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Pharmaceutics
Special Issues
Supercritical Fluid and Pharmaceutical Applications
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Supercritical Fluid and Pharmaceutical Applications

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 22760

Special Issue Editor

Prof. Dr. Iolanda De Marco

E-Mail Website
Guest Editor
Industrial Engineering Department, University of Salerno, Via Giovanni Paolo II, 132, I-84084 Fisciano, SA, Italy
Interests: polymer/active principle composites; drug delivery; supercritical carbon dioxide; microparticles and nanoparticles precipitation; biopolymer aerogels; polymer/drug coprecipitation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Supercritical fluids (SCFs) based techniques have been proposed as a green alternative to conventional processes, thanks to SCFs outstanding properties, such as liquid-like densities with gas-like transport properties that can be tuned varying pressure and temperature. Carbon dioxide is the preferred fluid due to its mild critical temperature (31.1◦C), low critical pressure (7.38 MPa) and inertness. Depending on the role played by the supercritical carbon dioxide, different processes have been successfully applied in the pharmaceutical field, in order to obtain microparticles and nanoparticles of active principles, coprecipitate drugs with biocompatible polymers, generate membranes and aerogels for pharmaceutical applications, impregnate drugs in porous structures, or produce solid lipid nanoparticles or liposomes.

The aim of this Special Issue is to collect research and review papers on different supercritical carbon dioxide applications in the pharmaceutical field. Contributions dealing with the processing of active principles and the attainment of polymer/drug composites in form of micro and nanoparticles, foams, membranes, aerogels or liposomes for drug delivery are welcome.

Prof. Dr. Iolanda De Marco
Guest Editor

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Keywords

  • Supercritical carbon dioxide
  • Microparticles and nanoparticles processing
  • Membranes, aerogels and foams
  • Liposomes and solid lipid nanoparticles
  • Targeted and controlled drug delivery
  • Supercritical Impregnation

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Published Papers (5 papers)

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Research

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11 pages, 2650 KiB  
Article
Application of Box–Behnken Design to Investigate the Effect of Process Parameters on the Microparticle Production of Ethenzamide through the Rapid Expansion of the Supercritical Solutions Process
by Yung-Tai Hsu and Chie-Shaan Su
Pharmaceutics 2020, 12(1), 42; https://doi.org/10.3390/pharmaceutics12010042 - 3 Jan 2020
Cited by 10 | Viewed by 2614
Abstract
In this study, the rapid expansion of the supercritical solutions (RESS) process was used to produce microparticles of a commonly used anti-inflammatory drug, ethenzamide. The effects of process parameters in RESS including the extraction temperature, pre-expansion temperature, and post-expansion temperature were investigated using [...] Read more.
In this study, the rapid expansion of the supercritical solutions (RESS) process was used to produce microparticles of a commonly used anti-inflammatory drug, ethenzamide. The effects of process parameters in RESS including the extraction temperature, pre-expansion temperature, and post-expansion temperature were investigated using the Box–Behnken design. According to the results of the analysis of variance (ANOVA), the effect of pre-expansion temperature is the most significant parameter on the mean size of RESS-produced ethenzamide. A higher pre-expansion temperature benefits the production of smaller crystals. In addition, a quadratic effect of the post-expansion temperature was also identified. Through RESS, ethenzamide microparticles with a mean size of 1.6 μm were successfully produced. The solid-state properties including the crystal habit, crystal form, thermal behavior, and spectrometric property were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectrometer (FTIR), differential scanning calorimeter (DSC), and powder X-ray diffraction (PXRD). These analytical results show that the rod-like crystals were generated through RESS, and the crystal form, thermal behavior, and spectrometric property of RESS-produced crystals are consistent with the unprocessed ethenzamide. Full article
(This article belongs to the Special Issue Supercritical Fluid and Pharmaceutical Applications)
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17 pages, 4973 KiB  
Article
PCL/Mesoglycan Devices Obtained by Supercritical Foaming and Impregnation
by Paola Franco, Raffaella Belvedere, Emanuela Pessolano, Sara Liparoti, Roberto Pantani, Antonello Petrella and Iolanda De Marco
Pharmaceutics 2019, 11(12), 631; https://doi.org/10.3390/pharmaceutics11120631 - 26 Nov 2019
Cited by 23 | Viewed by 3314
Abstract
In this work, a one-shot process for the simultaneous foaming of polycaprolactone (PCL) and impregnation of mesoglycan (MSG) into the porous structure was successfully attempted. Supercritical carbon dioxide plays the role of the foaming agent with respect to PCL and of the solvent [...] Read more.
In this work, a one-shot process for the simultaneous foaming of polycaprolactone (PCL) and impregnation of mesoglycan (MSG) into the porous structure was successfully attempted. Supercritical carbon dioxide plays the role of the foaming agent with respect to PCL and of the solvent with respect to MSG. The main objective is to produce an innovative topical device for application on skin lesions, promoting prolonged pro-resolving effects. The obtained device offers a protective barrier to ensure a favorable and sterilized environment for the wound healing process. The impregnation kinetics revealed that a pressure of 17 MPa, a temperature of 35 °C, and a time of impregnation of 24 h assured a proper foaming of PCL in addition to the impregnation of the maximum amount of MSG; i.e., 0.22 mgMSG/mgPCL. After a preliminary study conducted on PCL granules used as brought, the MSG impregnation was performed at the optimized process conditions also on a PCL film, produced by compression molding, with the final goal of producing medical patches. Comparing the dissolution profiles in phosphate buffered saline solution (PBS) of pure MSG and MSG impregnated on foamed PCL, it was demonstrated that the release of MSG was significantly prolonged up to 70 times. Next, we performed functional assays of in vitro wound healing, cell invasion, and angiogenesis to evaluate the biological effects of the PCL-derived MSG. Interestingly, we found the ability of this composite system to promote the activation of human keratinocytes, fibroblasts, and endothelial cells, as the main actors of tissue regeneration, confirming what we previously showed for the MSG alone. Full article
(This article belongs to the Special Issue Supercritical Fluid and Pharmaceutical Applications)
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18 pages, 3471 KiB  
Article
Preparation, Characterization, and In Vivo Pharmacokinetic Study of the Supercritical Fluid-Processed Liposomal Amphotericin B
by Chang-baek Lim, Sharif Md Abuzar, Pankaj Ranjan Karn, Wonkyung Cho, Hee Jun Park, Cheong-Weon Cho and Sung-Joo Hwang
Pharmaceutics 2019, 11(11), 589; https://doi.org/10.3390/pharmaceutics11110589 - 8 Nov 2019
Cited by 24 | Viewed by 4984
Abstract
Here, we aimed to prepare and optimize liposomal amphotericin B (AmB) while using the supercritical fluid of carbon dioxide (SCF-CO2) method and investigate the characteristics and pharmacokinetics of the SCF-CO2-processed liposomal AmB. Liposomes containing phospholipids, ascorbic acid (vit C), [...] Read more.
Here, we aimed to prepare and optimize liposomal amphotericin B (AmB) while using the supercritical fluid of carbon dioxide (SCF-CO2) method and investigate the characteristics and pharmacokinetics of the SCF-CO2-processed liposomal AmB. Liposomes containing phospholipids, ascorbic acid (vit C), and cholesterol were prepared by the SCF-CO2 method at an optimized pressure and temperature; conventional liposomes were also prepared using the thin film hydration method and then compared with the SCF-CO2-processed-liposomes. The optimized formulation was evaluated by in vitro hemolysis tests on rat erythrocytes and in vivo pharmacokinetics after intravenous administration to Sprague-Dawley rats and compared with a marketed AmB micellar formulation, Fungizone®, and a liposomal formulation, AmBisome®. The results of the characterization studies demonstrated that the SCF-CO2-processed-liposomes were spherical particles with an average particle size of 137 nm (after homogenization) and drug encapsulation efficiency (EE) was about 90%. After freeze-drying, mean particle size, EE, and zeta potential were not significantly changed. The stability study of the liposomes showed that liposomal AmB that was prepared by the SCF method was stable over time. In vivo pharmacokinetics revealed that the SCF-CO2-processed-liposomes were bioequivalent to AmBisome®; the hemolytic test depicted less hematotoxicity than Fungizone®. Therefore, this method could serve as a potential alternative for preparing liposomal AmB for industrial applications. Full article
(This article belongs to the Special Issue Supercritical Fluid and Pharmaceutical Applications)
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14 pages, 3088 KiB  
Article
Supercritical Solvent Impregnation of Different Drugs in Mesoporous Nanostructured ZnO
by Mauro Banchero, Sara S. Y. Mohamed, Federica Leone, Francesca Lopez, Silvia Ronchetti, Luigi Manna and Barbara Onida
Pharmaceutics 2019, 11(7), 340; https://doi.org/10.3390/pharmaceutics11070340 - 15 Jul 2019
Cited by 19 | Viewed by 3358
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Supercritical Fluid and Pharmaceutical Applications)
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Review

