Abstract
Supercritical solvent impregnation (SSI) is a green unconventional technique for preparing amorphous drug formulations. A mesoporous nanostructured ZnO (mesoNsZnO) carrier with 8-nm pores, spherical-nanoparticle morphology, and an SSA of 75 m2/g has been synthesized and, for the first time, subjected to SSI with poorly water-soluble drugs. Ibuprofen (IBU), clotrimazole (CTZ), and hydrocortisone (HC) were selected as highly, moderately, and poorly CO2-soluble drugs. Powder X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, nitrogen adsorption analysis, and ethanol extraction coupled with ultraviolet spectroscopy were employed to characterize the samples and quantify drug loading. Successful results were obtained with IBU and CTZ while HC loading was negligible, which could be related to different solubilities in CO2, drug size, and polarity. Successful SSI resulted in amorphous multilayer confinement of the drug. The mesoNsZnO-IBU system showed double drug loading than the mesoNsZnO-CTZ one, with a maximum uptake of 0.24 g/g. Variation of contact time during SSI of the mesoNsZnO-IBU system showed that drug loading triplicated between 3 and 8 h with an additional 30% increment between 8 h and 24 h. SSI did not affect the mesoNsZnO structure, and the presence of the adsorbed drug reduced the chemisorption of CO2 on the carrier surface.
Highlights
Supercritical fluid technology can be considered one of the most effective alternatives to conventional manufacturing processes of pharmaceuticals especially as far as drug delivery and biomedical applications are concerned [1,2,3]
A mesoporous Zinc oxide (ZnO) carrier with uniform pores of 8 nm size, a spherical-nanoparticle morphology, and an specific surface area (SSA) of 75 m2/g has been subjected to Supercritical solvent impregnation (SSI) to achieve incorporation of poorly water-soluble drugs for the first time
The drug-drug molecular interactions should not be too strong to prevent those between the drug and the porous matrix to occur during the impregnation process
Summary
Supercritical fluid technology can be considered one of the most effective alternatives to conventional manufacturing processes of pharmaceuticals especially as far as drug delivery and biomedical applications are concerned [1,2,3]. Supercritical solvent impregnation (SSI) is among the techniques that can be used to prepare drug delivery vehicles by means of scCO2 [1,2]. It consists of dissolving the drug in the supercritical medium, which is brought in contact with the adsorbent material. Depending on the drug-drug and drug-matrix interactions, the drug can be confined in the porous structure in its amorphous form [4] This has gained a great deal of attention in pharmaceutical science, since amorphous drug formulations may result in significant increase of the solubility and dissolution rate of poorly water-soluble drugs [10]
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