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：:(13) C cross-polarization magic-angle spinning nuclear magnetic resonance (CPMAS NMR) spectroscopy was applied to the identification and characterization of carvedilol (1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)-ethylamino]-propan-2-ol) in pharmaceutical preparations. Solid-state spectra (standard linewidth and l...
journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600740329
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abstract：:An automated, stability-indicating, UV spectrophotometric assay for cefazolin is presented. The method employs a reaction with hydroxylamine and derives its stability-indicating power through comparison of reacted and unreacted aliquots of the sample. A double-probe sampling procedure is used. Good agreement with micr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640725
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abstract：:Drying is a common pharmaceutical process, whose potential to modify the final drug and/or dosage form properties is often underestimated. In the present study, pellets consisting of the matrix former calcium stearate (CaSt) incorporating the active pharmaceutical ingredient ibuprofen were prepared via wet extrusion a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23707
更新日期：2013-11-01 00:00:00
abstract：:The area under the plasma concentration-time curve (AUC) was measured after an intravenous injection of sodium salicylate and after intragastric administration of aspirin, using either an intermittent sampling and the trapezoid rule (AUC-trapezoid) or the recently introduced constant blood withdrawal method (AUC-integ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670644
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abstract：:A new, specific, and useful approach for the analysis of benzalkonium chloride is presented. Reversed-phase high-pressure liquid chromatography is used to determine benzalkonium chloride in an ophthalmic system at the presevative level of 0.004%. Since the method separates each homolog, it can be extended to determine...
journal_title：Journal of pharmaceutical sciences
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abstract：:In our previous research, cocaine applied intranasally in rats diffused or was transported directly from the nasal cavity to the brain. However, the direct nose-brain cocaine transport only contributes to an initial increase in the relative cocaine brain exposure. In this study, we have determined the nose-brain trans...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1122
更新日期：2001-11-01 00:00:00
abstract：:A series of substituted 3-(benzylideneamino) coumarins was synthesized and evaluated for anti-inflammatory activity against carrageenan-induced edema in rats. Halogenated derivatives 4g and 4c, at oral doses of 100 mg/kg, showed 75 and 60% antiedmatous activity, respectively (phenylbutazone antiedematous activity, 58%...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600810926
更新日期：1992-09-01 00:00:00
abstract：:In this study, the effects of structurally related organic impurities on the molecular dynamics of amorphous sulfamethazine were evaluated using thermal analysis. Sulfanilamide (SNA), sulfamerazine (SMR), and sulfadimethoxine were used as virtual impurities of sulfamethazine. The amorphous state was prepared in situ i...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2016.12.008
更新日期：2017-04-01 00:00:00
abstract：:Sugars and polyols have been used routinely with lyophilized proteins and peptides as bulking agents, cryoprotectants, and lyoprotectants. However, reducing sugars may present a problem as excipients since they are potentially reactive with proteins. In this stability study of recombinant human relaxin (Rix) with vari...
journal_title：Journal of pharmaceutical sciences
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doi：10.1021/js950456s
更新日期：1996-08-01 00:00:00
abstract：:The aim of this article was to prepare a topical powder for the treatment of fungal infections, such as Candida intertrigo and tinea pedis. Thus, an econazole nitrate (ECO) formulation with improved drug dissolution and proper moisture adsorption was designed. ECO was melt with the mesoporous silicate MCM-41 (drug/MCM...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.22183
更新日期：2010-11-01 00:00:00
abstract：:Acetylcarnitine, a naturally occurring compound found in high concentration in heart and skeletal muscle of vertebrates, bears structural resemblance to acetylcholine, and studies have shown that it has slight cholinergic properties. Acetylcarnitine was subjected to conformational analysis by extended Hückel theory (E...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690921
更新日期：1980-09-01 00:00:00
abstract：:The aim of this review is to describe the theoretical background lying behind the solid drug mechanochemical activation by cogrinding pointing out its advantages and drawbacks. A brief historical introduction precedes the discussion about the mechanisms leading to solid drug activation. This allows to clarify the conc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.21733
更新日期：2009-11-01 00:00:00
abstract：:This work compares the conformational stability, backbone flexibility, and aggregation propensity of monomer and dimer fractions of an IgG1 monoclonal antibody (mAb) generated on UVA light exposure for up to 72 h collected by preparative size-exclusion chromatography, compared with unstressed control. UVA light exposu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.01.017
更新日期：2018-06-01 00:00:00
