Dry powder inhaler formulations : effect of carrier size on the drug dispersion

Background: The size of the carrier influences drug aerosolization from a dry powder inhaler (DPI) formulation. Lactose particles with irregular shape and rough surface in a variety of sizes are additionally used as carriers; however, contradictory reports exist regarding the effect of carrier size on the dispersion of drug. We examined the influence of the spherical particle size of the biodegradable polylactide-co-glycolide (PLGA) carrier on the aerosolization of a model drug, salbutamol sulphate (SS). Methods: Four different sizes (20-150 µm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were determined by laser diffraction and SEM, respectively. Results: The FPF was found to increase from 5.6% to 21.3% with increasing carrier sizeup to150 µm. Conclusions: The aerosolization of drug increased linearly with the size of polymer carriers. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Vibrational spectroscopy of the multianion mineral kemmlitzite (Sr,Ce)Al3(AsO4)(SO4)(OH)6

Some minerals are colloidal and show no X-ray diffraction patterns. Vibrational spectroscopy offers one of the few methods for the assessment of the structure of these types of mineral. Among this group of minerals is kemmlitzite (Sr,Ce)Al3(AsO4)(SO4)(OH)6. The objective of this research is to determine the molecular structure of the mineral kemmlitzite using vibrational spectroscopy. Raman microscopy offers a useful method for the analysis of such colloidal minerals. Raman and infrared bands are attributed to the AsO43- , SO42- and water stretching vibrations. The Raman spectrum is dominated by a very intense sharp band at 984 cm-1 assigned to the SO42- symmetric stretching mode. Raman bands at 690, 772 and 825 cm-1 may be assigned to the AsO43- antisymmetric and symmetric stretching modes. Raman bands observed at 432 and 465 cm-1 are attributable to the doubly degenerate 2 (SO4)2- bending mode. Vibrational spectroscopy is important in the assessment of the molecular structure of the kemmlitzite, especially when the mineral is non-diffracting or poorly diffracting.

Vibrational spectroscopic study of the mineral pitticite Fe, AsO4, SO4, H2O

Some minerals are colloidal and show no X-ray diffraction patterns. Vibrational spectroscopy offers one of the few methods for the determination of the structure of these minerals. Among this group of minerals is pitticite, simply described as (Fe, AsO4, SO4, H2O). In this work, the analogue of the mineral pitticite has been synthesised. The objective of this research is to determine the molecular structure of the mineral pitticite using vibrational spectroscopy. Raman and infrared bands are attributed to the AsO43−, SO42− and water stretching and bending vibrations. The Raman spectrum of the pitticite analogue shows intense peaks at 845 and 837 cm−1 assigned to the AsO43− stretching vibrations. Raman bands at 1096 and 1182 cm−1 are attributed to the SO42− antisymmetric stretching bands. Raman spectroscopy offers a useful method for the analysis of such colloidal minerals.

The mineral tooeleite Fe6(AsO3)4SO4(OH)4⋅4H2O – An infrared and Raman spectroscopic study-environmental implications for arsenic remediation

The mineral tooeleite Fe6(AsO3)4SO4(OH)4�4H2O is secondary ferric arsenite sulphate mineral which has environmental significance for arsenic remediation because of its high stability in the regolith. The mineral has been studied by X-ray diffraction (XRD), infrared (IR) and Raman spectroscopy. The XRD result indicates tooeleite can form more crystalline solids in an acid environment than in an alkaline environment. Infrared spectroscopy identifies moderately intense band at 773 cm�1 assigned to AsO3� 3 symmetric stretching vibration. Raman spectroscopy identifies three bands at 803, 758 and 661 cm�1 assigned to the symmetric and antisymmetric stretching vibrations of AsO3� 3 and As-OH stretching vibration respectively. In addition, the infrared bands observed at 1116, 1040, 1090, 981 and 616 cm�1, are assigned to the m3, m1 and m4 modes of SO2� 4 . The same bands are observed at 1287, 1085, 983 and 604 cm�1 in the Raman spectrum. As3d band at binding energy of 44.05 eV in XPS confirms arsenic valence of tooeleite is +3. These characteristic bands in the IR and Raman spectra provide useful basis for identifying the mineral tooeleite.

