Simvastatin-loaded PLGA nanoparticles for improved oral bioavailability and sustained release: Effect of formulation variables

Main Article Content

Aman Soni
Anand Gadad
Panchaxari Dandagi
Vinayak Mastiholimath


The objective of this study was to prepare a nanoparticulate formulation of simvastatin (SV) for improving oral bioavailability and sustaining the drug release while investigating the effect of various formulation parameters on characteristics of nanoparticles. Nanoparticles containing SV were prepared by a modified emulsification solvent evaporation technique using a biodegradable polymer, poly(d,l-lactide-coglycolide) (PLGA) as a sustained release carrier.The effect of various formulation parameters such as drug polymer ratios (SV:PLGA, 1:4 to 1:1), organic solvents (methanol/dichloromethane), and surfactants
(PVA/polysorbate-80) in a fixed concentration (0.5%, w/v) were studied for particle size, drug loading, and entrapment efficiency. Nanoparticles were characterized by differential scanning calorimetry (DSC) and their shapes were observed by scanning electron microscopy (SEM). An aqueous solubility study indicated that the dissolution rates were remarkably increased for nanoparticles compared with the drug alone.The in vitro drug release study of the nanoparticles showed a biphasic release pattern: one initial burst release of 40.56% in the first 4 h which can be helpful to improve the penetration of drug
followed by a second slow-release phase (extended release) consistent with a Higuchi diffusion mechanism.The hypolipidemic activity of nanoparticles was determined in comparison with SV in male Wistar rats for changes in total cholesterol (CH) and triglyceride (TG) levels in blood. Nanoparticles showed a significantly better in vivo performance than SV in reducing total CH and TG levels which is primarily attributed to the improved solubility and dissolution of nanoparticles. Together, these results indicate that nanoparticulate formulations are ideal carriers for oral administration of SV having great potential
to improve the oral bioavailability and sustain the drug release, thereby minimizing the dose-dependent adverse effects and
maximizing the patient’s compliance.


Download data is not yet available.

Article Details

How to Cite
Soni, A., Gadad, A., Dandagi, P., & Mastiholimath, V. (2014). Simvastatin-loaded PLGA nanoparticles for improved oral bioavailability and sustained release: Effect of formulation variables. Asian Journal of Pharmaceutics (AJP), 5(2).


Lipinski CA. Poor aqueous solubility – an industry wide problem in

drug discovery. Am Pharm Rev 2002;53:82-5.

Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to

improve oral bioavailability of poor water soluble drugs. Drug Discov

Today 2007;12:1068-75.

Gursoy RN, Benita S. Selfemulsifying drug delivery systems (SEDDS)

for improved oral delivery of lipophilic drug. Biomed Pharmacother


Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery

of poorly water soluble drugs. Adv Drug Deliv Rev 1997;25:103-28.

Wong SM, Kellaway LW, Murdan S. Enhancement of the dissolution

rate and oral absorption of a poorly water soluble drug by formation

of surfactant-containing microparticles. Int J Pharm 2006;317:61-8.

Kesisoglou F, Panmai S, Wu Y. Nanosizing — Oral formulation

development and biopharmaceutical evaluation. Adv Drug Deliv Rev


Stella VJ, Nti-Addae KW. Prodrug strategies to overcome poor water

solubility. Adv Drug Deliv Rev 2007;59:677-94.

Turk M, Hils P, Helfgen B, Schaber K, Martin H, Wahl MA. Micronization

of pharmaceutical substances by the Rapid Expansion of Supercritical

Solutions (RESS): A promising method to improve bioavailability of

poorly soluble pharmaceutical agents. J Supercrit Fluids 2002;22:75-84.

Rao VM, Nerurka M, Pinnamaneni S, Rinaldi F, Raghavan K.

Co-solubilization of poorly soluble drugs by micellization and

complexation. Int J Pharm 2006;319:98-106.

