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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/28638167/computational-fluid-dynamics-analysis-of-the-venturi-dustiness-tester
#2
Prahit Dubey, Urmila Ghia, Leonid A Turkevich
Dustiness quantifies the propensity of a finely divided solid to be aerosolized by a prescribed mechanical stimulus. Dustiness is relevant wherever powders are mixed, transferred or handled, and is important in the control of hazardous exposures and the prevention of dust explosions and product loss. Limited quantities of active pharmaceutical powders available for testing led to the development (at University of North Carolina) of a Venturi-driven dustiness tester. The powder is turbulently injected at high speed (Re ~ 2 × 10(4)) into a glass chamber; the aerosol is then gently sampled (Re ~ 2 × 10(3)) through two filters located at the top of the chamber; the dustiness index is the ratio of sampled to injected mass of powder...
May 2017: Powder Technology
https://www.readbyqxmd.com/read/28632895/genome-mining-reveals-high-incidence-of-putative-lipopeptide-biosynthesis-nrps-pks-clusters-containing-fatty-acyl-amp-ligase-genes-in-biofilm-forming-cyanobacteria
#3
Tomáš Galica, Pavel Hrouzek, Jan Mareš
Cyanobacterial lipopeptides exhibit antimicrobial and antifungal bioactivities with potential for use in pharmaceutical research. However, due to their haemolytic activity and cytotoxic effects against human cells, they may pose a health issue if produced in substantial amounts in the environment. In bacteria, lipopeptides can be synthesized via several well-evidenced mechanisms. In one of them, fatty acyl-AMP ligase (FAAL) initiates the biosynthesis by activation of a fatty acyl residue. We have performed a bioinformatic survey of the cyanobacterial genomic information available in the public databases for the presence of FAAL-containing non-ribosomal peptide synthetase/polyketide synthetase (NRPS/PKS) biosynthetic clusters, as a genetic basis for lipopeptide biosynthesis...
June 20, 2017: Journal of Phycology
https://www.readbyqxmd.com/read/28628923/cremophor-el-alters-the-plasma-protein-binding-and-pharmacokinetic-profile-of-valspodar-in-rats
#4
Ziyad Binkhathlan
Cremophor EL is a nonionic surfactant widely used in pharmaceutical formulations. Nonetheless, there are several reports on the influence of this excipient on the protein binding, pharmacokinetics, and pharmacodynamics of drugs. Valspodar is an investigational non-immunosuppressive derivative of cyclosporine A, used in clinical trials for treatment of multidrug resistant tumors. The formulation of valspodar (Amdray(®)) contains cremophor EL and ethanol as solubilizing agents. The main aim of the current study was to assess the plasma protein binding (in vitro) and the pharmacokinetic profile of valspodar in the cremophor EL-based formulation in comparison to a cremophor EL-free formulation following intravenous (i...
June 19, 2017: Drug Research
https://www.readbyqxmd.com/read/28628716/imprinted-photonic-hydrogels-for-the-size-and-shell-selective-recognition-of-nanoparticles
#5
Sarra Gam-Derouich, Céline Bourdillon, Soraya Lakhdar Chaouche, Laurent Coolen, Agnès Maître, Claire Mangeney, Catherine Schwob
Sensors based on responsive photonic hydrogels have recently attracted considerable attention for visual medical diagnostics, pharmaceutical bioassays and environmental monitoring. However, the use of these promising materials for the detection of nanoparticles (NPs) has never been explored so far, although the sensing of nano-objects is a rapidly-evolving new area of research. To address this issue, we have combined the concepts of inverse opal hydrogels and nanoparticle-imprinted polymers. By this way, we could obtain a NP-imprinted photonic hydrogel, consisting in a three-dimensional, highly-ordered poly(methacrylic acid) macroporous array, where nanocavities complementary to the target NPs, here colloidal quantum dots, are distributed...
June 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28627457/analysis-of-the-origins-of-content-non-uniformity-in-high-shear-wet-granulation
#6
Sarang Oka, David Smrčka, Anjali Kataria, Heather Emady, Fernando Muzzio, František Štěpánek, Rohit Ramachandran
In this study, the origins of granule content non-uniformity in the high-shear wet granulation of a model two-component pharmaceutical blend were investigated. Using acetaminophen as the active pharmaceutical ingredient (API) and microcrystalline cellulose as the excipient, the distribution of the API across the granule size classes was measured for a range of conditions that differed in the duration of the initial dry mixing stage, the overall composition of the blend and the wet massing time. The coarse granule fractions were found to be systematically sub-potent, while the fines were enriched in the API...
