Abstract：
:To reduce the risk of immunogenicity that may be caused by therapeutic protein products, it is important to properly characterize subvisible particles and to develop strategies to reduce the levels of particles delivered to patients. In the present study, by using state-of-the-art methods to quantify particle levels, we found that the factor VIII product, Kogenate FS, contained relatively high levels of protein particles and silicone oil droplets, the vast majority of which were submicron in size. In a test of effects of product mishandling, the Kogenate FS vial was shaken instead of swirled during reconstitution. Levels of silicone oil droplets and protein particles were increased. In contrast, these levels were greatly reduced by 2 mitigation strategies tested, using a nonsiliconized syringe for the diluent container or using submicron pore size syringe filters during simulated infusion. Thus, to avoid potential adverse effects due to mishandling-induced increases in particle levels, it is important to educate end-users about proper product handling. Furthermore, effective particle mitigation and reduction strategies should be developed for factor VIII, and other therapeutic protein products. Such efforts could lead to clinically useful approaches to reduce the levels of particles delivered to patients and to an associated reduction in adverse immunogenicity.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Ueda T,Nakamura K,Abe Y,Carpenter JFdoi
10.1016/j.xphs.2018.08.022subject
Has Abstractpub_date
2019-01-01 00:00:00pages
775-786issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(18)30523-9journal_volume
108pub_type
杂志文章abstract：:The biological activity of a series of 10 silver sulfanilamides is studied in relation to the physical parameters pK alpha, log K, and the aqueous solubility. None of the parameters demonstrate a simple relationship with the activity. A discussion of the significance of log K and the solubility in relation to the acti...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600730138
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abstract：:Griseofulvin/cyclodextrin interactions were investigated in aqueous environment and in solid state. Two cyclodextrin derivatives (beta-cyclodextrin and 2-hydroxypropyl beta-cyclodextrin) were used to prepare different physical mixtures and kneaded systems, and the drug/cyclodextrin ratios were 1:1 and 1:2 mol/mol. Sca...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970233x
更新日期：1998-07-01 00:00:00
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pub_type： 杂志文章,随机对照试验
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abstract：:The inhibitory effect of dioctyl sodium sulfosuccinate of hog pepsin activity was investigated over the pH 1.5-3.0 range. The inhibitory effect was studied using a natural substrate, hemoglobin, and a synthetic substrate, N-acetyl-L-phenylalanyl-L-diiodotyrosine. The mechanistic studies revealed that a substrate-inhib...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600650914
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abstract：:A column-switching high-performance liquid chromatographic assay combined with a heart-cutting technique and UV detection (LC/LC/UV) was developed to determine ceftibuten, a new oral cephalosporin, in human plasma. Plasma samples were directly injected into the first chromatographic column for sample cleanup and extra...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600810715
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doi：10.1016/j.xphs.2017.01.027
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600661113
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abstract：:First-order rate constants (k) were determined for the hydrolysis of ceftazidime in the pH range of 0.5 to 8.5 at 45, 55, and 65 degrees C by a stability-indicating HPLC assay. In the absence of buffer effects, the pH-rate expression was k = kH1f1(aH+) + kH2f2(aH+) + kH3f3(aH+) + kSf3 + kOHf3(aOH-), where KH and KOH a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840504
更新日期：1995-05-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600650308
更新日期：1976-03-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20403
更新日期：2005-08-01 00:00:00
abstract：:We report the preparation and structural characterization of a family of primary alcohol solvates of a small-molecule hydrochloride salt. The structures of the solvates are probed by powder and single crystal X-ray diffraction, and the compounds were additionally characterized by polarized light microscopy, thermograv...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2018.01.020
更新日期：2018-06-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1016/j.xphs.2018.01.018
更新日期：2018-06-01 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
pub_type： 杂志文章
doi：10.1021/js980006a
更新日期：1998-07-01 00:00:00
abstract：:In this article, we show that crystalline lactulose can be amorphized directly in the solid state by mechanical milling. Moreover, compared to similar materials, the amorphization kinetics of lactulose is found to be very rapid and the amorphous state thus obtained appears to be very stable against recrystallization o...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.09.013
更新日期：2019-02-01 00:00:00
abstract：:Aerosolized medicine is one of the fastest growing areas in the pharmaceutical industry. Dry powder aerosols of pharmaceutical compounds are particularly attractive for the prevention and treatment of respiratory diseases but are also emerging as a treatment option for systemic diseases. Engineering particles in dry p...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23168
更新日期：2012-09-01 00:00:00
abstract：:1-[4-(2-Cyclopropylmethoxyethyl)phenoxy]-3-[1-p-(bromoacetamidophe nyl) -2-methyl-2-propylamine]-2-propranol (8), which is a derivative of the beta 1-adrenergic agent betaxolol, was synthesized. Compound 8 showed less potent beta-adrenergic blocking activity than betaxolol in an in vitro test with guinea pig tracheal ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600741024
更新日期：1985-10-01 00:00:00
abstract：:While the number of clinical trials has continued to grow by about 20% in the past six months, no corresponding growth in product approval by the food and drug administration is seen or anticipated in the near future. Late-stage clinical failures due to lack of efficacy or toxicity continues to be a challenge. The opt...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21649
更新日期：2009-06-01 00:00:00
abstract：:Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility...
journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670426
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600730312
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doi：10.1002/jps.2600770508
更新日期：1988-05-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20513
更新日期：2006-02-01 00:00:00
abstract：:This study is to enhance the dissolution rate of a poorly water-soluble drug, quercetin, by fabricating nanocrystals using high-pressure homogenization. The particle size, crystallinity, dissolution, and antioxidant effects of fabricated quercetin nanocrystals have been investigated. Characterization of the original q...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.22446
更新日期：2011-06-01 00:00:00
abstract：:Avoiding unwanted immunogenicity is of key importance in the development of therapeutic drug proteins. Animal models are of less predictive value because most of the drug proteins are recognized as foreign proteins. However, different methods have been developed to obtain immunotolerant animal models. So far, the immu...
journal_title：Journal of pharmaceutical sciences
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更新日期：2013-03-01 00:00:00
abstract：:Thymopentin (Tp5) was loaded in poly-butylcyanoacrylate (PBCA) nanoparticles (NP) in order to enhance the oral bioavailability of Tp5. PBCA-Tp5-NP was prepared by nanoprecipitation methods. Dialyzing membrane method was employed to examine the in vitro release of PBCA-Tp5-NP in PBS, and Tp5 samples in the release medi...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.21148
更新日期：2008-06-01 00:00:00
abstract：:This work investigates the use of spray freeze-drying (SFD) to produce protein loaded particles suitable for epidermal delivery. In the first part of the study, the effects of formulation and process conditions on particle properties are examined. Aqueous solutions of trehalose produce SFD particles in the size range ...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.10204
更新日期：2002-10-01 00:00:00
abstract：:Progesterone release from monolithic devices prepared from various copolymers of poly(hydroxyethyl methacrylate) and poly(methoxyethoxyethyl methacrylate) or poly(methoxyethyl methacrylate) was examined. In general, plots of the fraction of drug released versus (time)1/2 were linear during the early stages of drug rel...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600700226
更新日期：1981-02-01 00:00:00
abstract：:The germacranolide sesquiterpene lactones costunolide, parthenolide, and costunolide diepoxide were isolated from the leaves of Magnolia grandiflora L. Costunolide diepoxide might be, at least in part, an artifact derived from air oxidation of parthenolide. The root bark yielded only costunolide together with the two ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670319
更新日期：1978-03-01 00:00:00
abstract：:Chlorthalidone was analyzed in the concentration range of 0.1-3.0 microgram/ml with a precision of +/- 0.05 microgram/ml. Chlorthalidone inhibition of the enzymatic hydrolysis rate of p-nitrophenyl acetate by bovine erythrocyte carbonic anhydrase was used as a basis for the determination. The amount of p-nitrophenol f...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661220
更新日期：1977-12-01 00:00:00
abstract：:The benzenesulfonate salt of an anti-methicillin-resistant Staphylococcus aureus carbapenem antibiotic studied is a crystalline, nonhygroscopic powder which is stable at room temperature, making it an ideal compound for long-term storage. However, the limited aqueous solubility of this salt prohibits parenteral admini...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.10084
更新日期：2002-04-01 00:00:00
