Abstract:
PURPOSE:The aim was to evaluate fluorescent molecular rotors (DCVJ and CCVJ), which are mainly sensitive to viscosity, for the characterization of polysorbate-containing IgG formulations and compare them to the polarity-sensitive dyes ANS, Bis-ANS and Nile Red. METHODS:IgG formulations with polysorbate 20 or 80 were stressed below the aggregation temperature and analyzed by steady-state and time-resolved fluorescence and by HP-SEC with UV and fluorescent dye detection (Bis-ANS and CCVJ). Furthermore, commercial protein preparations of therapeutic proteins (Enbrel 50 mg, Humira 40 mg and MabThera 100 mg) were aggregated accordingly and analyzed with CCVJ fluorescence and HP-SEC. RESULTS:Contrarily to (Bis-)ANS and Nile Red, the molecular rotors DCVJ and CCVJ showed low background fluorescence in polysorbate-containing buffers. Time-resolved fluorescence experiments confirmed the steady-state fluorescence data. Both DCVJ and CCVJ showed enhanced fluorescence intensity for aggregated IgG formulations and were suitable for the characterization of polysorbate-containing IgG formulations in steady-state fluorescence and HP-SEC with dye detection (CCVJ). CCVJ was capable of detecting thermally induced aggregation in the commercial polysorbate-containing products Enbrel 50 mg, Humira 40 mg and MabThera 100 mg. CONCLUSION:Fluorescent molecular rotors are suitable probes to detect aggregation in polysorbate-containing IgG formulations.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Hawe A,Filipe V,Jiskoot Wdoi
10.1007/s11095-009-0020-2subject
Has Abstractpub_date
2010-02-01 00:00:00pages
314-26issue
2eissn
0724-8741issn
1573-904Xjournal_volume
27pub_type
杂志文章abstract:PURPOSE:A mechanism-based PK-PD model was developed to predict the time course of dopamine D(2) receptor occupancy (D(2)RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. METHODS:A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0477-7
更新日期:2011-10-01 00:00:00
abstract:PURPOSE:The aim was to replace the traditional 21-day Caco-2 permeability protocol by a more high-throughput assay. METHODS:Caco-2 cells were seeded at high density in 96-well plates in novel cell culture boxes. After 7 days, drug permeability studies were performed. Samples were analyzed by a new UV detection method....
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000008043.71001.43
更新日期:2003-12-01 00:00:00
abstract:PURPOSE:This study compared gene expression profiles in mouse lungs after administration of the cationic polymers polyethyleneimine (PEI) or chitosan alone or formulated with a luciferase reporter plasmid (PEI-pLuc, chitosan-pLuc). METHODS:The polymers and formulations were administered intratracheally to Balb/c mice ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9563-7
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:Solid dispersions (SDs) represent the most common formulation technique used to increase the dissolution rate of a drug. In this work, the three most common methods used to prepare SDs, namely spray-drying, solvent-casting and freeze-drying, have been compared in order to investigate their effect on increasing ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-2778-1
更新日期:2020-02-19 00:00:00
abstract::The delivery of therapeutic nucleic acids to neurons has the potential to treat neurological disease and spinal cord injury. While select viral vectors have shown promise as gene carriers to neurons, their potential as therapeutic agents is limited by their toxicity and immunogenicity, their broad tropism, and the cos...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-007-9439-5
更新日期:2008-05-01 00:00:00
abstract::Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018904825958
更新日期:1993-03-01 00:00:00
abstract:PURPOSE:To assess the role of intestinal CYP2D6 in oral first-pass drug clearance by comparing the enzyme content and catalytic activity of a prototype CYP2D6 substrate, metoprolol, between microsomes prepared from human intestinal mucosa and from human livers. METHODS:Microsomes were prepared from a panel of 31 human...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018989211864
更新日期:1999-08-01 00:00:00
abstract::The transient dynamic swelling and dissolution behavior during the release of a growth hormone releasing peptide, [D-Trp2-D-Phe5]GHRP, from erodible, non-cross-linked poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been investigated at pH 7.4 as a function of buffer concentration. Although the swell...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018902404036
更新日期:1993-07-01 00:00:00
abstract::Significant efforts are made to characterize molecular liabilities and degradation of the drug substance (DS) and drug product (DP) during various product life-cycle stages. The in vivo fate of a therapeutic protein is usually only considered in terms of pharmacokinetics (PKs) and pharmacodynamics (PDs). However, the ...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-019-2689-1
更新日期:2020-01-03 00:00:00
abstract:PURPOSE:Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-s...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02901-0
更新日期:2020-08-13 00:00:00
abstract:PURPOSE:To dynamically analyze the processes of oral absorption and hepatobiliary distribution of telmisartan using positron emission tomography (PET). METHODS:(11)C-labeled telmisartan ([(11)C]TEL) was orally administered to rats with or without non-radiolabeled telmisartan (0.5, and 10 mg/kg). PET scanning of abdomi...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0768-7
更新日期:2012-09-01 00:00:00
abstract:PURPOSE:To examine the transport characteristics of the multidrug resistance-associated protein (MRP) substrate fluorescein across the isolated rat small intestinal segments. METHODS:The transport of fluorescein was studied in side-by-side diffusion chambers under short-circuited conditions at physiological pH. RESUL...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000022410.89709.c3
更新日期:2004-04-01 00:00:00
abstract:OBJECTIVE:Amorphous pharmaceuticals, a viable approach to enhancing bioavailability, must be stable against crystallization. An amorphous drug can be stabilized by dispersing it in a polymer matrix. To implement this approach, it is desirable to know the drug's solubility in the chosen polymer, which defines the maxima...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9784-z
更新日期:2009-04-01 00:00:00
abstract::Many drugs and desirable phytochemicals are bitter, and bitter tastes are aversive. Food and pharmaceutical manufacturers share a common need for bitterness-masking strategies that allow them to deliver useful quantities of the active compounds in an acceptable form and in this review we compare and contrast the chall...
journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-014-1480-6
更新日期:2014-11-01 00:00:00
abstract::Primaquine (I), a 6-methoxy-8-aminoqumoline derivative used for the treatment of malaria has previously been shown to be metabolized to 8-(3-carboxy-l-methyl-propylamino)-6-methoxyquinoline by both micro-organisms and laboratory rats. Reported herein is the synthesis of this novel metabolite. ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016311616719
更新日期:1984-03-01 00:00:00
abstract::The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absor...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016251023427
更新日期:1995-01-01 00:00:00
abstract::The fluxes of nitroglycerine (NG) through human abdominal epidermis from different individuals were measured in vitro at 32°C. The mean NG flux for the entire group was 16.9 µg/cm(2) × hr, with a standard deviation of 47.7%. There are no significant differences in the means and the variances of NG fluxes between males...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016381017357
更新日期:1986-02-01 00:00:00
abstract:PURPOSE:To develop an efficient tumor vasculature-targeted polymeric micelle delivery system for combretastatin A4 (CA4), a novel antivascular agent. METHODS:CA4-loaded micelles were prepared from poly (ethylene glycol)-b-poly (d, l-lactide) copolymers. RGD peptides that target integrins alphavbeta3 and alphavbeta5, m...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0184-9
更新日期:2010-09-01 00:00:00
abstract::Moexipril [2-[(1-ethoxycarbonyl)-3-phenylpropyl]amino-1-oxopropyl]-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (S,S,S)], an ester prodrug of an ACE inhibitor, was formulated in controlled-release preparations with a range of in vitro release rates, to provide a prolonged input of drug in vivo. Howe...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015919413103
更新日期:1989-09-01 00:00:00
abstract:PURPOSE:This study aimed to characterize the transepithelial transport of miltefosine (HePC), the first orally effective drug against visceral leishmaniasis, across the intestinal barrier to further understand its oral absorption mechanism. MATERIALS AND METHODS:Caco-2 cell monolayers were used as an in vitro model of...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9170-7
更新日期:2007-03-01 00:00:00
abstract:PURPOSE:To investigate cellular uptake pathways of novel anionic siRNA-lipoplexes as a function of formulation composition. METHODS:Anionic formulations with anionic lipid/Ca(2+)/siRNA ratio of 1.3/2.5/1 (AF1) and 1.3/0.3/1 (AF2) were utilized. Uptake mechanisms were investigated using uptake inhibition and co-localiz...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0952-9
更新日期:2013-04-01 00:00:00
abstract::The effect of freezing on formation of soluble and insoluble aggregates of human growth hormone (hGH) was studied. The amount of soluble aggregates was affected very little by freezing regardless of the cooling rate. In contrast, the formation of insoluble aggregates (particulates), as determined by light scattering i...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015888704365
更新日期:1991-11-01 00:00:00
abstract:PURPOSE:To better understand the nature of drug-excipient interactions we have studied the phase behavior of amorphous binary and ternary mixtures of citric acid, indomethacin and PVP, as model systems. METHODS:We have prepared amorphous mixtures by co-melting or coprecipitation from solvents, and have measured glass ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011983606606
更新日期:1998-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018875130152
更新日期:1999-04-01 00:00:00
abstract::A new transdermal therapeutic system (TTS) for nitroglycerin is presented that controls release of the active substance by means of desorption and diffusion. The drug release, in the dosage range examined under sink conditions, is independent of electrolytes and pH of the aqueous acceptor medium, but it does depend on...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016361921803
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:We compared cationic, polyamine-coated microparticles (MPs) and anionic, protein-coated MPs with respect to their phagocytosis and phagosomal fate in dendritic cells (DCs) and macrophages (Mphi). METHODS:Polystyrene MPs were surface modified by covalent coupling with fluorescein isothiocyanate-labeled polyamin...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1022271020390
更新日期:2003-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-013-1060-1
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:Cannabinoids have been associated with tumor regression and apoptosis of cancer cells. Recently, we have shown that R(+)-methanandamide (R(+)-MA) induces apoptosis of H4 human neuroglioma cells via a mechanism involving de novo expression of the cyclooxygenase-2 (COX-2) enzyme. The present study investigated a ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-8815-2
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:To identify materials and processes which effect supersaturation of the GI milieu for low solubility drugs in order to increase oral bioavailability. METHODS:A variety of small and polymeric molecules were screened for their ability to inhibit drug precipitation in supersaturated solutions. The best polymeric ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-9852-z
更新日期:2009-06-01 00:00:00
abstract:PURPOSE:A major challenge facing nanoparticle-based delivery of chemotherapy agents is the natural and unavoidable accumulation of these particles in healthy tissue resulting in local toxicity and dose-limiting side effects. To address this issue, we have designed and characterized a new prodrug nanoparticle with contr...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2205-4
更新日期:2017-10-01 00:00:00