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https://www.readbyqxmd.com/read/28645838/sensitivity-analysis-and-uncertainty-quantification-in-pulmonary-drug-delivery-of-orally-inhaled-pharmaceuticals
#1
Jun Lu, Jinxiang Xi, Joseph E Langenderfer
In spite of widespread use of modeling tools in inhalation dosimetry, it remains difficult to quantify the output uncertainties when subjected to various sources of input variability. This study aimed to develop a computational model that can quantify the input sensitivity and output uncertainty in pulmonary drug delivery by coupling probabilistic analysis package NESSUS with ANSYS Fluent. An image-based mouth-lung model was used to simulate the transport and deposition of drug particles and variability in particle size, density, and inhalation speed were considered...
June 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28643237/small-airway-absorption-and-microdosimetry-of-inhaled-corticosteroid-particles-after-deposition
#2
P Worth Longest, Michael Hindle
PURPOSE: To predict the cellular-level epithelial absorbed dose from deposited inhaled corticosteroid (ICS) particles in a model of an expanding and contracting small airway segment for different particle forms. METHODS: A computational fluid dynamics (CFD)-based model of drug dissolution, absorption and clearance occurring in the surface liquid of a representative small airway generation (G13) was developed and used to evaluate epithelial dose for the same deposited drug mass of conventional microparticles, nanoaggregates and a true nanoaerosol...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28639542/fluticasone-propionate-and-fluticasone-propionate-salmeterol-multidose-dry-powder-inhalers-compared-with-placebo-for-persistent-asthma
#3
L D Sher, G Yiu, A Sakov, S Liu, C F Caracta
BACKGROUND: A novel, inhalation-driven, multidose dry powder inhaler (MDPI) has been developed, which allows for lowerdoses of fluticasone propionate (Fp) and Fp/salmeterol (FS) for the treatment of patients with asthma. OBJECTIVE: This phase III, multicenter, double-blind, parallel-group study (NCT02141854) evaluated the efficacy and safetyof Fp MDPI and FS MDPI versus placebo MDPI. METHODS: Patients aged greater than or equal to 12 years with persistent asthma who previously took an inhaled corticosteroid with or without a long-acting beta-agonist entered a 14- to 21-day run-in period, during which they received single-blind, low-dose Fp MDPI 50 microgram (1 inhalation twice daily [b...
June 21, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28639121/montelukast-use-a-19-year-nationwide-drug-utilisation-study
#4
Daniel Pilsgaard Henriksen, Jesper Rømhild Davidsen, Christian B Laursen, Anders Christiansen, Per Damkier, Jesper Hallas, Anton Pottegård
PURPOSE: Montelukast is a leukotriene receptor antagonist used in asthma and rhinitis treatment. Despite being marketed nearly two decades ago, little is known about its utilisation pattern. METHODS: Using the Danish National Prescription Registry, we identified subjects filling a montelukast prescription between 1998 and 2017. Using descriptive statistics, we reported the development in incidence, and prevalence, as well as a measure of treatment duration, and concomitant use of asthma- or anti-allergic therapy...
June 22, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28638328/protocol-for-the-reconstructing-consciousness-and-cognition-reccognition-study
#5
Kaitlyn L Maier, Andrew R McKinstry-Wu, Ben Julian A Palanca, Vijay Tarnal, Stefanie Blain-Moraes, Mathias Basner, Michael S Avidan, George A Mashour, Max B Kelz
Important scientific and clinical questions persist about general anesthesia despite the ubiquitous clinical use of anesthetic drugs in humans since their discovery. For example, it is not known how the brain reconstitutes consciousness and cognition after the profound functional perturbation of the anesthetized state, nor has a specific pattern of functional recovery been characterized. To date, there has been a lack of detailed investigation into rates of recovery and the potential orderly return of attention, sensorimotor function, memory, reasoning and logic, abstract thinking, and processing speed...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28637216/qualitative-analysis-and-detection-of-the-pyrolytic-products-of-jwh-018-and-11-additional-synthetic-cannabinoids-in-the-presence-of-common-herbal-smoking-substrates
#6
Stephen Raso, Suzanne Bell
Synthetic cannabinoids have become a ubiquitous challenge in forensic toxicology and seized drug analysis. Thermal degradation products have yet to be identified and evaluated for toxicity in comparison to parent and metabolic compounds. An investigation into these pyrolytic products, as the major route of ingestion is inhalation, may produce additional insight to understand the toxicity of synthetic cannabinoids. The pyrolysis of JWH-018 and 11 additional synthetic cannabinoids and six herbal plant substrates were conducted using an in-house constructed smoking simulator...
