Preparation and in-vitro Evaluation of Poly--Caprolactone Nanoparticles Containing Atorvastation Calcium

  • Iman Saad Ahmed Cairo University; University of Sharjah
  • Rania El Hosary
  • Samia Shalaby
  • Samia Nour


Preparation and evaluation of poly-e-caprolactone nanoparticles containing atorvastatin calcium (AC), a drug with poor solubility and poor bioavailability, is presented. The drug loaded nanoparticles were prepared by solvent displacement method using different experimental conditions.  The influence of different formulation variables, such as type and concentration of stabilizers in the aqueous phase, concentration of polymer and surfactant in the organic phase, addition of an anti-oxidant, pH of the aqueous phase and others, on particle size, drug entrapment efficiency, in-vitro drug release along with other physico-chemical properties of the nanoparticles was investigated using several full factorial designs. The optimized AC nanoparticles showed an average particle size of less than 200 nm, a drug loading capacity of more than 70% and released the drug in a controlled fashion over 24 hour. Transmission electron microscope (TEM) revealed that the prepared AC nanoparticles were nearly spherical. Short-term stability results of selected formulae were satisfactory.



Anwar M., Warsi M.H., Mallick N., Akhter S., Gahoi S., Jain G.K., Talegaonkar S., Ahmad F.J., Khar R.K. (2011) Enhanced bioavailability of nano-sized chitosan-atorvastatin conjugate after oral administration to rats. Eur. J. Pharm. Sci., 44, 241249.

Beck-Broichsitter M., Rytting E., Lebhardt T., Wang X., Kissel, T. (2010) Preparation of nanoparticles by solvent displacement for drug delivery: A shift in the “ouzo region†upon drug loading. Eur. J. Pharm. Sci., 41, 244253.

Calvo P., Vila-Jato J.L., Alonso M.J. (1996) Comparative in vitro evaluation of several colloidal systems, nanoparticles, nanocapsules and nanoemulsions, as ocular drug carrier. J. Pharm. Sci., 85, 530536.

Chacón M., Molpeceres J., Berges L., Guzmán M., Aberturas M.R. (1999) Stability and freeze-drying of cyclosporine loaded poly (D,L lactide-glycolide) carriers. Eur. J. Pharm. Sci., 8, 99107.

Chen Y., Zhang G.G., Neilly J., Marsh K., Mawhinney D., Sanzgiri Y.D. (2004) Enhancing the bioavailability of ABT-963 using solid dispersion containing pluronic F-68. Int. J. Pharm., 286, 6980.

Chorny M., Fishbein I., Danenberg H.D., Golomb G. (2000) Lipophilic drug loaded nanospheres prepared by nanoprecipitation: effect of formulation variables on size, drug recovery and release kinetics. J. Control. Release, 83, 389400.

Constantinides P.P., Han J., Davis S.S. (2006) Advances in the use of tocols as drug delivery vehicles. Pharm. Res., 23, 243255.

Date A.A., Desai N., Dixit R., Nagarsenker M. (2010) Self-nanoemulsifying drug delivery systems: formulations insights, applications and advances. Nanomedicine, 5, 15951616.

Feng S. & Huang, G. (2001) Effects of emulsiï¬ers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymer. J. Control. Release, 71, 5369.

Fontana G., Pitarresi G., Tomarchio V., Carlisi B., San Biagio P.L. (1998) Preparation, characterization and in vitro antimicrobial activity of ampicillin-loaded polyethylcyanoacrylate nanoparticles. Biomaterials, 19, 10091017.

Ghosh I., Bose S., Vippagunta R., Harmon F. (2011) Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int. J. Pharm., 409, 260268.

Govender T., Stolnik S., Garnett M.C., Illum L., Davis S.S. (1999) PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J. Control. Release, 57, 171185.

Graca M., Bongaerts J.H., Stokes J.R., Granick S. (2007) Friction and adsorption of aqueous polyoxyethylene (Tween) surfactants at hydrophobic surfaces. J. Colloid. Interface Sci., 315, 662670.

Han H.K. & Choi H.K. (2007) Improved absorption of meloxicam via salt formation with ethanolamines. Eur. J. Pharm. Biopharm., 65, 99103.

International Conference of Harmonization. Q2 (R1) Validation of Analytical Procedures: Text and Methodology, 2005.

Khan F., Islam M.S., Roni M.A., Jalil R.U. (2012) Systematic development of self-emulsifying drug delivery systems of atorvastatin with improved bioavailability potential. Sci. Pharm., 80, 10271043.

Korsmeyer R.W. & Peppas N.A. (1983) Modeling drug release from swellable systems. Proc. Symp. Control. Release Bioact. Mater., 10, 141144.

Lai S.K., Wang Y.Y., Hanes J. (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Int. J. Pharm., 6, 158171.

Law M.R., Wald N.J., Rudnicka A.R. (2003) Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. Br. Med. J., 326, 14231427.