June 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28619456/how-does-secondary-processing-affect-the-physicochemical-properties-of-inhalable-salbutamol-sulphate-particles-a-temporal-investigation
#7
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/28612675/formulation-of-novel-dry-powder-inhalation-for-fluticasone-propionate-and-salmeterol-xinafoate-with-capsule-based-device
#8
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/28611009/comprehensive-study-of-the-drug-delivery-properties-of-poly-l-lactide-poly-ethylene-glycol-nanoparticles-in-rats-and-tumor-bearing-mice
#9
Vladimir Shalgunov, Daria Zaytseva-Zotova, Arkady Zinchenko, Tatiana Levada, Yuri Shilov, Dmitry Andreyev, Dzhangar Dzhumashev, Evgeny Metelkin, Alexandra Urusova, Oleg Demin, Kevin McDonnell, Greg Troiano, Stephen Zale, Elmira Safarovа
Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice...
June 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28609624/in-silico-absorption-distribution-metabolism-excretion-and-pharmacokinetics-adme-pk-utility-and-best-practices-an-industry-perspective-from-the-international-consortium-for-innovation-through-quality-in-pharmaceutical-development
#10
Franco Lombardo, Prashant V Desai, Rieko Arimoto, Kelly E Desino, Holger Fischer, Christopher E Keefer, Carl Petersson, Susanne Winiwarter, Fabio Broccatelli
In silico tools to investigate absorption, distribution, metabolism, excretion and pharmacokinetics (ADME-PK) properties of new chemical entities are an integral part of the current industrial drug discovery paradigm. While many companies are active in the field, scientists engaged in this area don't necessarily share the same background and have limited resources when seeking guidance on how to initiate and maintain an in silico ADME-PK infrastructure in an industrial setting. This work summarizes the views of a group of industrial in silico and experimental ADME scientists, participating in the In Silico ADME Working Group, a subgroup of the International Consortium for Innovation through Quality in Pharmaceutical Development (IQ) Drug Metabolism Leadership Group...
June 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28604616/legume-lectins-proteins-with-diverse-applications
#11
REVIEW
Irlanda Lagarda-Diaz, Ana Maria Guzman-Partida, Luz Vazquez-Moreno
Lectins are a diverse class of proteins distributed extensively in nature. Among these proteins; legume lectins display a variety of interesting features including antimicrobial; insecticidal and antitumor activities. Because lectins recognize and bind to specific glycoconjugates present on the surface of cells and intracellular structures; they can serve as potential target molecules for developing practical applications in the fields of food; agriculture; health and pharmaceutical research. This review presents the current knowledge of the main structural characteristics of legume lectins and the relationship of structure to the exhibited specificities; provides an overview of their particular antimicrobial; insecticidal and antitumor biological activities and describes possible applications based on the pattern of recognized glyco-targets...
June 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28603959/characterization-of-complex-polymer-self-assemblies-and-large-aggregates-by-multidetector-thermal-field-flow-fractionation
#12
Upenyu L Muza, Guilaume Greyling, Harald Pasch
Micelles prepared from amphiphilic block copolymers (ABCs) have found numerous applications in pharmaceutical, electronics, environmental, cosmetics, and hygiene industries. These micelles, whether in the pure or mixed micelle form, often exist as multiple morphologies (spherical, cylindrical, worm, or vesicular) in equilibrium with each other. However, none of the current column-based fractionation techniques or any microscopic technique are capable of a successful separation, identification, and quantitation of these complex self-assemblies with regards to morphology, size, molar mass, and chemical composition in one experiment...
June 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28603030/nanosizing-techniques-for-improving-bioavailability-of-drugs
#13
REVIEW
Raida Al-Kassas, Mahima Bansal, John Shaw
The poor solubility of significant number of Active Pharmaceutical Ingredients (APIs) has become a major challenge in the drug development process. Drugs with poor solubility are difficult to formulate by conventional methods and often show poor bioavailability. In the last decade, attention has been focused on developing nanocrystals for poorly water soluble drugs using nanosizing techniques. Nanosizing is a pharmaceutical process that changes the size of a drug to the sub-micron range in an attempt to increase its surface area and consequently its dissolution rate and bioavailability...
June 8, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28603020/hot-melt-extrusion-hme-as-solvent-free-technique-for-a-continuous-manufacturing-of-drug-loaded-mesoporous-silica
#14
Natalja Genina, Batol Hadi, Korbinian Löbmann
The aim of the study was to explore hot melt extrusion (HME) as a solvent-free drug loading technique for preparation of stable amorphous solid dispersions (ASD) using mesoporous silica (PSi). Ibuprofen (IBU) and carvedilol (CAR) were used as poorly soluble active pharmaceutical ingredients (APIs). Due to the high friction of a API: PSi mixture below the loading limit of the API, it was necessary to add the polymer Soluplus(®) (SOL) in order to enable the extrusion process. As a result the APIs distributed between the PSi and SOL phase after HME...