El-Badry M, Fetih G, Fathy M. Improvement of solubility and dissolution

rate of indomethacin by solid dispersions in Gelucire 50/13 and

PEG4000. Saudi Pharm J 2009;17:217-25.

Saha P, Kou JH. Effect of solubilizing excipients on permeation of poorly water-soluble compounds across Caco-2 cell monolayers. Eur J Pharm Biopharm 2000;50:403-11.

Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles

based drug delivery systems. Colloids and Surf B Biointerfaces


Nishiyama N, Bae Y, Miyata K, Fukushima S, Kataoka K. Smart polymeric

micelles for gene and drug delivery. Drug Discov Today Technol


Shegokar R, Muller RH. Nanocrystals: Industrially feasible multifunctional

formulation technology for poorly soluble actives. Int J Pharm


Muller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug

formulations in therapy: Rationale for development and what we can

expect for the future. Adv Drug Deliv Rev 2001;47:3-19.

Kohli K, Chopra S, Dhar D, Arora S, Khar RK. Self-emulsifying drug

delivery systems: An approach to enhance oral bioavailability. Drug

Discov Today 2010;15:958-65.

Company literature on ZOCOR® (Simvastatin) Tablets. NJ, USA: Merck

and Co., Inc; 2004. p. 1-12.

Nirogi R, Mudigonda K, Kandikere V. Chromatography–mass

spectrometry methods for the quantitation of statins in biological

samples. J Pharm Biomed Anal 2007;44:379-87.

Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G, et al. Development

of self-microemulsifying drug delivery systems (SMEDDS) for oral

bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm


Margulis-Goshen K, Magdassi S. Formation of simvastatin nanoparticles

from microemulsion. Nanomedicine 2009;5:274-81.

Mao Z, Ma L, Gao C, Shen J. Preformed microcapsules for loading and

sustained release of ciprofloxacin hydrochloride. J Control Release


Gupta H, Aqil M, Khar RK, Ali A, Bhatnagar A, Mittal G. Sparfloxacin-

loaded PLGA nanoparticles for sustained ocular drug delivery.

Nanomedicine 2010;6:324-33.

Bodmeier R, McGinity JW. The preparation and evaluation of drug

containing poly(dl-lactide) microspheres formed by the solvent

evaporation method. Pharm Res 1987;4:465-71.

Muthu MS, Rawat MK, Mishra A, Singh S. PLGA nanoparticle

formulations of risperidone: Preparation and neuropharmacological

evaluation. Nanomedicine 2009;5:323-33.

Budhian A, Siegel SJ, Winey KI. Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug content. Int J Pharm 2007;336:367-75.

Quintanar-Guerrero D, Fessi H, Allemann E, Doelker E. Influence of

stabilizing agents and preparative variables on the formation of poly

(D, L-lactic acid) nanoparticles by an emulsification-diffusion technique.

Int J Pharm 1996;143:133-41.

Mainardes RM, Evangelista RC. PLGA nanoparticles containing

praziquantel: Effect of formulation variables on size distribution. Int

J Pharm 2005;290:137-44.

Lourenco C, Teixeira M, Simees S, Gaspar R. Steric stabilization of

nanoparticles: Size and surface properties. Int J Pharm 1996;138:1-12.

Kohane DS, Tse JY, Yeo Y, Padera R, Shubina M, Langer R. Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum. J Biomed Mater Res A 2006;77:351-61.

Zhanga Z, Bua H, Gaoa Z, Huanga Y, Gaoa F, Li Y. The characteristics

and mechanism of simvastatin loaded lipid nanoparticles to increase

oral bioavailability in rats. Int J Pharm 2010;394:147-53.

Vogel HG, Vogel WH. Drug discovery and evaluation: Pharmacological

assays. Berlin: Springer-Verlag; 1997. p. 604-11.

Elson CE. Tropical oils: Nutritional and scientific issues. Crit Rev Food

Sci Nutr 1992;31:79-102.