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34 pages, 1026 KiB  
Review
Using Supercritical Fluid Technology as a Green Alternative During the Preparation of Drug Delivery Systems
by Paroma Chakravarty, Amin Famili, Karthik Nagapudi and Mohammad A. Al-Sayah
Pharmaceutics 2019, 11(12), 629; https://doi.org/10.3390/pharmaceutics11120629 - 25 Nov 2019
Cited by 101 | Viewed by 7806
Abstract
Micro- and nano-carrier formulations have been developed as drug delivery systems for active pharmaceutical ingredients (APIs) that suffer from poor physico-chemical, pharmacokinetic, and pharmacodynamic properties. Encapsulating the APIs in such systems can help improve their stability by protecting them from harsh conditions such [...] Read more.
Micro- and nano-carrier formulations have been developed as drug delivery systems for active pharmaceutical ingredients (APIs) that suffer from poor physico-chemical, pharmacokinetic, and pharmacodynamic properties. Encapsulating the APIs in such systems can help improve their stability by protecting them from harsh conditions such as light, oxygen, temperature, pH, enzymes, and others. Consequently, the API’s dissolution rate and bioavailability are tremendously improved. Conventional techniques used in the production of these drug carrier formulations have several drawbacks, including thermal and chemical stability of the APIs, excessive use of organic solvents, high residual solvent levels, difficult particle size control and distributions, drug loading-related challenges, and time and energy consumption. This review illustrates how supercritical fluid (SCF) technologies can be superior in controlling the morphology of API particles and in the production of drug carriers due to SCF’s non-toxic, inert, economical, and environmentally friendly properties. The SCF’s advantages, benefits, and various preparation methods are discussed. Drug carrier formulations discussed in this review include microparticles, nanoparticles, polymeric membranes, aerogels, microporous foams, solid lipid nanoparticles, and liposomes. Full article
(This article belongs to the Special Issue Supercritical Fluid and Pharmaceutical Applications)
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