Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids

Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer® (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), α1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions

Chalcophile and platinum-group element distribution in pyrites from the sulfide-rich pods of the Lac des Iles Pd deposits, Western Ontario, Canada : implications for post-cumulus re-equilibration of the ore and the use of pyrite compositions in exploration

The Lac des Iles Pd-deposits are atypical within the scope of platinum-group element (PGE) deposits. This is because the deposits do not resemble a classical PGE deposit in a number of ways: the intrusion is small and concentrically zoned; most of the host rocks to the deposits no longer have a primary mineralogy and equilibrated under greenschist conditions; the textures of the rocks from the ore zones are extremely variable; and the ores have very high Pd/Ir and Pd/Pt ratios. In addition to the disseminated sulfides, there are sulfide-rich pods present throughout the stratigraphy. The sulfide mineral textures and proportions within the pods vary from those which are essentially magmatic to those which consist predominantly of pyrite. The pyrite could have been deposited from hydrothermal fluids or it could have formed by alteration of magmatic sulfides. In order to distinguish between these two origins, the PGE and chalcophile element contents of the pyrite were investigated. It was found that the pyrite contains Os, Ir, Ru and Rh. These elements also concentrate in the magmatic sulfides pyrrhotite and pentlandite. Their presence in the pyrite could be explained by redistribution of Fe from pyrrhotite to silicate minerals that are present within and around the sulfide pods, possibly during cooling. Maps of the distribution of the elements show that there is zoning of the elements. The IPGE–Rh are present towards the cores of pyrite along with As whereas Co and Se are present towards the rims. Mobile elements such as Pb, Bi and Ag are present in thin overgrowths at the edges of pyrite and in a few cases, Pt, Te and Sn are also present in the overgrowths. Comparison of the composition and element distribution with pyrites from other igneous settings (Sudbury and Aguablanca) shows similarities, suggesting a common ore-modifying process. In contrast, pyrites from low-temperature hydrothermal deposits have different compositions. A plot of Co/Se vs Sb/As appears to be effective at separating the igneous pyrites from pyrites found in other settings and could possibly be used in exploration

Trace element distribution in primary sulfides and Fe–Ti oxides from the sulfide-rich pods of the Lac des Iles Pd deposits, Western Ontario, Canada : Constraints on processes controlling the composition of the ore and the use of pentlandite compositions in exploration

There is an on-going debate as to whether the Lac des Iles Pd deposits (Ontario, Canada) are of magmatic or hydrothermal origin. An aspect of the deposits that has not yet been documented is the presence of sulfide-rich pods which occur throughout the host intrusion (the Mine Block Intrusion). The ore mineralogy of the sulfide-rich pods consists of pyrrhotite, pentlandite, chalcopyrite, ± pyrite, magnetite and ilmenite. We present the trace element concentrations of pyrrhotite, pentlandite, chalcopyrite, magnetite, and ilmenite from the pods and compare these results with results from other Ni–Cu–platinum-group element (PGE) deposits. The low concentrations of Si and Ca and high concentrations of V, Ni, and Cr in magnetite are consistent with a magmatic origin of the magnetite. Variations in the V and Cr concentrations indicate that magnetite crystallized from a magmatic sulfide liquid during crystal fractionation of the sulfide liquid. The enrichments in Ni, Co, Os, Ir, Ru, and Rh and depletions in Cu, Ag, Cd, and Zn in pentlandite and pyrrhotite relative to chalcopyrite are also consistent with the formation of the pods by crystallization of a magmatic sulfide liquid. Comparison of pyrrhotite and pentlandite compositions from Lac des Iles with those from other Ni–Cu–PGE deposits shows that pyrrhotite and pentlandite derived from evolved magmas have distinct compositions relative to those derived from more primitive magmas. In addition, this comparison shows that pentlandites from PGE-dominated deposits are richer in Pd and Rh than pentlandites from Ni–Cu sulfide deposits. A plot of Pd vs Rh appears to be effective at distinguishing pentlandites of PGE-dominated deposits from those of Ni–Cu sulfide deposits and could possibly be used to adapt exploration strategies

Petrogenesis of massive sulphides from the Lac-des-Iles Palladium ore deposits, Western Ontario, Canada

Previously characterised as a sulphide-poor Pd ore deposit, massive sulphides have recently been discovered in Lac-des-Iles. The massive sulphides occur across the different lithological units and show variable degrees of alteration. The least altered samples comprise a typical magmatic assemblage of pyrrhotite, pentlandite and chalcopyrite. Chalcopyrite-rich samples are found at the edges of the pyrrhotite/pentlandite-rich pods. Base metal and platinum-group element (PGE) compositions indicate that as a whole they represent a frozen sulphide liquid, different from the one that formed the sulphide-poor samples, that was injected along structural features. The altered samples are rich in pyrite and magnetite. Molecular proportions of base metals and S/Se ratios are the same for the altered and unaltered samples indicating that neither S nor Fe has been remobilized from the system. We propose instead that oxidation was responsible for the observed changes in mineralogy. This alteration event appears not to have affected the PGE content

