Formation of nanocarrier systems by dense gas processing.

Nanocarrier systems, such as liposomes, polymersomes, and micelles, find applications in the delivery of a wide range of compounds, including targeted delivery of pharmaceuticals. Nanocarrier systems have the ability to increase the bioavailability, reduce toxicity, and avoid undesirable interactions of active pharmaceutical ingredients. In this work, a novel dense gas technique known as depressurization of an expanded solution into aqueous media (DESAM) was used to produce different types of nanocarrier systems. The effects of using different types of dense gases and different operating temperatures were investigated. Encapsulation of hydrophilic compounds in the vesicles (liposomes and polymersomes) was also studied. The highest encapsulation efficiencies in liposomes and polymersomes achieved were 10.2 and 9.7%, respectively. The DESAM process was also able to reduce the residual solvent content in the product to 2.2% (v/v), which is significantly lower than the solvent residual levels reported for conventional processing.

Application of a dense gas technique for sterilizing soft biomaterials.

Sterilization of soft biomaterials such as hydrogels is challenging because existing methods such as gamma irradiation, steam sterilization, or ethylene oxide sterilization, while effective at achieving high sterility assurance levels (SAL), may compromise their physicochemical properties and biocompatibility. New methods that effectively sterilize soft biomaterials without compromising their properties are therefore required. In this report, a dense-carbon dioxide (CO(2) )-based technique was used to sterilize soft polyethylene glycol (PEG)-based hydrogels while retaining their structure and physicochemical properties. Conventional sterilization methods such as gamma irradiation and steam sterilization severely compromised the structure of the hydrogels. PEG hydrogels with high water content and low elastic shear modulus (a measure of stiffness) were deliberately inoculated with bacteria and spores and then subjected to dense CO(2) . The dense CO(2) -based methods effectively sterilized the hydrogels achieving a SAL of 10(-7) without compromising the viscoelastic properties, pH, water-content, and structure of the gels. Furthermore, dense CO(2) -treated gels were biocompatible and non-toxic when implanted subcutaneously in ferrets. The application of novel dense CO(2) -based methods to sterilize soft biomaterials has implications in developing safe sterilization methods for soft biomedical implants such as dermal fillers and viscosupplements.

Dense gas processing of polymeric controlled release formulations.

Dense gas techniques, which utilize the properties of fluids in the vicinity of their critical points, are of increasing interest in the processing of pharmaceuticals. It is generally known that dense gases can be used for extractions, chromatographic separations and chemical synthesis due to their liquid-like solvation power and gas-like mass-transfer properties. The processes can be conducted at moderate operating conditions and are thus suitable for many heat-labile compounds such as proteins, biocompatible polymers and pharmaceuticals. Recent applications of dense gas techniques include micronization, crystallization of high-purity particles, sterilization and preparation of microencapsulated drug formulations. The following paper provides a brief overview of dense gases and various processing techniques to fabricate polymeric drug-loaded formulations for controlled release purposes.

Improving the dissolution properties of curcumin using dense gas antisolvent technology.

The dissolution properties of curcumin are notoriously poor and hinder its bioavailability. To improve its dissolution properties, curcumin has been formulated with methyl-ß-cyclodextrin and polyvinylpyrrolidone by the atomized rapid injection solvent extraction (ARISE) system. The compounds were co-precipitated from organic solutions using carbon dioxide at 30°C and 95bar as the antisolvent. Curcumin formulations were also produced by physical mixing and freeze drying for comparative purposes. The morphology, crystallinity, solid state molecular interactions, apparent solubility and dissolution profiles of samples were observed. The results indicate that the ARISE process is effective in the preparation of curcumin micro-composites with enhanced dissolution profiles compared to unprocessed material and products from physical mixing and freeze drying.

A critical review of the arsenic uptake mechanisms and phytoremediation potential of Pteris vittata.

The discovery of the arsenic hyperaccumulator, Pteris vittata (Chinese brake fern), has contributed to the promotion of its application as a means of phytoremediation for arsenic removal from contaminated soils and water. Understanding the mechanisms involved in arsenic tolerance and accumulation of this plant provides valuable tools to improve the phytoremediation efficiency. In this review, the current knowledge about the physiological and molecular mechanisms of arsenic tolerance and accumulation in P. vittata is summarized, and an attempt has been made to clarify some of the unresolved questions related to these mechanisms. In addition, the capacity of P. vittata for remediation of arsenic-contaminated soils is evaluated under field conditions for the first time, and possible solutions to improve the remediation capacity of Pteris vittata are also discussed.

Particle formation of budesonide from alcohol-modified subcritical water solutions.

Recently, subcritical water (SBCW: water that has been heated to a temperature between 100°C and 200°C at pressures of up to 70bar) has been used to dissolve several hydrophobic pharmaceutical compounds (Carr et al., 2010a). Furthermore, a number of active pharmaceutical ingredients (APIs) have been rapidly precipitated from SBCW solutions (Carr et al., 2010b,c). It is possible to alter the precipitate morphology by altering the processing variables; including the SBCW-API solution injection temperature and adding impurities (such as pharmaceutical excipients, e.g. lactose) to the precipitation chamber. The work presented in this article demonstrates that the morphology of pharmaceutical particles can be tuned by adding organic solvents (ethanol and methanol) to the SBCW-API solutions. Particle morphology has also been tuned by adding different pharmaceutical excipients (polyethylene glycol 400 and lactose) to the precipitation chamber. Different morphologies of pharmaceutical particles were produced, ranging from nanospheres of 60nm diameter to 5µm plate particles. Budesonide was used as the model API in this study. Two experimental products were spray dried to form dry powder products. The aerodynamic particle size of the powder was established by running the powder through an Andersen Cascade Impactor. It has been shown that the drug particles produced from the SBCW micronization process, when coupled with a spray drying process, are suitable for delivery to the lungs.

