Preparation, characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent (SAS) process.

Chungnam National University, Daejeon, Republic of Korea.
European Journal of Pharmaceutics and Biopharmaceutics (Impact Factor: 3.83). 07/2008; 69(2):454-65. DOI: 10.1016/j.ejpb.2008.01.007
Source: PubMed

ABSTRACT In this work, amorphous atorvastatin calcium nanoparticles were successfully prepared using the supercritical antisolvent (SAS) process. The effect of process variables on particle size and distribution of atorvastatin calcium during particle formation was investigated. Solid state characterization, solubility, intrinsic dissolution, powder dissolution studies and pharmacokinetic study in rats were performed. Spherical particles with mean particle size ranging between 152 and 863 nm were obtained by varying process parameters such as precipitation vessel pressure and temperature, drug solution concentration and feed rate ratio of CO2/drug solution. XRD, TGA, FT-IR, FT-Raman, NMR and HPLC analysis indicated that atorvastatin calcium existed as anhydrous amorphous form and no degradation occurred after SAS process. When compared with crystalline form (unprocessed drug), amorphous atorvastatin calcium nanoparticles were of better performance in solubility and intrinsic dissolution rate, resulting in higher solubility and faster dissolution rate. In addition, intrinsic dissolution rate showed a good correlation with the solubility. The dissolution rates of amorphous atorvastatin calcium nanoparticles were highly increased in comparison with unprocessed drug by the enhancement of intrinsic dissolution rate and the reduction of particle size resulting in an increased specific surface area. The absorption of atorvastatin calcium after oral administration of amorphous atorvastatin calcium nanoparticles to rats was markedly increased.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to investigate the effect of particle size on the dissolution and oral absorption of pranlukast microsuspensions and nanosuspensions stabilized by hydroxypropylmethyl cellulose. Four pranlukast suspensions with different mean particle sizes (0.16, 0.89, 3.13, and 18.21μm) were prepared by various top-down processes such as jet milling, high pressure homogenization, and bead milling. The dissolution rate and oral absorption of pranlukast suspensions were significantly affected by the particle size. The in vivo pharmacokinetic parameters of pranlukast suspensions were increased with decreasing mean particle size of suspensions. Especially, the AUC0→24h and Cmax values of pranlukast nanosuspension with a particle size of 0.16μm were approximately 3.5- and 6.3-fold greater, respectively, than that of pranlukast microsuspension with a particle size of 18.21μm. Therefore, the preliminary results from our study suggest that a pranlukast nanosuspension with a mean particle size of about 0.16μm may have significant potential for clinical application.
    International journal of biological macromolecules 03/2014; · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clarithromycin (CLM) is a member of macrolide family with broad spectrum antibiotic activity. It is practically insoluble in water and its poor solubility is pH dependent. In this study, series of nanosuspensions containing CLM and stabilizer such as HPMC, NaCMC, polysorbate 80, poloxamer 188 and polyvinyl alcohol in various ratios were prepared using sonoprecipitation method. Briefly, CLM was dissolved in acid solution and the pH of solution was raised under sonication and the effects of different stabilizers on particle size of nanoparticles were evaluated. Characterization of nanoparticles in terms of size, polydispersity index, zeta potential, differential scanning calorimetery and dissolution studies was performed. Antimicrobial activity of CLM nanosuspension was compared with coarse powder by using an agar well diffusion method. The results showed that HPMC was more efficient in size reduction of particles and presence of HPMC E5 with ratio of 3:5 to CLM in formulation led to develop the stable nanosuspension with particle size of 340 nm. The obtained nanosuspension successfully showed enhanced dissolution rate and antimicrobial activity.
    Iranian journal of pharmaceutical research (IJPR) 01/2014; 13(3):809-818. · 0.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which cat-alyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Sim-vastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dis-solution rate and extend drug absorption. As carriers for solid dispersion, Gelucire ® 44/14 and Gelucire ® 50/13 are semi-solid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween ® 80 and distilled water. The structural behaviors of the raw materials and
    08/2011; 41:239-247.


Available from