Neutralization of acid sulfate solutions using bauxite refinery residues and its derivatives

This investigation has shown that by transforming free caustic in red mud (RM) to Bayer hydrotalcite (during the seawater neutralization (SWN) process) enables a more controlled release mechanism for the neutralization of acid sulfate soils. The formation of hydrotalcite has been confirmed by X-ray diffraction (XRD) and differential thermalgravimetric analysis (DTG), while the dissolution of hydrotalcite and sodalite has been observed through XRD, DTG, pH plots, and ICP-OES. Coupling of all techniques enabled three neutralization mechanisms to be determined: (1) free alkali, (2) hydrotalcite dissolution, and (3) sodalite dissolution. The mechanisms are determined on the basis of ICP-OES and kinetic information. When the mass of RM or SWN-RM is greater than 0.08 g/50 mL, the pH of solution increases to a suitable value for plant life with aluminum leaching kept at a minimum. To obtain a neutralization pH greater than 6 in 10 min, the following ratio of bauxite residue (g) in 50 mL with a known iron sulfate (Fe2(SO4)3) concentration can be determined as follows: 0.04 g:50 mL:0.1 g/L of Fe2(SO4)3.

Carbonate cementation in sandstones of the Plover Formation, North West Shelf, W.A

Ancient sandstones include important reservoirs for hydrocarbons (oil and gas), but, in many cases, their ability to serve as reservoirs is heavily constrained by the effects of carbonate cements on porosity and permeability. This study investigated the controls on distribution and abundance of carbonate cements within the Jurassic Plover Formation, Browse Basin, North West Shelf, Australia. Samples were analysed petrographically with point counting of 59 thin sections and mineralogically with x-ray diffraction from two wells within the Torosa Gas Field. Selected samples were also analysed for stable isotopes of O and C. Sandstones are classified into eleven groups. Most abundant are quartzarenites and then calcareous quartzarenites. Lithology ranged between sandstones consisting of mostly quartz with scant or no carbonate in the form of cement or allochems, to sandstones with as much as 40% carbonate. The major sources of carbonate cement in Torosa 1 and Torosa 4 sandstones were found to be early, shallow marine diagenetic processes (including cementation), followed by calcite cementation and recrystallisation of cements and allochems during redistribution by meteoric waters. Blocky and sparry calcite cements, indicative of meteoric environments on the basis of stable isotope values and palaeotemperature assessment, overprinted the initial shallow marine cement phase in all cases and meteoric cements are dominant. Torosa 4 was influenced more by marine settings than Torosa 1, and thus has the greater potential for calcite cement. The relatively low compaction of calcite-cemented sandstones and the stable isotope data suggest deep burial cementation was not a major factor. Insufficient volcanic rock fragments or authigenic clay content infers alteration of feldspars was not a major source of calcite. Very little feldspar is present, altered or otherwise. Hence, increased alkalinity from feldspar dissolution is not a contributing factor in cement formation. Increased alkalinity from bacterial sulphate reduction in organic–rich fine sediments may have driven limited cementation in some samples. The main definable and significant source of diagenetic marine calcite cement originated from original marine cements and the nearby dissolution of biogenic sources (allochems) at relatively shallow depths. Later diagenetic fluids emplaced minor dolomite, but this cement did not greatly affect the reservoir quality in the samples studied.

Source apportionment of airborne particulate matter : an overview of Australian and New Zealand studies

Despite the existence of air quality guidelines in Australia and New Zealand, the concentrations of particulate matter have exceeded these guidelines on several occasions. To identify the sources of particulate matter, examine the contributions of the sources to the air quality at specific areas and estimate the most likely locations of the sources, a growing number of source apportionment studies have been conducted. This paper provides an overview of the locations of the studies, salient features of the results obtained and offers some perspectives for the improvement of future receptor modelling of air quality in these countries. The review revealed that because of its advantages over alternative models, Positive Matrix Factorisation (PMF) was the most commonly applied model in the studies. Although there were differences in the sources identified in the studies, some general trends were observed. While biomass burning was a common problem in both countries, the characteristics of this source varied from one location to another. In New Zealand, domestic heating was the highest contributor to particle levels on days when the guidelines were exceeded. On the other hand, forest back-burning was a concern in Brisbane while marine aerosol was a major source in most studies. Secondary sulphate, traffic emissions, industrial emissions and re-suspended soil were also identified as important sources. Some unique species, for example, volatile organic compounds and particle size distribution were incorporated into some of the studies with results that have significant ramifications for the improvement of air quality. Overall, the application of source apportionment models provided useful information that can assist the design of epidemiological studies and refine air pollution reduction strategies in Australia and New Zealand.

