Abstract
Ultrafine particles of paracetamol were produced by Rapid Expansion of Supercritical Solution (RESS). The experiments were conducted to investigate the effects of extraction temperature (313–353 K), extraction pressure (10–18 MPa), preexpansion temperature (363–403 K), and postexpansion temperature (273–323 K) on particles size and morphology of paracetamol particles. The characterization of the particles was determined by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Liquid Chromatography/Mass Spectrometry (LC-MS) analysis. The average particle size of the original paracetamol was 20.8 μm, while the average particle size of paracetamol after nanonization via the RESS process was 0.46 μm depending on the experimental conditions used. Moreover, the morphology of the processed particles changed to spherical and regular while the virgin particles of paracetamol were needle-shape and irregular. Response surface methodology (RSM) was used to optimize the process parameters. The extraction temperature, 347 K; extraction pressure, 12 MPa; preexpansion temperature, 403 K; and postexpansion temperature, 322 K was found to be the optimum conditions to achieve the minimum average particle size of paracetamol.
Highlights
Ultrafine materials, such as polymers, composites, ceramics, medicines, and metals, have opened new fields of application
Twenty-five experiments were performed to investigate the effects of the extraction temperature, extraction pressure, Table 1: Variables in Box-Behnken design
Levels used −1 0 1 313 333 353 10 14 18 363 383 403 273 298 323 preexpansion temperature, postexpansion temperature, and their interactions on the size of the paracetamol particles obtained from the Rapid Expansion of Supercritical Solution (RESS) process
Summary
Ultrafine materials, such as polymers, composites, ceramics, medicines, and metals, have opened new fields of application. A large number of medicines are insoluble or poorly soluble in water. The bioavailability of these medicines is limited by their insolubility. Dissolution rate is a function of the surface area of the particles and their solubility. The drawbacks of traditional micronization methods are application of high temperature and toxic solvents which can cause the degradation of the thermo-labile materials and residual toxic solvents. The Rapid Expansion of Supercritical Solution (RESS) is one of the supercritical fluid technologies which omit the problems of the conventional micronization methods to produce small particles with narrow particles size distribution (PSD). The high supersaturation ratios and the homogeneous conditions obtained due to the rapid expansion of a supercritical solution are the unique parameters of the RESS process. High supersaturation ratios cause the formation of small particles, and Journal of Nanomaterials
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