as novel carrier for parenteral delivery of docetaxel. Colloids Surf B 85:262–269
Luo Y, Chen D, Ren L, Zhao X, Qin J (2006) Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J Control Release 114:53–59
Majumdar S, Mitra A (2006) Chemical modification and formulation approaches to elevated drug transport across cell membranes. Expert Opin Drug Deliv 3:511–527
Matulka RA, Thompson DV, Burdock GA (2009) Lack of toxicity by medium chain triglycerides (MCT) in canines during a 90-day feeding study. Food Chem Toxicol 47:35–39
Mehnert W, Mäder K (2001) Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliver Rev 47:165–196
Müller RH, Mäder K, Gohla S (2000) Solid lipid nanoparticles (SLN) for controlled drug delivery: a review of the state of the art. Eur J Pharm Biopharm 50:161–177
Müller RH, Radtke M, Wissing SA (2002) Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm 242:121–128
Ochiai A, Ohkuma M, Danjo K (2012) Investigation of surfactants suitable for stabilizing of latanoprost. Int J Pharm 436:732–737
Odeberg JM, Kaufmann P, Kroon KG, Höglund P (2003) Lipid drug delivery and rational formulation design for lipophilic drugs with low oral bioavailability applied to cyclosporine. Eur J Pharm Sci 20:375–382
Pardeike J, Webera S, Haber T, Wagner J, Zarfl HP, Plank H, Zimmer A (2011) Development of an Itraconazole-loaded nanostructured lipid carrier (NLC) formulation for pulmonary application. Int J Pharm 419:329–338
Patel BZ, Patel KS, Shah AS, Surti NI (2012) Preparation and optimization of microemulsion of rosuvastatin calcium. J Pharmacy Bioallied Sci 4:S118–S119
Ruan LP, Chen S, Yu BY, Zhu DN, Cordell GA, Qiu SX (2006) Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. Eur J Med Chem 41:605–610
Ruckenstein E, Shulgin I (2005) Solubility of drugs in aqueous solutions Part 5, Thermodynamic consistency tests for the solubility data. Int J Pharm 292:87–94
Song KH, Chung SJ, Shim CK (2005) Enhanced intestinal absorption of salmon calcitonin (sCT) from proliposomes containing bile salts. J Control Rel 106:298–308
Ton MN, Chang C, Carpentier YA, Deckelbaum RJ (2005) In vivo and in vitro properties of an intravenous lipid emulsion containing only medium chain and fish oil triglycerides. Clin Nutr 24:492–501
Trevaskis NL, Charman WN, Porter CJH (2008) Lipid-based delivery systems and intestinal lymphatic drug transport: a mechanistic update. Adv Drug Deliv Rev 60:702–716
Tsai MJ, Wu PC, Huang YB, Chang JS, Lin CL, Tsai YH, Fang JY (2012) Baicalein loaded in tocol nanostructured lipid carriers (tocol NLCs) for enhanced stability and brain targeting. Int J Pharm 423:461–470
Venkatesan N, Uchino K, Amagase K, Ito Y, Shibata N, Takada K (2006) Gastrointestinal patch system for the delivery of erythropoietin. J Control Rel 111:19–26
Zheng M, Falkeborg M, Zheng Y, Yang T, Xua X (2013) Formulation and characterization of nanostructured lipid carriers containing a mixed lipids core. Colloids Surf A 430:76–84
Zhuang CY, Li N, Wang M, Zhang XN, Pan WS, Peng JJ, Pan YS, Tang X (2010) Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm 394:179–185
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors report no declaration of interest.
Rights and permissions
About this article
Cite this article
Pokharkar, V., Patil-Gadhe, A. & Kaur, G. Physicochemical and pharmacokinetic evaluation of rosuvastatin loaded nanostructured lipid carriers: influence of long- and medium-chain fatty acid mixture. J. Pharm. Investig. 48, 465–476 (2018). https://doi.org/10.1007/s40005-017-0342-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40005-017-0342-8