Improved aerosolization performance of salbutamol sulfate formulated with lactose crystallized from binary mixtures of ethanol-acetone

It has been shown that dry powder inhaler (DPI) formulations typically achieve low fine particle fractions (poor performance). A commonly held theory is that this is due, at least in part, to low levels of detachment of drug from lactose during aerosolization as a result of strong adhesion of drug particles to the carrier surfaces. Therefore, the purpose of the present study is to overcome poor aerosolization performance of DPI formulation by modification of lactose particles. Lactose particles were crystallized by adding solution in water to different ratios of binary mixtures of ethanol-acetone. The results showed that modified lactose particles had exceptional aerosolization performance that makes them superior to commercial lactose particles. Morphology assessment showed that crystallized lactose particles were less elongated, more irregular in shape, and composed of smaller primary lactose particles compared with commercial lactose. Solid-state characterization showed that commercial lactose particles were α-lactose monohydrate, whereas crystallized lactose particles were a mixture of α-lactose monohydrate and β-lactose according to the ratio of ethanol-acetone used during crystallization process. The enhanced performance could be mainly due to rougher surface and/or higher amounts of fines compared with the lactose crystallized from pure ethanol or commercial lactose. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

Factors Affecting Serum Concentrations of Hepatitis C Virus (HCV) RNA in HCV Genotype 1-Infected Patients with Chronic Hepatitis▿

The serum concentration of hepatitis C virus (HCV) RNA is usually stable (4 to 8 log10 IU/ml) in untreated patients with chronic hepatitis C. While this baseline HCV RNA concentration ([HCV RNA]BL) is predictive of a sustained virologic response to treatment, its determinants are only partially identified. We therefore analyzed the baseline characteristics of 2,472 HCV genotype 1-infected patients to identify correlations with gender, age, race, weight, body mass index (BMI), HCV acquisition mode, HCV subtype, alanine aminotransferase concentration, or histopathologic changes in the liver. After separation of the data according to four [HCV RNA]BL groups (≤5.0, >5.0 to 5.6, >5.6 to 5.9, and >5.9 log10 IU/ml), we determined that increasing [HCV RNA]BL correlated (P < 0.05) with increasing proportions of patients who were male, >40 years of age, or heavier (a weight of >85 kg or a BMI of >27 kg/m2). Histologic activity index (HAI) data were available for 1,304 of these patients: increasing [HCV RNA]BL correlated with higher fibrosis and necrosis-inflammation scores. As a continuous variable, [HCV RNA]BL correlated with age, gender, weight (continuous or ≤85 versus >85 kg), BMI (continuous or ≤27 versus >27 kg/m2), subtype, fibrosis score, and necrosis-inflammation score; however, multiple-regression analysis yielded P values of <0.1 only for age, gender, BMI (≤27 versus >27 kg/m2), and fibrosis score. While our findings are suggestive of a role for these factors in maintenance of the pretreatment state of HCV infection, the multiple-regression model accounted for only ≤4.6% of the [HCV RNA]BL differences between individuals (R2 = 0.046 for 1,304 patients with HAI scores; 0.043 for all 2,472 patients)

Engineered mannitol as an alternative carrier to enhance deep lung penetration of salbutamol sulphate from dry powder inhaler

In this research mannitol particles were prepared by recrystallisation using non-solvent precipitation technique to investigate the effect of engineered carrier particles on their physicochemical properties and the in vitro deposition profiles of a model drug (salbutamol sulphate (SS)) from a dry powder inhaler (DPI). To this end, mannitol aqueous solution (15%, w/v) was added to different ratios of ethanol:water (100:0, 95:5, 90:10 and 85:15) to obtain mannitol particles. These crystallised mannitol particles were analysed in terms of micromeritic properties, morphology, DSC, FT-IR, and in vitro fine particle fraction (FPF) and emitted dose (ED) of SS. The results showed that the elongation ratio of all the recrystallised mannitol batches was higher than the original material giving them a needle-shaped morphology. Salbutamol sulphate deposition profiles from DPI formulation containing recrystallised needle-shaped mannitol showed enhanced performance and better delivery to the lower MSLI stages. The FPF increased from 15.4 ± 1.1 to 45.8 ± 0.7% when the commercial mannitol was replaced by mannitol crystallised from ethanol:water (90:10). This improvement could be due to the presence of elongated mannitol crystals in formulation blends. Solid state characterisation of engineered mannitol showed that the commercial mannitol was β-form, mannitol recrystallised from ethanol:water (85:15) was α-form and that samples recrystallised in presence of pure ethanol or other ratios of ethanol:water (95:5 and 90:10) were the mixtures of α-, β- and δ-forms. Multi-solvent recrystallisation technique was proved to have potential to produce mannitol crystals suitable for enhanced aerosolisation efficiency. Comparing different crystallised mannitol formulations showed that the final form (the type of polymorph) of the crystallised mannitol does not have a substantial effect on salbutamol sulphate aerosolisation performanc

Integrated assessment of water resources: Australian experiences

It is widely accepted that water resource management demands an integrated assessment of resource use options, including local and regional impacts on the environment and stakeholders. Multiple issues, stakeholders and scales of system behaviour must be considered, as well as the key disciplines within and between the human and natural sciences. Modelling is a critical tool in integrated assessment. It enables effects of policy interventions, climate forcing and demographics to be predicted (although with some uncertainty), and provides a means of expanding understanding of river basin behaviour. It also acts as a vehicle for social learning among various interest groups. This paper discusses the various frameworks and methods being used for integrated modelling, and their suitability and unfulfilled potential for these purposes. The frameworks include coupled component models, systems dynamics models, metamodels, risk-assessment approaches, Bayesian decision networks, agent-based methods, expert systems and other heuristic knowledge-based techniques. Specific software platforms are not considered but the lessons from software development and implementation are clearly spelt out. The paper presents three Australian case studies in integrated assessment. They vary in their range of catchment/watershed sizes, hydroclimatology, issues of concern and stakeholders engaged. Two of them utilise a coupled component modelling framework and the third a Bayesian decision network approach. The paper illustrates the value, problems and lessons of integrated assessment and modelling. In particular it proposes some ways to address the challenges of assessing options to obtain more sustainable basin-wide outcomes

Using remote sensing data for monitoring rock glacier distribution in the Bolivian Andes : implications for water supply

Annex 24 of final reportIt is now evident that warming in the tropical Andes due to climate change has a measurable impact on ice glaciers, which are known to have receded over the past decades, affecting water supply. Many large cities in the South American Andes are located above 2500m and rely almost entirely on high-altitude water stocks. This research focuses on rock glaciers in the Bolivian Andes. Remote sensing data sources including historic air photos, fine spatial resolution satellite data (IKONOS 5 m resolution), global-extent Digital Elevation Models, and Google Earth, are used to establish a detailed spatial understanding of rock glacier physical characteristics