June 20, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28631599/efficacy-and-safety-of-omalizumab-in-children-and-adolescents-with-moderate-to-severe-asthma-a-systematic-literature-review
#7
J Corren, A Kavati, B Ortiz, J A Colby, K Ruiz, B A Maiese, S M Cadarette, R A Panettieri
BACKGROUND: There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety ofomalizumab in the real-world management of allergic asthma. OBJECTIVE: The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinicaltrials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma. METHODS: Studies that evaluated omalizumab use in patients < 18 years old and with asthma, published between January2003 and October 2016, were retrieved from medical literature data bases...
June 19, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28631111/suffocation-caused-by-plastic-wrap-covering-the-face-combined-with-nitrous-oxide-inhalation
#8
Peter Mygind Leth, Birgitte Schmidt Astrup
Suicide using a combination of a plastic bag over the head and inhalation of a non-irritating gas, such as helium, argon or nitrogen, has been reported in the literature. Here an unusual suicide method in a 17-year old man by suffocation from covering the face with household plastic wrap, combined with nitrous oxide inhalation, is presented. The case was reviewed based on police, autopsy and hospital reports. A PubMed search for scientific literature related to nitrous oxide abuse and suicide by suffocation was performed and our findings discussed in relation to the scientific literature found...
June 19, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28629803/development-of-mpc-dpa-polymeric-nanoparticle-systems-for-inhalation-drug-delivery-applications
#9
Abdul Khaliq Elzhry Elyafi, Guy Standen, Steven T Meikle, Andrew L Lewis, Jonathan P Salvage
Inhalation of nanoparticles for pulmonary drug delivery offers the potential to harness nanomedicine formulations of emerging therapeutics, such as curcumin, for treatment of lung cancer. Biocompatible nanoparticles composed of poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) have been shown to be suitable nanocarriers for drugs, whilst N-trimethyl chitosan chloride (TMC) coating of nanoparticles has been reported to further enhance their cellular delivery efficacy; the combination of the two has not been previously investigated...
June 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28629719/alpha-ketoglutarate-nanoparticles-a-potentially-effective-treatment-for-cyanide-poisoning
#10
Shaheen Sultana, Sushma Talegaonkar, Dhruv Kumar Nishad, Gaurav Mittal, F J Ahmad, Aseem Bhatnagar
The purpose of this research work was to prepare nanosized formulation of alpha ketoglutarate as dry powder inhaler for cyanide poisoning. Nanosizing can be approached by solid phase and liquid phase method. The different conditions encountered in both these approaches can greatly affect the particle characteristics. In this study milling and precipitation technique were compared to study their effect on α-KG particles characteristics. Differences in choice of stabilizers were observed between the two processing techniques...