A review of the removal of anions and oxyanions of the halogen elements from aqueous solution by layered double hydroxides

The application of layered double hydroxides (LDHs) and thermally activated LDHs for the removal of various fluorine (F-, BF-4), chlorine (Cl-,ClO-4), bromine (Br-, BrO-3) and iodine (I-, IO-3) species from aqueous solutions has been reviewed in this article. LDHs and thermally activated LDHs were able to significantly reduce the concentration of selected anions in laboratory scale experiments. The M2+:M3+ cation ratio of the LDH adsorbent was an important factor which influenced anion uptake. Though LDHs were able to remove some target anion species through anion exchange and surface adsorption thermal activation and reformation generally produced better results. The presence of competing anions including carbonate, phosphate and sulphate had a significant impact on uptake of the target anion as LDHs typically exhibit lower affinity towards monovalent anions compared to anions with multiple charges. The removal of fluoride and perchlorate from aqueous solution by a continuous flow system utilising fixed bed columns packed with LDH adsorbents has also been investigated. The adsorption capacity of the columns at breakpoint was heavily dependent on the flow rate and lower than result reported for the corresponding batch methods. There is still considerable scope for future research on numerous topics summarised in this article.

Vibrational spectroscopy of the multianion mineral gartrellite from the Anticline Deposit, Ashburton Downs, Western Australia

The multianion mineral gartrellite PbCu(Fe3+,Cu)(AsO4)2(OH,H2O)2 has been studied by a combination of Raman and infrared spectroscopy. The molecular structure of gartrellite is assessed. Gartrellite is one of the tsumcorite mineral group based upon arsenate and/or sulphate anions. Crystal symmetry is either triclinic in the case of an ordered occupation of two cationic sites, triclinic due to ordering of the H bonds in the case of species with two water molecules per formula unit, or monoclinic in the other cases. Characteristic Raman spectra of the mineral gartrellite enable the assignment of the bands to specific vibrational modes. These spectra are related to the structure of gartrellite. The position of the hydroxyl and water stretching vibrations are related to the strength of the hydrogen bond formed between the OH unit and the AsO3/4 anion.

Dry powder inhaler formulations-effect of polymer carrier size on the drug dispersion

Background The size of the carrier influences the aerosolization of drug from a dry powder inhaler (DPI) formulation. Currently, lactose monohydrate particles in a variety of sizes are preferably used in carrier based DPI formulations of various drugs; however, contradictory reports exist regarding the effect of the size of the carrier on the dispersion of drug. In this study we examined the influence of the intrinsic particle size of the polymeric carrier on the aerosolization of a model drug salbutamol sulphate (SS). Methods Four different sizes (20–150 lm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS particles from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were by laser diffraction and SEM, respectively. Results The FPF from these carriers was found to be increasing from 5.6% to 21.3% with increasing the carrier size. The FPF was found to be greater (21%) with the highest particle size of the carrier (150 lm). Conclusions The aerosolization of drug was dependent on the size of polymer carriers. The smaller size of the carrier resulted in lower FPF which was increased with increasing the carrier size. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Colloidal drug probe : method development and validation for adhesion force measurement using atomic force microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between the drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from a dry powder inhaler (DPI) formulation. Initially model silica probes of approximately 4 μm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres preattached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Molecular structural studies of the amorphous mineral pitticite Fe, AsO4, SO4, H2O

Some minerals are colloidal and show no X-ray diffraction patterns. Vibrational spectroscopy offers one of the few methods for the assessment of the structure of these types of mineral. Among this group of minerals is pitticite simply described as Fe, AsO4, SO4, H2O. The objective of this research is to determine the molecular structure of the mineral pitticite using vibrational spectroscopy. Raman microscopy offers a useful method for the analysis of such colloidal minerals. Raman and infrared bands are attributed to the , and water stretching vibrations. The Raman spectrum is dominated by a very intense sharp band at 983 cm−1 assigned to the symmetric stretching mode. A strong Raman band at 1041 cm−1 is observed and is assigned to the antisymmetric stretching mode. Low intensity Raman bands at 757 and 808 cm−1 may be assigned to the antisymmetric and symmetric stretching modes. Raman bands observed at 432 and 465 cm−1 are attributable to the doubly degenerate ν2(SO4)2- bending mode.

