Low drug bioavailability, which is mostly a result of poor aqueous drug solubilities and of inadequate drug dissolution rates, is one of the most significant challenges that pharmaceutical companies ...are currently facing, since this may limit the therapeutic efficacy of marketed drugs, or even result in the discard of potential highly effective drug candidates during developmental stages. Two of the main approaches that have been implemented in recent years to overcome poor drug solubility/dissolution issues have frequently involved drug particle size reduction (i.e., micronization/nanonization) and/or the modification of some of the physicochemical and structural properties of poorly water soluble drugs. A large number of particle engineering methodologies have been developed, tested, and applied in the synthesis and control of particle size/particle-size distributions, crystallinities, and polymorphic purities of drug micro- and nano-particles/crystals. In recent years pharmaceutical processing using supercritical fluids (SCF), in general, and supercritical carbon dioxide (scCO2), in particular, have attracted a great attention from the pharmaceutical industry. This is mostly due to the several well-known advantageous technical features of these processes, as well as to other increasingly important subjects for the pharmaceutical industry, namely their “green”, sustainable, safe and “environmentally-friendly” intrinsic characteristics.
In this work, it is presented a comprehensive state-of-the-art review on scCO2-based processes focused on the formation and on the control of the physicochemical, structural and morphological properties of amorphous/crystalline pure drug nanoparticles. It is presented and discussed the most relevant scCO2, scCO2-based fluids and drug physicochemical properties that are pertinent for the development of successful pharmaceutical products, namely those that are critical in the selection of an adequate scCO2-based method to produce pure drug nanoparticles/nanocrystals. scCO2-based nanoparticle formation methodologies are classified in three main families, and in terms of the most important role played by scCO2 in particle formation processes: as a solvent; as an antisolvent or a co-antisolvent; and as a “high mobility” additive (a solute, a co-solute, or a co-solvent). Specific particle formation methods belonging to each one of these families are presented, discussed and compared. Some selected amorphous/crystalline drug nanoparticles that were prepared by these methods are compiled and presented, namely those studied in the last 10–15 years. A special emphasis is given to the formation of drug cocrystals. It is also discussed the fundamental knowledge and the main mechanisms in which the scCO2-based particle formation methods rely on, as well as the current status and urgent needs in terms of reliable experimental data and of robust modeling approaches. Other addressed and discussed topics include the currently available and the most adequate physicochemical, morphological and biological characterization methods required for pure drug nanoparticles/nanocrystals, some of the current nanometrology and regulatory issues associated to the use of these methods, as well as some scale-up, post-processing and pharmaceutical regulatory subjects related to the industrial implementation of these scCO2-based processes. Finally, it is also discussed the current status of these techniques, as well as their future major perspectives and opportunities for industrial implementation in the upcoming years.
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Net-zero emissions energy systems Davis, Steven J; Lewis, Nathan S; Shaner, Matthew ...
Science (American Association for the Advancement of Science),
2018-Jun-29, 2018-06-29, 20180629, Volume:
360, Issue:
6396
Journal Article
Peer reviewed
Open access
Some energy services and industrial processes-such as long-distance freight transport, air travel, highly reliable electricity, and steel and cement manufacturing-are particularly difficult to ...provide without adding carbon dioxide (CO
) to the atmosphere. Rapidly growing demand for these services, combined with long lead times for technology development and long lifetimes of energy infrastructure, make decarbonization of these services both essential and urgent. We examine barriers and opportunities associated with these difficult-to-decarbonize services and processes, including possible technological solutions and research and development priorities. A range of existing technologies could meet future demands for these services and processes without net addition of CO
to the atmosphere, but their use may depend on a combination of cost reductions via research and innovation, as well as coordinated deployment and integration of operations across currently discrete energy industries.
Non-thermal food processing is configured as an interesting alternative for the food industry due to the increased nutrient retention and minimal sensory changes in processed products.
The aim of ...this review is to address the potential of supercritical carbon dioxide technology, emphasizing milk and dairy processing, including the historical aspects, main advantages, microbial inactivation mechanisms, as well as effects in some quality parameters of dairy products.
The use of supercritical carbon dioxide technology (SC-CO2) presents great potential application in dairy processing, since it is effective to reduce microbial load when compared to the pasteurization process, thus obtaining a product with greater shelf life and better organoleptic properties with minimal and sometimes positive changes in the intrinsic quality parameters.
•Supercritical Carbon Dioxide Technology is presented as nonthermal food processing.•Fundamentals and advantages and microbial inactivation mechanism are reported.•Previous studies covering the effects at the intrinsic quality parameters of dairy foods are also revised.