June 16, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28626631/chronic-eosinophilic-pneumonia-adjunctive-therapy-with-inhaled-steroids
#11
Christopher Chan, David DeLapp, Perry Nystrom
Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare form of diffuse parenchymal lung disease first identified by Carrington et al. in 1969. It is characterized by the presence of constitutional and respiratory symptoms with associated peripheral opacities on imaging and elevated serum and/or bronchoalveolar eosinophilia. Although data is limited regarding etiology or prevalence, it is known that ICEP has a 2:1 female: male predominance and typically affects non-smokers. Diagnosis rests on the clinical constellation of respiratory symptoms of at least 2-4 weeks duration, the presence of diffuse pulmonary alveolar consolidation, classically described as the "photographic negative of pulmonary edema", the presence of eosinophils ≥40% on bronchoalveolar lavage or ≥1000/mm(3) eosinophils on peripheral blood and the exclusion of other known causes of eosinophilic lung diseases such as drugs, toxins, fungi, parasites, and collagen-vascular disorders...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28626506/impact-of-nonadherence-to-inhaled-corticosteroid-laba-therapy-on-copd-exacerbation-rates-and-healthcare-costs-in-a-commercially-insured-us-population
#12
Jill R Davis, Bingcao Wu, David M Kern, Ozgur Tunceli, Kathleen M Fox, John Horton, Randall F Legg, Frank Trudo
BACKGROUND: Evidence of poor patient adherence to medications for chronic obstructive pulmonary disease (COPD) is well-documented, but its impact on disease exacerbation rates and associated healthcare costs remains unclear. OBJECTIVE: To assess the association between adherence levels to different inhaled corticosteroid/long-acting ß2-adrenergic agonist (LABA) and COPD exacerbation rates and costs in a commercially insured population. METHODS: In this observational cohort study, patients with COPD (aged ≥40 years) who were treatment-naïve to inhaled corticosteroid/LABA and were initiating budesonide plus formoterol or fluticasone plus salmeterol between March 1, 2009, and January 31, 2014, were identified in a national representative claims database and were followed for up to 12 months...
April 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28626480/development-of-dry-powder-inhaler-containing-tadalafil-loaded-plga-nanoparticles
#13
Jaleh Varshosaz, Somayeh Taymouri, Hamed Hamishehkar, Razieh Vatankhah, Shadi Yaghubi
Inhalable dry powders containing poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were developed for the delivery of tadalafil (TAD) for treatment of life-treating pulmonary arterial hypertension. Taguchi design was employed to evaluate the effects of different formulation variables on the physicochemical characteristics of PLGA-NPs prepared using emulsion solvent evaporation method. Inhalable PLGA-NPs of TAD were successfully prepared by co-spray drying the PLGA-NPs with inert carriers. Physicochemical characteristics and in vitro deposition of the aerosolized drug were also evaluated...
June 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28624659/surface-engineering-of-solid-lipid-nanoparticle-assemblies-by-methyl-%C3%AE-d-mannopyranoside-for-the-active-targeting-to-macrophages-in-anti-tuberculosis-inhalation-therapy
#14
Eleonora Maretti, Luca Costantino, Cecilia Rustichelli, Eliana Leo, Maria Antonietta Croce, Francesca Buttini, Eleonora Truzzi, Valentina Iannuccelli
This study describes the development of new mannosylated Solid Lipid Nanoparticle assemblies (SLNas) delivering rifampicin for an inhaled treatment of tuberculosis. SLNas were surface engineered with mannose residues to recognize mannose receptors located on infected alveolar macrophages and facilitate cell internalization. Two sets of SLNas were produced by the melt emulsifying technique using biocompatible lipid components, i.e. cholesteryl myristate combined with palmitic acid (PA set) or tripalmitin (TP set), in the presence of the targeting moiety, methyl α-d-mannopyranoside...
June 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28621369/transport-of-nanoparticles-across-pulmonary-surfactant-monolayer-a-molecular-dynamics-study
#15
Yan Xu, Li Deng, Hao Ren, Xianren Zhang, Fang Huang, Tongtao Yue
Pulmonary nanodrug delivery is an emerging concept, especially for targeted lung cancer therapy. Once inhaled, the nanoparticles (NPs) acting as drug carriers need to efficiently cross the pulmonary surfactant monolayer (PSM) of lung alveoli, which act as the first barrier for external particles entering the lung. Herein, by performing molecular dynamics simulations, we study how inhaled NPs interact with the PSM, particularly focusing on the transport of NPs with different properties across the PSM. While hydrophilic NPs translocate directly across the PSM, transport of hydrophobic NPs is achieved as the PSM wraps them...
