Abstract：
:The presence of subvisible particles in formulations of therapeutic proteins is a risk factor for adverse immune responses. Although the immunogenic potential of particulate contaminants likely depends on particle structural characteristics (e.g., composition, size, and shape), exact structure-immunogenicity relationships are unknown. Images recorded by flow imaging microscopy reflect information about particle morphology, but flow microscopy is typically used to determine only particle size distributions, neglecting information on particle morphological features that may be immunologically relevant. We recently developed computational techniques that utilize the Kullback-Leibler divergence and multidimensional scaling to compare the morphological properties of particles in sets of flow microscopy images. In the current work, we combined these techniques with expectation maximization cluster analyses and used them to compare flow imaging microscopy data sets that had been collected by the U.S. Food and Drug Administration after severe adverse drug reactions (including 7 fatalities) were observed in patients who had been administered some lots of peginesatide formulations. Flow microscopy images of particle populations found in the peginesatide lots associated with severe adverse reactions in patients were readily distinguishable from images of particles in lots where severe adverse reactions did not occur.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Daniels AL,Randolph TWdoi
10.1016/j.xphs.2018.01.015subject
Has Abstractpub_date
2018-05-01 00:00:00pages
1313-1321issue
5eissn
0022-3549issn
1520-6017pii
S0022-3549(18)30017-0journal_volume
107pub_type
杂志文章abstract：:The oral dose metabolism of dilazep dihydrochloride [tetrahydro-1H-1,4-diazepine-1,4(5H)-dipropanol 3,4,5-trimethoxybenzoate] was examined in six hypertensive patients receiving a single oral dose of 600 mg of dilazep (3-3.8 mg/kg BW). Blood was collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 h after administratio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780404
更新日期：1989-04-01 00:00:00
abstract：:A quantitative high-pressure liquid chromatographic method, using a reversed-phase column coupled to a fluorescence detector, was developed to determine salicylic acid in bulk aspirin and plain and buffered aspirin tablets. The aspirin was dissolved, filtered, and injected into the chromatograph; the fluorescence of t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690518
更新日期：1980-05-01 00:00:00
abstract：:TLC analysis of extracts of Pilosocereus maxonii (Rose) Byles and Rowley detected six identifiable alkaloids. Preparative TLC aided in the crystallization of the hydrochlorides of N-methyl-3,4-dimethoxyphenethylamine, N-methyl-3-methoxytyramine, and N,N-dimethyl-3-methoxytyramine. Traces of 3,4-dimethoxyphenethylamine...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661037
更新日期：1977-10-01 00:00:00
abstract：:Amorphous dispersions provide an excellent way of increasing dissolution rates of poorly soluble drugs, but there may be concerns about stability. One way of assessing the stability of amorphous is the study of relaxation. In this study the relaxation at the surface of amorphous solid dispersions (SDs) was evaluated u...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21573
更新日期：2009-06-01 00:00:00
abstract：:Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine have been measured over a 2-year period under ambient conditions and under temperature and humidity stress. Hydralazine tablets are stable under ambient conditions, but the hydrazine level in an injectable formulation increased from 4.5 to 10 m...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720836
更新日期：1983-08-01 00:00:00
abstract：:Pharmaceutical scientists are often asked to assess the impact of modifications to the illumination in the manufacturing and product packaging environment on product quality. To assess the impact of switching light sources, four model compounds were exposed to standard fluorescent light, LED, and "yellow light" and th...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.07.020
更新日期：2020-11-01 00:00:00
abstract：:Lysosomes are acidic intracellular organelles that can extensively sequester basic lipophilic drugs due to pH and membrane partitioning, and therefore may significantly influence subcellular drug concentrations. Current in vitro methods for lysosomal drug sequestration evaluation typically lack the ability to accurate...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.05.026
更新日期：2020-09-01 00:00:00
abstract：:In this contribution, we present an analysis of the main parameters influencing the efficiency of the (1)H → (13)C multiple-contact cross-polarization nuclear magnetic resonance (NMR) experiment in the context of solid pharmaceutical materials. Using the optimum experimental conditions, quantitative (13)C NMR spectra ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.05.025
更新日期：2016-08-01 00:00:00
abstract：:Oxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20632
更新日期：2006-08-01 00:00:00
abstract：:The development of sustained-release lithium (Li) tablets, intended to release the active principle at a rate of 1.0 mM/h for 10 h, was undertaken. The parameters used for the control of the release were the glyceril palmite-stearate content, the carboxypolymethylene content, and the compression force. The experimenta...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600801103
更新日期：1991-11-01 00:00:00
abstract：:A continuous nonisothermal-isothermal method for stability prediction was developed. The approach yields all necessary parameters for prediction, including reaction order. The experimental procedure involves changing the temperature of the samples being studied until degradation is rapid enough to proceed at a conveni...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640826
更新日期：1975-08-01 00:00:00
abstract：:The ratio between ocular and systemic drug concentrations describes the relative safety of ophthalmic dosage forms of the same drug in terms of its systemic side effects. In this study, we evaluated the effects of epinephrine pretreatment and solution pH on the aqueous humor:plasma and iris-ciliary body:plasma ratios ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790808
更新日期：1990-08-01 00:00:00
abstract：:This paper describes the synthesis and characterization of cationic copolymers with different macromolecular architecture and drug delivery properties of the corresponding dexamethasone sodium phosphate (DSP)-loaded systems. Copolyelectrolytes comprising poly[2-(acryloyloxy)ethyl] trimethylammonium chloride (PAETMAC) ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24059