Pulmonary delivery of drugs has attracted increasing attention in healthcare, as the lungs are an easily accessible site for noninvasive systemic delivery of drugs. Although pulmonary inhalation of ...porous microparticles has been shown to sustain drug delivery, there are limited reports on efficient delivery of insulin and inhalation therapy of diabetes based on supercritical carbon dioxide (SC‐CO2) technology. Herein, this study reports the fabrication of insulin‐loaded poly‐l‐lactide porous microspheres (INS‐PLLA PMs) by using the SC‐CO2 technology, and their use as an inhalation delivery system potentially for diabetes therapy. Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are investigated. The PLLA PMs show negligible toxicity to lung‐derived cells, resulting in no significant reduction in cell viability, as well as levels of various inflammatory mediators such as interleukin (IL)‐6, IL‐8, and tumor necrosis factor‐α, compared with the negative control group. INS‐PLLA PMs are further efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats. Together, the results demonstrate that the INS‐PLLA PMs have a strong potential as an effective strategy for inhalation treatment of diabetes.
Highly efficient insulin‐loaded poly‐l‐lactide porous microspheres (INS‐PLLA PMs) are fabricated using the supercritical carbon dioxide technology for their use as an inhalation delivery system potentially for diabetes therapy. These biocompatible INS‐PLLA PMs can be efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in the induced diabetic rats.
The impact of nanotechnology and its advancements have allowed us to explore new therapeutic modalities. To this end, we designed nanoparticles-inlaid porous microparticles (NIPMs) coloaded with ...small interfering RNA (siRNA) and glucagon-like peptide-1 (GLP-1) using the supercritical carbon dioxide (SC–CO2) technology as an inhalation delivery system for diabetes therapy. siRNA-encapsulating chitosan (CS) nanoparticles were first synthesized by an ionic gelation method, which resulted in particles with small sizes (100–150 nm), high encapsulation efficiency (∼94.8%), and sustained release performance (∼60% in 32 h). These CS nanoparticles were then loaded with GLP-1-dispersed poly-l-lactide (PLLA) porous microparticles (PMs) by SC–CO2-assisted precipitation with the compressed antisolvent (PCA) process. The hypoglycemic efficacy of NIPMs administered via pulmonary route in mice persisted longer due to sustained release of siRNA from CS nanoparticles and the synergistic effects of GLP-1 in PMs, which significantly inhibited the expression of dipeptidyl peptidase-4 mRNA (DPP-4-mRNA). This ecofriendly technology provides a convenient way to fabricate nanoparticle-microparticle composites for codelivery of a gene and a therapeutic peptide, which will potentially find widespread applications in the field of pharmaceutics.
In article number 1800910 by Yu Shrike Zhang, Ai‐Zheng Chen, and co‐workers, insulin‐loaded poly‐l‐lactide porous microspheres (INS‐PLLA PMs) are fabricated by using supercritical fluid technology, ...serving as an inhalation delivery system potentially used towards diabetes therapy. The PLLA PMs show negligible toxicity to lung‐derived cells, and they are efficiently deposited in the trachea and the bronchi of the superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats.
Breviscapine (BRE) has significant efficacy in cardiovascular disease, but the poor water solubility of breviscapine affects its oral absorption and limits its clinical application. In this study, ...supercritical carbon dioxide (SCF-CO
) technology was used to improve the solubility and bioavailability of BRE loaded into mesoporous silica nanoparticles (MSNs).
The solubility of BRE in SCF-CO
was measured under various conditions to investigate the feasibility of preparing drug-loaded MSNs by using ultrasound-assisted solution-enhanced dispersion by supercritical fluids (USEDS). The preparation process of drug-loaded MSNs was optimized using the central composite design (CCD), and the optimized preparation was comprehensively characterized. Furthermore, the drug-loaded MSNs prepared by the conventional method were compared. Finally, the dissolution and bioavailability of the preparations were evaluated by in vitro release and pharmacokinetics study.
The solubility of BRE in SCF-CO
was extremely low which was suitable to prepare BRE-loaded MSNs by USEDS technology. The particle size of the preparation was 177.24 nm, the drug loading was 8.63%, and the specific surface area was 456.3m
/g. As compared to the conventional preparation method of solution impregnation-evaporation (SIV), the formulation prepared by USEDS technology has smaller particle size, higher drug loading, less residual solvent and better stability. The results of the in vitro release study showed that drug-loaded MSNs could significantly improve drug dissolution. The results of pharmacokinetics showed that the bioavailability of drug-loaded MSNs was increased 1.96 times compared to that of the BRE powder.
Drug-loaded MSNs can significantly improve the solubility and bioavailability of BRE, indicating a good application prospect for MSNs in improving the oral absorption of drugs. In addition, as a solid dispersion preparation technology, USEDS technology has incomparable advantages.
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