June 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28619456/how-does-secondary-processing-affect-the-physicochemical-properties-of-inhalable-salbutamol-sulphate-particles-a-temporal-investigation
#16
Joana T Pinto, Snezana Radivojev, Sarah Zellnitz, Eva Roblegg, Amrit Paudel
As pulmonary drug delivery is extended from low doses to high doses, physicochemical characteristics of the active pharmaceutical ingredient gain importance in the development of dry powder inhalers. Therefore, the present work aims to understand the impact of distinct engineering techniques on the process induced physicochemical characteristics of salbutamol sulphate particles over time. The particle engineering techniques chosen were jet-milling and spray-drying, two well used processes in the production of predominately crystalline and amorphous inhalable particles, respectively...
June 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28616347/intraoperative-care-for-aortic-surgery-using-circulatory-arrest
#17
REVIEW
Félix Ezequiel Fernández Suárez, David Fernández Del Valle, Adrián González Alvarez, Blanca Pérez-Lozano
The total circulatory arrest (CA) is necessary to achieve optimal surgical conditions in certain aortic pathologies, especially in those affecting the ascending aorta and aortic arch. During this procedure it is necessary to protect all the organs of ischemia, especially those of the central nervous system and for this purpose several strategies have been developed. The first and most important protective method is systemic hypothermia. The degree of hypothermia and the route of application have been evolving and currently tend to use moderate hypothermia (MH) (20...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28612675/formulation-of-novel-dry-powder-inhalation-for-fluticasone-propionate-and-salmeterol-xinafoate-with-capsule-based-device
#18
Kyeong Soo Kim, Jeong Hyun Kim, Sung Giu Jin, Dong Wuk Kim, Jong Oh Kim, Chul Soon Yong, Yu Seok Youn, Kyung Taek Oh, Jong Soo Woo, Han-Gon Choi
The aim of this study was to develop a novel fluticasone propionate (FP) and salmeterol xinafoate (SX)-loaded dry powder inhaler (DPI) system, which was composed of powder formulation and performance. The air flow resistances were determined with various types of DPI device, showing that the modified RS01 device gave the specific resistance similar to the commercial DPI device. The particle properties of fluticasone propionate (FP), salmeterol xinafoate (SX) and inhalation grade lactose particles, such as particle size, size distribution and fine content, were assessed...
June 14, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/28604098/nitrous-oxide-and-midazolam-sedation-a-systematic-review-and-meta-analysis
#19
Gowri Sivaramakrishnan, Kannan Sridharan
Nitrous oxide and midazolam have been used as sedative agents to decrease fear and anxiety associated with dental procedures. Although these agents have been widely used individually, the combination of the two is also commonly used. Four clinical trials were identified that compared the combination technique with the individual use of the drugs. The standardized mean difference (SMD) for each outcome measure was considered for final analysis. Three studies with 534 participants were included in the final meta-analysis, and the SMD [95% CI] was obtained as -0...
2017: Anesthesia Progress
https://www.readbyqxmd.com/read/28602990/enhancement-in-in-vitro-anti-angiogenesis-activity-and-cytotoxicity-in-lung-cancer-cell-by-pectin-pvp-based-curcumin-particulates
#20
Dinanath Gaikwad
The aim of this work was to prepare pectin-poly (vinyl pyrrolidone) [PVP] based curcumin particulates to enhance the anticancer potential of curcumin, solubility and allow its localized controlled release. Pectin-PVP based curcumin particulates (PECTIN-PVP CUR) were prepared by spray drying technique in different ratios and were evaluated for surface morphology, micromeritics, flowability, particle size, drug content, in vitro dissolution, inhalable fraction, anti-angiogenesis/angiolysis and cytotoxicity. Results of micromeritic properties, Carr's index, Hausner's ratio and angle of repose were satisfactory...
June 8, 2017: International Journal of Biological Macromolecules
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