Effect of calcium on growth performance and essential oil of vetiver grass (Chrysopogon zizanioides) grown on lead contaminated soils.

The aim of this study was to investigate effect of calcium on growth, survival, essential oil yield and chemical compositions of vetiver grass grown on lead contaminated soils. Calcium inform of CaCO3 (0, 2000, 4000, 6000 mg Ca kg(-1)) was added to river sand soils containing 4000 mg Pb kg(-1) dry soil. Results showed that, in the absence of calcium treatment, no plants survived after 2 weeks of cultivation, while the rest grew well to the end of the experimental period (42 weeks). Calcium treatments generally resulted in a slight decrease in biomass. Interestingly, an increase in calcium over 2000 mg kg(-1) did not result in a decrease in accumulation of lead in vetiver roots and shoots. The levels of lead in roots and shoots under calcium treatments were around 2000 and 90 mg kg(-1) dry weight, respectively. The addition of CaCO3 did not improve vetiver essential oil yield and chemical composition compared to the control. A level of applied CaCO3 about half of the lead concentration in soils was sufficient to improve vetiver growth and survival, and accumulate high concentrations of lead in the roots. This finding can be applied for re-vegetation of lead contaminated soils using vetiver.

Economic incentive for applying vetiver grass to remediate lead, copper and zinc contaminated soils.

The application of vetiver grass (Chrysopogon zizaniodes) for phytoremediation of heavy metal contaminated soils can be promoted by economic return through essential oil production. Four levels of lead (0, 500, 2000, and 8000 mg kg(-1) dry soil), copper (0, 100, 400, and 1600 mg kg(-1) dry soil) and zinc (0, 400, 1600, and 6400 mg kg(-1) dry soil) were used to study their effects on vetiver growth, essential oil composition and yield. This study also investigated the effect of nitrogen concentrations on vetiver oil yield. Vetiver accumulated high concentrations of Pb, Cu and Zn in roots (3246, 754 and 2666 mg kg(-1), respectively) and small amounts of contaminants in shoots (327, 55, and 642 mg kg(-1), respectively). Oil content and yield were not affected at low and moderate concentrations of Cu and Zn. Only the application of Pb had a significant detrimental effect on oil composition. Extraction of vetiver essential oils by hydrodistillation produced heavy metal free products. High level of nitrogen reduced oil yields. Results show that phytoremediation of Cu and Zn contaminated soils by vetiver can generate revenue from the commercialization of oil extracts.

Vetiver grass, Vetiveria zizanioides: a choice plant for phytoremediation of heavy metals and organic wastes.

Glasshouse and field studies showed that Vetiver grass can produce high biomass (>100t/ tha(-1) year(-1)) and highly tolerate extreme climatic variation such as prolonged drought, flood, submergence and temperatures (-15 degrees - 55 degrees C), soils high in acidity and alkalinity (pH 3.3-9.5), high levels of Al (85% saturation percentage), Mn (578 mg kg(-1)), soil salinity (ECse 47.5 dS m(-1)), sodicity (ESP 48%), anda wide range of heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, Se, and Zn). Vetiver can accumulate heavy metals, particularly lead (shoot 0.4% and root 1%) and zinc (shoot and root 1%). The majority of heavy metals are accumulated in roots thus suitable for phytostabilization, and for phytoextraction with addition of chelating agents. Vetiver can also absorb and promote biodegradation of organic wastes (2,4,6-trinitroluene, phenol, ethidium bromide, benzo[a]pyrene, atrazine). Although Vetiver is not as effective as some other species in heavy metal accumulation, very few plants in the literature have a wide range of tolerance to extremely adverse conditions of climate and growing medium (soil, sand, and railings) combined into one plant as vetiver. All these special characteristics make vetiver a choice plant for phytoremediation of heavy metals and organic wastes.

Dense gas processing of micron-sized drug formulations incorporating hydroxypropylated and methylated beta-cyclodextrin.

PURPOSE: Because of their importance in pharmaceutical applications, hydroxypropyl-beta-cyclodextrin and methyl-beta-cyclodextrin have been selected to study the formation of micronized complexes incorporating active pharmaceutical ingredients (APIs) and cyclodextrins (CDs) by dense gas (DG) processing. METHODS: A single-step DG technique was used as an alternative to conventional methods for the manufacturing of API/CD complexes. The DG technology is highly attractive in the pharmaceutical industry because of its potential to generate micronized particles with controlled particle size distributions at moderate operating conditions. The effect of the aerosol solvent extraction system (ASES) processing on the dissolution performance of naproxen (NPX) was examined. RESULTS: The CDs were produced as microspheres smaller than 3 microm. The coprecipitation of each CD with NPX resulted in the production of microparticles with enhanced dissolution rates. CONCLUSIONS: The ASES was operated under mild conditions and generated micron-sized spherical particles that could be of particular interest in formulations for pulmonary delivery. Particular advantages of the technique are that (1) nontoxic solvents are used, and (2) it is suitable for the processing of thermally labile compounds. The proposed process can create opportunities to improve current administration routes and exploit novel delivery systems for drug formulations incorporating CDs.