Sulfide-rich pods from the Lac-des-Îles Pd-ORE deposits, Western Ontario, Canada : Part 2. The origin of platinum-group elementsbearing pyrites

Pyrite from Lac-des-lies sulfide-rich pods host substantial amounts of platinum-group elements (PGE). In this contribution we discuss the origin of pyrite and their PGE content

Geology, petrography, geochemistry, and genesis of sulfide-rich pods in the Lac des Iles palladium deposits, western Ontario, Canada

The Lac des Iles Pd deposits are known for their Pd-rich sulfide-poor mineralization. However, previously undocumented sulfide-rich pods also occur within the intrusion that hosts the deposits. Given the complex magmatic and hydrothermal history of the mineralization at Lac des Iles, the sulfide-rich pods could have crystallized from magmatic sulfide liquids or precipitated from hydrothermal fluids. Sulfide-rich pods occur throughout the stratigraphy, in all rock types, and along comagmatic shear zones, and contain net-textured to massive sulfides. They can be divided into four main groups based on the variation in mineral assemblages: (1) pyrrhotite–pentlandite ± pyrite–chalcopyrite–magnetite–ilmenite; (2) chalcopyrite ± pyrrhotite–pentlandite–pyrite–magnetite–ilmenite; (3) pyrite ± pentlandite–chalcopyrite–pyrrhotite–magnetite–ilmenite; and (4) magnetite ± ilmenite–pyrrhotite–pentlandite–pyrite–chalcopyrite. Whole rock metal contents and S isotopic compositions do not change with the amount of pyrite present, except for slight enrichments in As and Bi. The presence of an essentially magmatic sulfide mineral assemblage (pyrrhotite–pentlandite ± chalcopyrite) with pentlandite exsolution flames in pyrrhotite in some pods suggests that the pods crystallized from magmatic sulfide liquids. The very low Cu contents of the pods suggests that they are mainly cumulates of monosulfide solid solution (MSS). We propose a model whereby sulfide liquids were concentrated into dilation zones prior to crystallizing cumulus MSS. Intermediate solid solution crystallized from the fractionated liquids at the edges of some pods leaving residual liquids enriched in Pt, Pd, Au, As, Bi, Sb, and Te. These residual liquids are no longer associated with the pods. During subsequent alteration, pyrite replaced MSS/pyrrhotite, but this did not affect the platinum-group element contents of the pods

Sulfide-rich pods from the Lac-des-Îles Pd-ORE deposits, Western Ontario, Canada : Part 1. A genetic model

Massive sulfide pods from the Lac-des-lies Pd-ore deposits (Western Ontario, Canada) show a variation in sulfide mineralogy and texture from essentially magmatic (pyrrhotite+pentlandite±chalcopyrite) to highly altered (pyrite±pentlandite±pyrrhotite±chalcopyrite). We suggest that the magmatic assemblage formed from crystallization of magmatic sulfide liquid. The pyrite (Py)-rich assemblage formed by Fe-loss to the surrounding silicates

Trace element distribution in primary sulfides and Fe–Ti oxides from the sulfide-rich pods of the Lac des Iles Pd deposits, Western Ontario, Canada : Constraints on processes controlling the composition of the ore and the use of pentlandite compositions in exploration

There is an on-going debate as to whether the Lac des Iles Pd deposits (Ontario, Canada) are of magmatic or hydrothermal origin. An aspect of the deposits that has not yet been documented is the presence of sulfide-rich pods which occur throughout the host intrusion (the Mine Block Intrusion). The ore mineralogy of the sulfide-rich pods consists of pyrrhotite, pentlandite, chalcopyrite, ± pyrite, magnetite and ilmenite. We present the trace element concentrations of pyrrhotite, pentlandite, chalcopyrite, magnetite, and ilmenite from the pods and compare these results with results from other Ni–Cu–platinum-group element (PGE) deposits. The low concentrations of Si and Ca and high concentrations of V, Ni, and Cr in magnetite are consistent with a magmatic origin of the magnetite. Variations in the V and Cr concentrations indicate that magnetite crystallized from a magmatic sulfide liquid during crystal fractionation of the sulfide liquid. The enrichments in Ni, Co, Os, Ir, Ru, and Rh and depletions in Cu, Ag, Cd, and Zn in pentlandite and pyrrhotite relative to chalcopyrite are also consistent with the formation of the pods by crystallization of a magmatic sulfide liquid. Comparison of pyrrhotite and pentlandite compositions from Lac des Iles with those from other Ni–Cu–PGE deposits shows that pyrrhotite and pentlandite derived from evolved magmas have distinct compositions relative to those derived from more primitive magmas. In addition, this comparison shows that pentlandites from PGE-dominated deposits are richer in Pd and Rh than pentlandites from Ni–Cu sulfide deposits. A plot of Pd vs Rh appears to be effective at distinguishing pentlandites of PGE-dominated deposits from those of Ni–Cu sulfide deposits and could possibly be used to adapt exploration strategies