Production of Luteolin/Biopolymer Microspheres by Supercritical Assisted Atomization

Abstract

Supercritical assisted atomization (SAA) was used to produce coprecipitated submicroparticles of luteolin (LUT)/poly(vinylpyrrolidone) (PVP) for pharmaceutical applications. LUT has antioxidant, antiinflammatory, and antitumoral properties but is poorly water-soluble, whereas PVP is highly water-soluble. This polymer can be used to protect the active molecule and to improve its bioavailability. Different LUT/PVP weight ratios were selected ranging between 1:4 and 1:8. SAA produced partly collapsed spherical particles with controlled particle size and mean diameters ranging between 0.22 and 0.33 μm. UV-vis analyses revealed very high loading efficiency of LUT in SAA particles (99-100%). The powders are amorphous, whereas the untreated material shows crystalline patterns. Fourier transform infrared revealed that hydrogen bonds were created between the drug and polymer. Drug-release analysis indicated that the supercritical processing was successful: the LUT dissolution rate in a phosphate-buffered saline solution was up to 9 times faster compared to that of an unprocessed drug

The Use of Poly(N-vinyl pyrrolidone) in the Delivery of Drugs: A Review

“…Moreover, PVP is used as a masking agent for odors/flavors, as well as a stabilizing or protective agent for the active compound, avoiding its oxidation and deactivation. PVP was widely used to obtain both microcapsules [19,40] and microspheres [2,21,39,42,[46][47][48][49][50][51][52][53][54][55][56]. A core-shell structure characterizes the microcapsules ( Figure 1a); generally, the core material contains the active compound, whereas the wall material consists of the polymeric carrier (PVP or blends).…”

“…To overcome these limits, supercritical carbon dioxide (CO 2 ) assisted technologies were proposed to produce drug-loaded PVP microparticles, mainly Supercritical Assisted Atomization (SAA) [46][47][48][49] and Supercritical AntiSolvent (SAS) process [20,21,[41][42][43][44][45][50][51][52][53][54][55][56][74][75][76]. In detail, the CO 2 acts as a cosolute in the SAA process and as an antisolvent in the SAS process.…”

“…Micrometric and sub-micrometric composite particles with an amorphous structure can be obtained by properly selecting the operating conditions. This allowed significantly increasing the dissolution rate of various active compounds belonging to different categories, such as antioxidants [41,[46][47][48][49]53,54,56,74], non-steroidal anti-inflammatory drugs (NSAIDs) [20,51,55,76], vitamins [42,52], and corticosteroids [21]. Indeed, the mild operating conditions used in supercritical CO 2 -based technologies even allow the processing of thermosensitive compounds without degradation or deactivation, e.g., preserving the antioxidant activity of the active material [48,49,56].…”

“…In contrast, the increase of the concentration of solutes in the injected liquid solution leads to an increase in the particle dimensions [78]. Instead, regarding the SAA process, the gas-to-liquid ratio (GLR; i.e., the weight ratio between CO 2 and the liquid solution) strongly influences the particle morphology and dimensions [46][47][48][49]; indeed, by increasing the GLR, the particle dimensions decrease and the particle size distribution shrinks.…”

Antioxidants entrapment in polycaprolactone microparticles using supercritical assisted injection in a liquid antisolvent

“…A valid alternative to conventional micronization techniques is represented by supercritical fluid assisted processes, which are widely used to entrap drugs in polymeric matrices ( Di Capua et al, 2017a , b ; Gimenez-Rota et al, 2019 ; Tirado et al, 2019 ). Ozkan et al (2019) studied the micronization of two flavonoids, quercetin and rutin, and their coprecipitation with polyvinylpyrrolidone (PVP) using the supercritical antisolvent process (SAS).…”