Rosuvastatin calcium-loaded Solid Lipid Nanoparticles (SLN) using design of experiment approach for oral delivery

  • Anjali Beniwal G & W Labs, Department of Product Development, South Plainfield, New Jersey-07080
  • Hema Choudhary PDM college of Pharmacy affiliated by Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Haryana
Keywords: Solid Lipid Nanoparticle, Rosuvastatin, Controlled Release, Nanoparticles, Lipid based delivery, DoE, Hyperlipidemia, Drug Delivery, Quality by design (QbD), Sustained Drug Delivery


This investigation utilizes quality-by-design approach to develop the Rosuvastatin Calcium (Rst)-loaded solid lipid nanoparticles (SLN). Effect of formulation variables such as amount of lipid (200-500 mg stearic acid) and surfactant concentration (0.5-2.0% PVA) were studied. Design of Experiment (DoE) was used to quantify the extent of impact of lipid amount and surfactant concentration on the physicochemical properties of the SLN and to identify optimized SLN formulation. It was observed that interplay of formulation variables had significant effect on particle size (198.25 to 622.36 nm), %EE (28.82 to 35.87%) and In vitro release (44.87 to 64.29%). Based on the results, point optimization was carried out to obtain the SLN with minimum particle size (202.5 ± 9.29 nm), maximum %EE (34.78 ± 0.37 %) and sustained In vitro release (57.3 ± 2.6 % at 36 hours) within the design space. In vitro drug release data fitted well in Korsmeyer-peppas model indicating the fickian diffusion mechanism. Ex vivo studies indicated sustained permeation of the Ropt compared to the control. Furthermore, stability studies indicated Ropt formulation exhibited no significant physical or chemical change under accelerated conditions.


Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N Engl J Med [Internet]. 2008 Nov 20;359(21):2195–207. Available from:

Tiwari R, Pathak K. Statins therapy: a review on conventional and novel formulation approaches. J Pharm Pharmacol [Internet]. 2011 Aug;63(8):983–98. Available from:

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 Surfaces B Biointerfaces [Internet]. 2013 Dec 1;112:337–43. Available from:

Jain S, Patel N, Lin S. Solubility and dissolution enhancement strategies: current understanding and recent trends. Drug Dev Ind Pharm [Internet]. 2015 Jun 3;41(6):875–87. Available from:

Kapure VJ, Pande V V., Deshmukh PK. Dissolution Enhancement of Rosuvastatin Calcium by Liquisolid Compact Technique. J Pharm [Internet]. 2013 Feb 27;2013:1–9. Available from:

Patel ZB, Patel KS, Shah AS, Surti NI. Preparation and optimization of microemulsion of rosuvastatin calcium. J Pharm Bioallied Sci [Internet]. 2012 Mar; 4 (Suppl 1):S118-9. Available from:

Shah MK, Madan P, Lin S. Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration. Pharm Dev Technol [Internet]. 2013;1083–7450. Available from:

Bunjes H. Lipid nanoparticles for the delivery of poorly water-soluble drugs. J Pharm Pharmacol [Internet]. 2010 Nov 1;62(11):1637–45. Available from:

Hu L, Xing Q, Meng J, Shang C. Preparation and Enhanced Oral Bioavailability of Cryptotanshinone-Loaded Solid Lipid Nanoparticles. AAPS PharmSciTech [Internet]. 2010 Jun 30; 11(2):582–7. Available from:

Shah MK, Madan P, Lin S. Elucidation of intestinal absorption mechanism of carvedilol-loaded solid lipid nanoparticles using Caco-2 cell line as an in-vitro model. Pharm Dev Technol. 2014;0:1–9.

Jain S, Patel N, Shah MK, Khatri P, Vora N, Paudel KS, et al. Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application. J Pharm Sci. 2016 Nov;0(0):109–31.

Dudhipala N, Veerabrahma K. Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation. Eur J Pharm Biopharm [Internet]. 2017 Jan; 110:47–57. Available from:

Abo Enin HA. Self-nanoemulsifying drug-delivery system for improved oral bioavailability of rosuvastatin using natural oil antihyperlipdemic. Drug Dev Ind Pharm [Internet]. 2015 Jul 3; 41(7):1047–56. Available from:

Shah M. Solid Lipid Nanoparticles (SLN) for Oral Drug Delivery: An Overview. J Nanomed Nanosci [Internet]. 2017; Available from:

Hu L, Tang X, Cui F. Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol. 2004 Dec;56(12):1527–35.

Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci [Internet]. 2009 Jul [cited 2016 Oct 11]; 71(4):349–58. Available from:

Huang Y, Dai W-G. Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B [Internet]. 2014 Feb;4(1):18–25. Available from:

Mehnert W, Mäder K. Solid lipid nanoparticles: Production, characterization and applications. Adv Drug Deliv Rev. 2001; 47(2):165–96.

Jain S, Patel N, Madan P, Lin S. Quality by design approach for formulation, evaluation and statistical optimization of diclofenac-loaded ethosomes via transdermal route. Pharm Dev Technol [Internet]. 2015 May 19; 20(4):473–89. Available from:

Patel N, Jain S, Madan P, Lin S. Application of design of experiments for formulation development and mechanistic evaluation of iontophoretic tacrine hydrochloride delivery. Drug Dev Ind Pharm [Internet]. 2016 Nov 10; 42(11):1894–902. Available from:

Bei Y-Y, Zhou X-F, You B-G, Yuan Z-Q, Chen W-L, Xia P, et al. Application of the central composite design to optimize the preparation of novel micelles of harmine. Int J Nanomedicine [Internet]. 2013; 8:1795–808. Available from:

Vemulapalli V, Banga AK, Friden PM. Optimization of Iontophoretic Parameters for the Transdermal Delivery of Methotrexate. Drug Deliv [Internet]. 2008 Jan 16; 15(7):437–42. Available from:

Agarwal R, Malthar H, Madhumathi C, Chaitanya B. Development and pharmacodynamic evaluation of rosuvastatin-loaded nanostructured lipid carriers for oral. 2015; Available from:

Xinsheng Peng J, Fang X, Zhou Y, Wang J, Guo F, Li F, et al. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. Int J Nanomedicine [Internet]. 2011 Apr;6:683. Available from:

Chen C-C, Tsai T-H, Huang Z-R, Fang J-Y. Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: Physicochemical characterization and pharmacokinetics. Eur J Pharm Biopharm [Internet]. 2010 Mar;74(3):474–82. Available from:

Araújo J, Gonzalez-Mira E, Egea MA, Garcia ML, Souto EB. Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications. Int J Pharm [Internet]. 2010 Jun 30;393(1–2):168–76. Available from:

Ghadiri M, Fatemi S, Vatanara A, Doroud D, Najafabadi AR, Darabi M, et al. Loading hydrophilic drug in solid lipid media as nanoparticles: Statistical modeling of entrapment efficiency and particle size. Int J Pharm [Internet]. 2012 Mar 15;424(1–2):128–37. Available from:

Schubert M, Müller-Goymann C. Solvent injection as a new approach for manufacturing lipid nanoparticles–evaluation of the method and process parameters. Eur J Pharm [Internet]. 2003 [cited 2016 Jun 22]; Available from:

Zhang J, Fan Y, Smith E. Experimental Design for the Optimization of Lipid Nanoparticles. J Pharm Sci [Internet]. 2009 May;98(5):1813–9. Available from:

Varshosaz J, Ghaffari S, Khoshayand MR, Atyabi F, Dehkordi AJ, Kobarfard F. Optimization of freeze-drying condition of amikacin solid lipid nanoparticles using D-optimal experimental design. Pharm Dev Technol [Internet]. 2012 Apr 4;17(2):187–94. Available from:

Ferreira SLC, Bruns RE, da Silva EGP, dos Santos WNL, Quintella CM, David JM, et al. Statistical designs and response surface techniques for the optimization of chromatographic systems. J Chromatogr A [Internet]. 2007 Jul;1158(1–2):2–14. Available from:

Bezerra MA, Santelli RE, Oliveira EP, Villar LS, Escaleira LA. Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta [Internet]. 2008 Sep 15;76(5):965–77. Available from:

Shah R, Eldridge D, Palombo E. Optimisation and stability assessment of solid lipid nanoparticles using particle size and zeta potential. J Phys [Internet]. 2014; Available from:

Parhi R, Suresh P. Preparation and characterization of solid lipid nanoparticles-a review. Curr Drug Discov Technol [Internet]. 2012; Available from:

How to Cite
Beniwal, A., & Choudhary, H. (2017). Rosuvastatin calcium-loaded Solid Lipid Nanoparticles (SLN) using design of experiment approach for oral delivery. International Journal of Chemical and Life Sciences, 6(5), 2029-2038.
Research Articles