Para compra cialis puede ser visto como un desafío. Aumenta Smomenta, y todos los que se poco a poco abrumado, como es lógico, cada vez más hombres están diagnosticados con disfunción eréctil.

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Respiratory Drug Delivery 2008 – Xu et al.
Comparative Dispersion Study
of Dry Powder Aerosols of Albuterol
Sulfate/Lactose Monohydrate and
Disodium Cromoglycate/Lactose
Monohydrate Delivered by
Standardized Entrainment Tubes
Zhen Xu,1 Heidi M. Mansour,1 Tako Mulder,2 Richard McLean,3
John Langridge,2 and Anthony J. Hickey1
1School of Pharmacy, Division of Molecular Pharmaceutics, Dispersed Systems Laboratory , University of North Carolina, Chapel Hill, NC, USA 2DMV-Fonterra Excipients, Goch, Nordrhein-Westfalen, Germany KEYWORDS: dispersion, lactose monohydrate, standardized entrainment tubes,
emitted dose, fine particle fraction, mass median aerodynamic diameter,
dry powder formulation
INTRODUCTION
The dispersion studies using standardized entrainment tubes (SETs) represent inhaler device independent aerodynamic assessment of dry powder formulations (1). The well-defined airflow properties of SETs at given flow rate guarantee good reproducibility of drug deaggregation by overcoming the interparticulate forces, thus good correlation of airflow conditions of SETs with the aerodynamic powder properties including emitted dose (ED), fine particle fraction (FPF), and mass median aerodynamic diameter (MMAD), which are related to dispersion efficiency (2, 3).
Study Design: Particle sizing of drugs and carriers was performed using Malvern laser diffrac-tion for volume particle size determination. Drug/lactose monohydrate interactive physical blends were prepared at drug concentrations of 0.5% (w/w) and 2% (w/w). Experimentally designed aerosolization was performed via a series of four SETs with specific resistances (RD) encompass-ing those of commercial DPIs. The aerodynamic behavior of these blends was screened by directly connecting SETs at the mouth port with twin-stage liquid impinger (TSLI) or Anderson cascade 898
Comparative Dispersion Study of Dry Powder Aerosols of Albuterol Sulfate/Lactose . . . – Xu et al.
impactor (ACI) at the flow rate of 60 L/min. Both with and without solenoid switch actuation (10 sec) methods were evaluated. The ED, FPF, and MMAD of the dispersion data were correlated with airflow properties of SETs. A set of statistical comparison of these data by 2n full factorial design was performed to compare the dispersion efficiency of these blends. RESULTS AND DISCUSSION
Micronized drug particles were in the respirable size range (< 5 µm) with a narrow unimodal particle size distribution (Span < 0.5). Both sieved (SV) and milled (ML) lactose batches were in the comparable size range but markedly different particle size distribution. The overall trend of dispersion data (ED, FPF, MMAD) for each individual SET was independent of the presence of a solenoid switch (i.e. instantaneous vs delayed actuation). The ACI studies with ML lactose carriers and higher drug concentration gave higher FPF and lower MMAD than SV carriers. But only the data with solenoid switch gave consistently increased FPF and decreased MMAD across the increasing pressure drop, power, Reynold’s number and shear stress, which were in good cor-relation with the increasing degree of drug deaggregation (Table 1). The TSLI studies by means of full factorial statistical analysis indicated that the drug concentration was the least significant parameter on response among the other parameters including drugs, carriers, and SETs. For all studied formulations, disodium cromoglycate (DSCG)/lactose monohydrate blends gave superior dispersion efficiency (higher FPF and lower MMAD) to albuterol sulfate (AS)/lactose monohy-drate blends, indicating easier drug deaggregation of DSCG from lactose sugar carrier. This can be related to the significant interfacial activity of DSCG, and its ability to spontaneously reduce the surface energy of a polar surface (such as the surface of water or sugar). Similarly, the same trend of the dispersion efficiency of ML lactose carriers over the SV ones was observed. In view of the ED, SV lactose blends gave higher ED than ML blends, because of the better flow properties of the SV blends. The high shear SETs gave relatively lower ED than low shear ones, but the trend of ED difference among different formulations became less obvious in the high shear, presumably because of the increasing turbulence within the high shear SET. CONCLUSIONS
Both ACI and TSLI dispersion data obtained were in good agreement with each other. Although interparticulate adhesion forces were previously reported (4) to be stronger for pure sugar carri-er-free DSCG than AS, which can be attributed to spontaneous self-assembly behavior of pure DSCG and liquid crystalline formation, DSCG/lactose monohydrate blends had much superior aerosol performance leading to greater drug dispersion than AS/lactose monohydrate blends. For DSCG/sugar blends, the superior aerosol performance can be attributed to the strong interfacial energy-reducing properties of DSCG at polar interfaces, such as the surface of sugar and water. The increased surface fines of ML lactose blends could partly explain the increased FPF. Instan-taneous actuation with solenoid switch was necessary for consistent dispersion evaluation across different SET airflow conditions. In most cases, a trade-off between ED and FPF (or MMAD) was observed, but FPF and MMAD were more important factors in evaluating the dispersion efficiency. The results were indicative to make future prediction of the formulation for dry powder inhalers (DPIs), as well as examining the fundamental relationships between the interparticulate interactions and the dynamic aerosol performance when correlated with other characterization techniques.
Respiratory Drug Delivery 2008 – Xu et al.
hed) with A
s (with solenoid switc
T

G using SE
airflow parameters were shown previously (1) imental design and results of AS and DSC
er
xp
E

* Comparision includes: 2 tubes (lowest D (n = 2 with standard deviation in parentheses). SET 900
Comparative Dispersion Study of Dry Powder Aerosols of Albuterol Sulfate/Lactose . . . – Xu et al.
ACKNOWLEDGEMENTS
Generous financial support from the PhRMA Foundation, Pfizer, Inc., and DMV-Fonterra Excipients is gratefully acknowledged REFERENCES
1. Louey M.D. et al. (2006), “Standardized entrainment tubes for the evaluation of pharma- ceutical dry powder dispersion,” Journal of Aerosol Sci.; 37 (11): 1520-31.
2. Hickey, A.J., Mansour, H.M., et al. (2007), “Physical characterization of component particles included in dry powder inhalers. I. Strategy Review and Static Characteristics,” J Pharm Sci; 96(5): 1282-301.
3. Hickey, A.J., Mansour, H.M., et al. (2007), “Physical characterization of component particles included in dry powder inhalers. II. Dynamic characteristics,” J Pharm Sci; 96(5): 1302-19.
4. Young, P.M., Tobyn, M.J., et al. (2006), “The use of colloid probe microscopy to predict aerosolization performance in dry powder inhalers: AFM and in vitro correlation,” J. Pharm Sci; 95(8): 1800-9.

Source: http://pharmacy.mc.uky.edu/faculty/mansour/Mansour_RDD_08.pdf

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