June 8, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28596141/delivery-of-cyclodextrin-polymers-to-bacterial-biofilms-an-exploratory-study-using-rhodamine-labelled-cyclodextrins-and-multiphoton-microscopy
#15
Hanna Thomsen, Gábor Benkovics, Éva Fenyvesi, Anne Farewell, Milo Malanga, Marica B Ericson
Cyclodextrin (CD) polymers are interesting nanoparticulate systems for pharmaceutical delivery; however, knowledge regarding their applications towards delivery into complex microbial biofilm structures is so far limited. The challenge is to demonstrate penetration and transport through the biofilm and its exopolysaccharide matrix. The ideal functionalization for penetration into mature biofilms is unexplored. In this paper, we present a novel set of rhodamine labelled βCD-polymers, with different charge moieties, i...
June 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28595064/a-means-of-improving-public-health-in-low-and-middle-income-countries-benefits-and-challenges-of-international-public-private-partnerships
#16
REVIEW
L Kostyak, D M Shaw, B Elger, B Annaheim
OBJECTIVE: In the last two decades international public-private partnerships have become increasingly important to improving public health in low- and middle-income countries. Governments realize that involving the private sector in projects for financing, innovation, development, and distribution can make a valuable contribution to overcoming major health challenges. Private-public partnerships for health can generate numerous benefits but may also raise some concerns. To guide best practice for public-private partnerships for health to maximize benefits and minimize risks, the first step is to identify potential benefits, challenges, and motives...
June 5, 2017: Public Health
https://www.readbyqxmd.com/read/28593506/conformal-mapping-of-carotid-vessel-wall-and-plaque-thickness-measured-from-3d-ultrasound-images
#17
Gary P T Choi, Yimin Chen, Lok Ming Lui, Bernard Chiu
Measurements of vessel-wall-plus-plaque thickness (VWT) from 3D carotid ultrasound have been shown to be sensitive to the effect of pharmaceutical interventions. Since the geometry of carotid arteries is highly subject-specific, quantitative comparison of the distributions of point-wise VWT measured for different patients or for the same patients at different ultrasound scanning sessions requires the development of a mapping strategy to adjust for the geometric variability of different carotid surface models...
June 7, 2017: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/28590391/misuse-of-novel-synthetic-opioids-a-deadly-new-trend
#18
Matthew P Prekupec, Peter A Mansky, Michael H Baumann
: Novel synthetic opioids (NSOs) include various analogs of fentanyl and newly emerging non-fentanyl compounds. Together with illicitly manufactured fentanyl (IMF), these drugs have caused a recent spike in overdose deaths, whereas deaths from prescription opioids have stabilized. NSOs are used as stand-alone products, as adulterants in heroin, or as constituents of counterfeit prescription medications. During 2015 alone, there were 9580 deaths from synthetic opioids other than methadone. Most of these fatalities were associated with IMF rather than diverted pharmaceutical fentanyl...
June 5, 2017: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/28589305/discriminating-ability-of-abbreviated-impactor-measurement-approach-aim-to-detect-changes-in-mass-median-aerodynamic-diameter-mmad-of-an-albuterol-salbutamol-pmdi-aerosol
#19
J David Christopher, Rajni B Patel, Jolyon P Mitchell, Terrence P Tougas, Adrian P Goodey, Jorge Quiroz, Patrik U Andersson, Svetlana Lyapustina
This article reports on results from a two-lab, multiple impactor experiment evaluating the abbreviated impactor measurement (AIM) concept, conducted by the Cascade Impaction Working Group of the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of this experiment was to expand understanding of the performance of an AIM-type apparatus based on the Andersen eight-stage non-viable cascade impactor (ACI) for the assessment of inhalation aerosols and sprays, compared with the full-resolution version of that impactor described in the pharmacopeial compendia...
June 6, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28589013/quality-assurance-of-medicines-supplied-to-low-income-and-middle-income-countries-poor-products-in-shiny-boxes
#20
A Nebot Giralt, B Schiavetti, B Meessen, C Pouget, J M Caudron, B Marchal, P Massat, S Thys, R Ravinetto
OBJECTIVE: In today's context of globalisation of pharmaceutical production and distribution, international and national procurement agencies play a de facto key role in defining the quality of medicines available in sub-Saharan Africa. We evaluated the compliance of a sample of pharmaceutical distributors active in sub-Saharan Africa with the standards of the WHO guideline 'Model Quality Assurance System (WHO MQAS) for procurement agencies', and we investigated factors favouring or hindering the adequate implementation of the guideline...
March 2017: BMJ Global Health
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