更新日期：2014-08-01 00:00:00
abstract：:A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism. For the in vitro studies, radiolabeled [14C]cholic acid was incubated with human stools both in aerobic and anaerobic c...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810310
更新日期：1992-03-01 00:00:00
abstract：:The thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K-303 K (29 °C-30 °C). The polymorphs FI and FII have been characterised by infrared spectros...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.07.022
更新日期：2020-11-01 00:00:00
abstract：:In this work, a novel risk-based methodology for lot release is proposed. Its objective is to assess the risk that a lot declared to have passed truly meets product specifications. The methodology consists of 3 parts: adaptive sample size determination, estimation of the probability that the product was within specifi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.011
更新日期：2020-02-01 00:00:00
abstract：:Near infrared (NIR) spectroscopy was used for quantitatively monitoring polymorph conversion of an active pharmaceutical ingredient (API) in wet granulation. The API under pharmaceutical development has two different polymorphs. Polymorph A is the stable form for drug development and polymorph B is the undesired form ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20501
更新日期：2005-12-01 00:00:00
abstract：:Water evaporation rates were measured from thin samples of a model layered structure of stratum corneum lipids with 32% water. A model with only free fatty acids present gave the lowest evaporation rates, while a model with only oleic acid gave values approximately 50% higher. Using the total lipid spectrum of stratum...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780808
更新日期：1989-08-01 00:00:00
abstract：:In this paper, we establish a mechanistic model for the prediction of amorphous solid dispersion (ASD) stability. The novel approach incorporates fundamental physical parameters, principally supersaturation, diffusivity, and interfacial energy, to model crystallization in ASDs accounting for both kinetic and thermodyn...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.08.006
更新日期：2020-08-18 00:00:00
abstract：:Hard gelatin capsule (HGC) shells are widely used to encapsulate drugs for oral delivery but are vulnerable to gelatin cross-linking, which can lead to slower and more variable in vitro dissolution rates. Adding proteolytic enzymes to the dissolution medium can attenuate these problems, but this complicates dissolutio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.08.009
更新日期：2018-12-01 00:00:00
abstract：:The aminoxyl (nitroxyl) labeled (2-chloroethyl)nitrosocarbamoyl (CNC) derivatives of amino acids, i.e., N-[[N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl]-A-(1-oxy-2,2,6,6- tetramethylpiperidin-4-yl)amides, A = glycyl (10a), A = L-alanyl (10b), A = L-valyl (10c), A = L-phenylalanyl (10d), were synthesized and evaluated ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830715
更新日期：1994-07-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.03.003
更新日期：2019-08-01 00:00:00
abstract：:A suspension of micronized prednisolone acetate was separated into four fractions by the technique of centrifugal elutriation. Data showed that each fraction had a narrow particle size. The dissolution experiments were carried out under sink conditions (less than 10% of saturation concentration) in a dissolution appar...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720225
更新日期：1983-02-01 00:00:00
abstract：:Cytochrome P450 1B1 (CYP1B1) has been reported to have a major role in metabolizing arachidonic acid (AA) into cardiotoxic metabolites, mid-chain hydroxyeicosatetraenoic acids (HETEs). Recently, we have shown that fluconazole decreases the level of mid-chain HETEs in human liver microsomes. Therefore, the objectives o...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.03.016
更新日期：2020-07-01 00:00:00
abstract：:To study the effect of substituents on the antitumor activities of analogs of 1-phenyl-3-benzyl-3-methyltriazenes, a series of compounds was designed and synthesized in which the substituent on the 1-phenyl was an electron-withdrawing group and the substituent on the 3-benzyl had a broad range of physicochemical prope...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661017
更新日期：1977-10-01 00:00:00
abstract：:Gelrite, a heteropolysaccharide that forms a gel in the presence of cations, was tested in humans for its efficacy as an ophthalmic vehicle by a nonivasive fluorometric technique. Fluorescein was used as the tracer, and its concentration in the anterior chamber was used as the principal measure of bioavailability. The...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810704
更新日期：1992-07-01 00:00:00
abstract：:This work establishes a predictive model that explicitly recognizes microstructural parameters in the description of the overall mass uptake and local gradients of moisture into tablets. Model equations were formulated based on local tablet geometry to describe the transient uptake of moisture. An analytical solution ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.05.030
更新日期：2016-08-01 00:00:00
abstract：:A rapid, precise, and accurate high-performance liquid chromatographic procedure is presented for the stimultaneous determination of amitriptyline hydrochloride and chlordiazepoxide in two-component tablet formulations. The impurities and decomposition products of both components were separated, making the determinati...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690204
更新日期：1980-02-01 00:00:00
abstract：:Accurate partition coefficients K = Corg/Caq in chloroform-ammonia can be obtained by measuring the absorbance of the aqueous layer, replenishing with fresh aqueous solvent, and remeasuring the absorption after reequilibration. Provided the solute has a reasonably strong UV absorption, only 0.1-5 mg of material is req...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730222
更新日期：1984-02-01 00:00:00
abstract：:Mycophenolate mofetil (MPM), a new immunosuppressant, is the morpholinoethyl ester of mycophenolic acid (MPA). The distribution in blood and pharmacokinetics of MPA after administration of MPM were examined. The plasma to erythrocyte concentration ratio was low (0.10-0.15). MPA existed in rat plasma as the highly boun...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9502480
更新日期：1996-03-01 00:00:00