Lennernas H. (2003) Clinical pharmacokinetics of atorvastatin. Clin. Pharmacokinet., 42, 11411160.

Lin W.J. & Huang, L.I. (2001) Fabrication of porous poly(ï¥-caprolactone) microparticles for protein release. J. Microencapsul., 18, 577–584.

Mantri S.K., Pashikanti S., Murthy K.V. (2012) Development and characterization of self-nanoemulsifying drug delivery systems (SNEDDS) of atorvastatin calcium. Curr. Drug Deliv., 9, 182-196.

Mishra, B., Patel, B.B., and Tiwari, S. (2010) Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery. Nanomedicine, 6, 924.

Molpeceres J., Guzman M., Aberturas M.R., Chacon M., Berges L. (1996) Application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement. J. Pharm. Sci., 85, 206213.

Mora-Huertas C.E., Fessi H., Elaissari A. (2011) Influence of process and formulation parameters on the formation of submicron particles by solvent displacement and emulsification–diffusion methods critical comparison. Adv. Colloid. Interface Sci., 163, 90122.

Murakami H., Kawashima Y., Niwa T., Hino T., Takeuchi H., Kobyashi M. (1997) Influence of the degrees of hydrolyzation and polymerization of poly(vinyl alcohol) on the preparation and properties of poly(D,L-lactide-co-glycolide) nanoparticle. Int. J. Pharm., 149, 4349.

Palla B.J. & Shah D.O. (2002) Stabilization of high ionic strength slurries using surfactant mixtures: Molecular factors that determine optimal stability. J. Colloid. Interface Sci., 256, 143152.

Park M.J., Ren S., Lee B.J. (2007) In vitro and in vivo comparative study of itraconazole bioavailability when formulated in highly soluble self-emulsifying system and in solid dispersion. J. Biopharm. Drug Dispos., 28,199207.

Peï‚¢rez M.H., Zinutti C., Lamprecht A., Ubrich N., Astier A., Hoffman M., Bodmeier R., Maincent, P. (2000) The preparation and evaluation of poly(ï¥-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug. J. Control. Release, 65, 429438.

Peltonen L., Aitta J., Hyvoenen S., Karjalainen M., Hirvonen, J. (2004) Improved entrapment efficiency of hydrophilic drug substance during nanoprecipitation of poly L-lactide nanoparticles. AAPS PharmSciTech., 5, E16.

Scholes P.D., Coombes A.G., Illum L., Davis S.S., Watts J.F., Ustariz C., Vert M., Davies M.C. (1999) Detection and determination of surface levels of poloxamer and PVA surfactant on biodegradable nanospheres using SSIMS and XPS. J. Control. Release, 59, 261–278.

Shah R.P., Kumar V., Singh S. (2008) Liquid chromatography/mass spectrometric studies on atorvastatin and its stress degradation products. Rapid Commun. Mass. Spectrom., 22, 613622.

Sinha V.R., Bansal K., Kaushik R., Kumria R., Trehan A. (2004) Poly-ï¥caprolactone microspheres and nanospheres: an overview. Int. J. Pharm., 278, 123.

Soppimath K.S., Aminabhavi T.M., Kulkarini A.R., Rudziniski W.E. (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J. Control. Release, 70, 120.

Tsukada Y., Hara K., Bando Y., Huang C.C., Kousaka Y., Kawashima Y., Morishita R., Tsujimoto H. (2009) Particle size control of poly (DL-lactide-co-glycolide) nanospheres for sterile applications. Int. J. Pharm., 370, 196201.

Van Eerdenbrugh B., Van den Mooter G., Augustijins P. (2008) Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. Int. J. Pharm., 364, 6475.

Witschi C. & Doelker, E. (1998) Influence of the microencapsulation method and peptide loading on polylactic acid and polylactic-co-glycolic acid degradation during in vitro testing. J. Control. Release, 51, 327341.

Wu L., Zhang J.,Watanabe W. (2011) Physical and chemical stability of drug nanoparticles. Adv. Drug Deliv. Rev., 63, 456469.

Wu X., Whitfield L.R., Stewart B.H. (2000) Atorvastatin transport in the Caco-2 Cell Model: contributions of P-glycoprotein and the proton-monocarboxylic acid cotransporter. Pharm. Res., 17, 209215.

Zhang H.X, Wanga J.X., Zhanga Z.B., Lea Y., Shenb Z.G., Chenb J.F. (2009) Micronization of atorvastatin calcium by antisolvent precipitation process. Int. J. Pharm., 374, 106113.

How to Cite
Ahmed, I., El Hosary, R., Shalaby, S., & Nour, S. (2014). Preparation and in-vitro Evaluation of Poly--Caprolactone Nanoparticles Containing Atorvastation Calcium. Journal of Research and Opinion, 4(1). Retrieved from