Micronization of cilostazol using supercritical antisolvent (SAS) process: Effect of process parameters

Kim, Min Soo; Lee, Sibeum; Park, Jeong Sook; Woo, Jong Soo; Hwang, Sung Joo

doi:10.1016/j.powtec.2007.02.029

Cited by 100 publications

(69 citation statements)

References 30 publications

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“…This finding agrees with a previous report showing that an increased drug concentration in organic solvent produced a larger mean particle size in the SAS process. 9,25) These results can be explained in terms of nucleation and growth processes. When dilute solutions are injected, it takes longer to achieve saturation and precipitation; thus, nucleation is the prevailing mechanism, and smaller particles are formed.…”

Section: Effect Of Drug Solution Concentrationmentioning

confidence: 90%

“…[4][5][6][7][8][9] Previously, we investigated the effect of SAS process parameters such as the pressure, temperature, and feed rate ratio of CO 2 /drug solution on the particle formation of atorvastatin calcium using methanol as a solvent.…”

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confidence: 99%

“…2,3) Many researchers have been studied that the morphology, crystallinity, particle size and particle size distribution can be controlled through the changing of various process conditions such as temperature, pressure, solvent, drug solution concentration, solution to antisolvent flow rate ratio, and the rate of mass transfer in SAS process. [4][5][6][7][8][9] Previously, we investigated the effect of SAS process parameters such as the pressure, temperature, and feed rate ratio of CO 2 /drug solution on the particle formation of atorvastatin calcium using methanol as a solvent. 10) In addition, we reported the usefulness of the amorphous nanoparticles as a method of enhancing the supersaturation, dissolution, and absorption properties of atorvastatin.…”

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Effect of Solvent Type on the Nanoparticle Formation of Atorvastatin Calcium by the Supercritical Antisolvent Process

et al. 2012

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The aims of this study were to identify how the solvent selection affects particle formation and to examine the effect of the initial drug solution concentration on mean particle size and particle size distribution in the supercritical antisolvent (SAS) process. Amorphous atorvastatin calcium was precipitated from seven different solvents using the SAS process. Particles with mean particle size ranging between 62.6 and 1493.7 nm were obtained by varying organic solvent type and solution concentration. By changing the solvent, we observed large variations in particle size and particle size distribution, accompanied by different particle morphologies. Particles obtained from acetone and tetrahydrofuran (THF) were compact and spherical fine particles, whereas those from N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) were agglomerated, with rough surfaces and relatively larger particle sizes. Interestingly, the mean particle size of atorvastatin calcium increased with an increase in the boiling point of the organic solvent used. Thus, for atorvastatin particle formation via the SAS process, particle size was determined mainly by evaporation of the organic solvent into the antisolvent phase. In addition, the mean particle size was increased with increasing drug solution concentration. In this study, from the aspects of particle size and solvent toxicity, acetone was the better organic solvent for controlling nanoparticle formation of atorvastatin calcium.Key words atorvastatin; nanoparticle; supercritical antisolvent; amorphous A new approach in particle engineering developed to obtain micro/nanoparticles with peculiar characteristics is represented by the supercritical fluid technology.1) Among the several types of supercritical fluid processes, supercritical antisolvent (SAS) process have some advantages such as easy handling of difficult-to-comminute materials, use of a nontoxic medium, and a mild operating temperature may provide ideal conditions for the processing of pharmaceutical compounds. Moreover, fast diffusion of supercritical antisolvent into the liquid solvent produces the supersaturation of the solute and its precipitation in micronized particles down to particle diameters, and control of the particle size distribution is also possible.2,3) Many researchers have been studied that the morphology, crystallinity, particle size and particle size distribution can be controlled through the changing of various process conditions such as temperature, pressure, solvent, drug solution concentration, solution to antisolvent flow rate ratio, and the rate of mass transfer in SAS process. [4][5][6][7][8][9] Previously, we investigated the effect of SAS process parameters such as the pressure, temperature, and feed rate ratio of CO 2 /drug solution on the particle formation of atorvastatin calcium using methanol as a solvent.10) In addition, we reported the usefulness of the amorphous nanoparticles as a method of enhancing the supersaturation, dissolution, and absorption properties of atorvastatin.11) However...

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Section: Effect Of Drug Solution Concentrationmentioning

confidence: 90%

mentioning

confidence: 99%

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confidence: 99%

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Effect of Solvent Type on the Nanoparticle Formation of Atorvastatin Calcium by the Supercritical Antisolvent Process

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“…5,28,32,45 In a subcritical condition, increasing the pressure produces smaller particles. 32,37,72 Other authors found that pressure variations do not exert a great effect on the mean particle size in pressures higher than asymptotic volume expansion. 8,41 Increasing the temperature reduces the solubility and thus enhances the maximum supersaturation, so that smaller particles are obtained.…”

Section: Effects Of Pressure and Temperaturementioning

confidence: 99%

Application of supercritical antisolvent method in drug encapsulation: a review

Kalani¹,

Yunus²

2011

IJN

115

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The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer), nozzle geometry, CO 2 flow rate, and the liquid phase flow rate on particle size and its distribution.

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“…[3][4][5] Several studies have been carried out to investigate methods for increasing the dissolution rate of drugs by decreasing particle size (eg, by developing nanoparticles and microparticles). 6,7 However, handling micronized drugs is often problematic because extremely small particles tend to agglomerate, requiring additional stabilization.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

Ho¹,

Cho²,

Kim³

et al. 2012

IJN

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Background: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO 2 . Methods: Fenofibrate was loaded onto Neusilin ® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO 2 . For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated. Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO 2 facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO 2 were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate. Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO 2 for improving the bioavailability of fenofibrate.

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Micronization of cilostazol using supercritical antisolvent (SAS) process: Effect of process parameters

Cited by 100 publications

References 30 publications

Effect of Solvent Type on the Nanoparticle Formation of Atorvastatin Calcium by the Supercritical Antisolvent Process

Effect of Solvent Type on the Nanoparticle Formation of Atorvastatin Calcium by the Supercritical Antisolvent Process

Application of supercritical antisolvent method in drug encapsulation: a review

Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

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