Vibrational spectroscopic characterization of the sulphate–halide mineral sulphohalite – implications for evaporites

The mineral sulphohalite – Na6(SO4)2FCl is a rare sodium halogen sulphate and occurs associated with evaporitic deposits. Sulphohalite formation is important in saline evaporites and in pipe scales. Sulphohalite is an anhydrous sulphate–halide with an apparent variable anion ratio of formula Na6(SO4)2FCl. Such a formula with oxyanions lends itself to vibrational spectroscopy. The Raman band at 1003 cm−1 is assigned to the (SO4)2− ν1 symmetric stretching mode. Shoulders to this band are found at 997 and 1010 cm−1. The low intensity Raman bands at 1128, 1120 and even 1132 cm−1 are attributed to the (SO4)2− ν3 antisymmetric stretching vibrations. Two symmetric sulphate stretching modes are observed indicating at least at the molecular level the non-equivalence of the sulphate ions in the sulphohalite structure. The Raman bands at 635 and 624 cm−1 are assigned to the ν4 SO42− bending modes. The ν2 (SO4)2− bending modes are observed at 460 and 494 cm−1. The observation of multiple bands supports the concept of a reduction in symmetry of the sulphate anion from Td to C3v or even C2v. No evidence of bands attributable to the halide ions was found.

Observations on the formation, growth and chemical composition of aerosols in an urban environment

The charge and chemical composition of ambient particles in an urban environment were determined using a Neutral Particle and Air Ion Spectrometer and an Aerodyne compact Time-Of-Flight Aerosol Mass Spectrometer. Particle formation and growth events were observed on 20 of the 36 days of sampling, with eight of these events classified as strong. During these events, peaks in the concentration of intermediate and large ions were followed by peaks in the concentration of ammonium and sulphate, which were not observed in the organic fraction. Comparison of days with and without particle formation events revealed that ammonium and sulphate were the dominant species on particle formation days while high concentrations of biomass burning OA inhibited particle growth. Analyses of the degree of particle neutralisation lead us to conclude that an excess of ammonium enabled particle formation and growth. In addition, the large ion concentration increased sharply during particle growth, suggesting that during nucleation the neutral gaseous species ammonia and sulphuric acid react to form ammonium and sulphate ions. Overall, we conclude that the mechanism of particle formation and growth involved ammonia and sulphuric acid, with limited input from organics.

Chemical and bioanalytical assessment of coal seam gas associated water

A comprehensive study was undertaken involving chemical (inorganic and organic) and bioanalytical (a suite of 14 in vitro bioassays) assessments of coal seam gas (coal bed methane) associated water (CSGW) in Queensland, Australia. CSGW is a by-product of the gas extraction process and is generally considered as water of poor quality. This was done to better understand what is known about the potential biological and environmental effects associated with the organic constituents of CSGW in Australia. In Queensland, large amounts of associated water must be withdrawn from coal seams to allow extraction of the gas. CSGW is disposed of via release to surface water, reinjected to groundwater or reused for irrigation of crops or pasture, supplied for power station cooling and or reinjected specifically to augment drinking water aquifers. Groundwater samples were collected from private wells tapping into the Walloon Coal Measures, the same coal aquifer exploited for coal seam gas production in the Surat Basin, Australia. The inorganic characteristics of these water samples were almost identical to the CSGW entering the nearby gas company operated Talinga-Condabri Water Treatment Facility. The water is brackish with a pH of 8 to 9, high sodium, bicarbonate and chloride concentrations but low calcium, magnesium and negligible sulphate concentrations. Only low levels of polyaromatic hydrocarbons (PAHs) were detected in the water samples, and neither phenols nor volatile organic compounds were found. Results from the bioassays showed no genotoxicity, protein damage, or activation of hormone receptors (with the exception of the estrogen receptor). However, five of the 14 bioassays gave positive responses: an arylhydrocarbon-receptor gene activation assay (AhR-CAFLUX), estrogenic endocrine activity (ERα-CALUX), oxidative stress response (AREc32), interference with cytokine production (THP1-CPA) and non-specific toxicity (Microtox). The observed effects were benchmarked against known water sources and were similar to secondary treated wastewater effluent, stormwater and surface water. As mixture toxicity modelling demonstrated, the detected PAHs explained less than 5% of the observed biological effects.