abstract：:The insidious nature of Zika virus (ZIKV) infections can have a devastating consequence for fetal development. Recent reports have highlighted that chloroquine (CQ) is capable of inhibiting ZIKV endocytosis in brain cells. We applied pharmacokinetic modeling to develop a predictive model for CQ exposure to identify an...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2018.10.056
更新日期：2019-01-01 00:00:00
abstract：:There is a growing interest in developing inhibitors of the neonatal Fc-receptor, FcRn, for use in the treatment for humoral autoimmune conditions. We have developed a new physiologically based pharmacokinetic model that is capable of characterizing the pharmacokinetics and pharmacodynamics of anti-FcRn monoclonal ant...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2018.10.065
更新日期：2019-01-01 00:00:00
abstract：:The in vitro binding of warfarin by human serum albumin was studied at various temperatures and at pH 7.4 by a frontal gel filtration technique. The results can be best described in terms of a two class-of-binding site model, in which the numbers of primary and secondary sites are constrained to the average values for...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600651127
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abstract：:Peptidomimetic drugs have favorable bioavailability owing to H(+)/peptide transporter 1 (PEPT1) located in the intestine. Sartans are commonly used and likely coadministered with peptidomimetic drugs in the clinic; however, in vivo interactions between sartans and peptidomimetic drugs have not been systemically unders...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.23805
更新日期：2014-02-01 00:00:00
abstract：:To evaluate oral mucosal absorption of drugs in dogs, a newly designed in situ perfusion system with a circulating perfusion chamber was developed. The utility of the perfusion system was investigated by using three drugs: salicylic acid (SA), sulfadimethoxine (SM), and diltiazem (DIL). The oral mucosal absorption of ...
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abstract：:Two multisample laboratory powder diffractometers have been evaluated for the purpose of pattern indexing in the context of physical form screening. Both diffractometers utilise foil transmission geometry, primary monochromated radiation, and a position-sensitive detector. Data collected from six compounds (sotalol hy...
journal_title：Journal of pharmaceutical sciences
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abstract：:The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free a...
journal_title：Journal of pharmaceutical sciences
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更新日期：2018-02-01 00:00:00
abstract：:The aim of this study is to explore hot melt extrusion (HME) as a solvent-free drug loading technique for preparation of stable amorphous solid dispersions using mesoporous silica (PSi). Ibuprofen and carvedilol were used as poorly soluble active pharmaceutical ingredients (APIs). Due to the high friction of an API:PS...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2017.05.039
更新日期：2018-01-01 00:00:00
abstract：:The reaction of UICEL-A/102, a cellulose II powder recently prepared from Avicel(R) PH-102 by treatment with an aqueous sodium hydroxide solution, with glutaraldehyde in 0.01 N HCl has been investigated to improve its binder properties, without adversely affecting the rapid disintegration characteristic. The results s...
journal_title：Journal of pharmaceutical sciences
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更新日期：2007-02-01 00:00:00
abstract：:The release kinetics of a polymeric-controlled release device are determined by its geometry and dimensions. A method to calculate the required size and shape of diffusion-controlled dosage forms to achieve a particular release profile is presented. The diffusion parameters are determined for various drugs (theophylli...
journal_title：Journal of pharmaceutical sciences
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更新日期：1998-07-01 00:00:00
abstract：:The ability to produce and isolate relatively pure amounts of relevant degradation products is key to several aspects of drug product development: (a) aid in the unambiguous structural identification of such degradation products, fulfilling regulatory requirements to develop safe formulations (International Conference...
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更新日期：2019-04-01 00:00:00
abstract：:We have shown that adsorbability of local anesthetics onto activated carbon, expressed by the partition coefficients at infinite dilution, correlated well with the pharmacological activity. However, there is no parameter that can singly express the tendency to be adsorbed. Adsorbability is a loosely defined term and i...
journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20071
更新日期：2004-06-01 00:00:00
abstract：:For development and optimization of protein formulation sensitive analytical tools are required to follow both aggregation and changes in protein structure. The latter can be seen as the beginning of physical instability leading to aggregation. The focus of this work laid on the development of a novel analysis simulta...
journal_title：Journal of pharmaceutical sciences
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更新日期：2012-02-01 00:00:00
abstract：:Homologous series of L-methionine alkyl ester hydrochlorides and tosylates were synthesized and evaluated for in vitro growth inhibitory activity in Meth A sarcoma. Cytotoxicity, as determined by [3H]thymidine incorporation, was found to be directly proportional to alkyl chain length and surface tension lowering activ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780609
更新日期：1989-06-01 00:00:00
