Abstract:
:Clinical lots of recombinant human platelet-activating factor acetylhydrolase (rhPAF-AH) were prepared in a lyophilized formulation. After reconstitution with sterile water for injection to form an aqueous solution (10 mM sodium citrate, 7.5 w/v% sucrose, and 0.1 w/v% Pluronic-F68, pH 6.5), a few visible, slowly growing particles formed consistently within hours at room temperature. To investigate the mechanism of this phenomenon, immediately after reconstitution, all protein aggregates and exogenous particles were removed by filtration. During 20 days incubation at room temperature, no visible aggregates formed in these filtered samples. In contrast, when nano-sized hydrophilic silica particles were added, they seeded rapid and extensive aggregation of rhPAF-AH. This effect was exacerbated in solutions containing a lower Pluronic-F68 concentration at 0.01%. Aggregation occurred even under conditions where rhPAF-AH adsorption was reversible, and induced no detectable changes to protein secondary and tertiary structures. Decreasing the extent (e.g., adding Pluronic-F68) or affinity (e.g., increasing solution pH) of rhPAF-AH adsorption on nano-sized silica particles was found to be effective at reducing aggregation. Accelerated aggregation was not observed when rhPAF-AH formulation was seeded with aggregated rhPAF-AH. These results show that rhPAF-AH aggregation proceeds through a heterogeneous nucleation-controlled mechanism, where exogenous particles present in solution serve as seeds on which rhPAF-AH adsorb, nucleate, and grow into large aggregates.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Chi EY,Weickmann J,Carpenter JF,Manning MC,Randolph TWdoi
10.1002/jps.20237subject
Has Abstractpub_date
2005-02-01 00:00:00pages
256-74issue
2eissn
0022-3549issn
1520-6017pii
S0022-3549(16)31697-5journal_volume
94pub_type
杂志文章abstract::Three dimensional terahertz pulsed imaging (TPI) was evaluated as a novel tool for the nondestructive characterization of different solid oral dosage forms. The time-domain reflection signal of coherent pulsed light in the far infrared was used to investigate film-coated tablets, sugar-coated tablets, multilayered con...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20789
更新日期:2007-02-01 00:00:00
abstract::The influence of ferric ions, EDTA, and visible light on the oxidation of methionine and the covalent reducible and nonreducible dimerization in human Insulin-like Growth Factor I (hIGF-I) in aqueous (1 mM) phosphate buffer solution were studied. A reduced factorial experiment with two levels of each factor was used. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js960484q
更新日期:1997-09-01 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 ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600791103
更新日期:1990-11-01 00:00:00
abstract::This study aims at investigating factors influencing humidity-induced recrystallization of amorphous lactose, produced by co-spray drying with particles of cellulose nanocrystals or sodium montmorillonite. In particular, the focus is on how the nanoparticle shape and surface properties influence the nanometer to micro...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.09.032
更新日期:2017-01-01 00:00:00
abstract::A procedure for the quantitative determination of adinazolam in plasma was developed. The drug, an N-demethylated metabolite, and an internal standard were extracted from basified plasma into ethyl acetate. After evaporation, the residue was dissolved in toluene which was washed with sodium hydroxide. The toluene was ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600730840
更新日期:1984-08-01 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
pub_type: 杂志文章
doi:10.1002/jps.10204
更新日期:2002-10-01 00:00:00
abstract::Controlled-release delivery of 6-beta-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeat...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22083
更新日期:2010-07-01 00:00:00
abstract::A α-helical GALA peptide (WEAALAEALAEALAEHLAEALAEALEALAA) has been found to possess dual functions: a pH-dependent inducer of endosomal escape, and a ligand that targets lung endothelium. In the present study, the flexibility of GALA was improved by modifying the edge with polyethylene glycol linker, to increase lung-...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.04.075
更新日期:2017-09-01 00:00:00
abstract::Three polymorphs (forms I-III), a monohydrate (form S2), and three new solvates [4:1 hydrate (form S1), monohydrate (form S3), and methanol half-solvate (form S4)] were isolated and characterized by X-ray powder diffractometry (XRPD), IR spectroscopy, differential scanning calorimetry (DSC), hot stage microscopy, solu...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600841007
更新日期:1995-10-01 00:00:00
abstract::The survival of Staphylococcus aureus was studied in 30 oral administration liquid medicaments (15 syrups and 15 solutions) to determine the effectiveness of the preservatives, the influence of the culture medium used in the enumeration of the surviving microorganisms, and the loss of the enzyme coagulase, phosphatase...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600820211
更新日期:1993-02-01 00:00:00
abstract::The disposition of radioactivity following oral administration of 14C-norgestimate was compared to that following administration of the drug in combination with 3H-ethinyl estradiol in humans. Seven normal, healthy female subjects were each administered one capsule orally containing 14C-norgestimate either alone (74.4...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600671020
更新日期:1978-10-01 00:00:00
abstract::Oral Almotriptan maleate (ALM) is used in the treatment of migraine; however, due to its extreme aqueous solubility, shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. Being flexible and lipophilic in nature, nanostructured lipid carriers (NLCs) represent a promising tool...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.04.007
更新日期:2020-07-01 00:00:00
abstract::Eight analogs of the fentanyl-type analgesics, in which the piperidine ring is restricted into a boat conformation, were evaluated for analgesic activity. All analogs were less active than fentanyl, but interesting conformational and structural relationships were observed. Results of the study are discussed. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600690934
更新日期:1980-09-01 00:00:00
abstract::A specific, sensitive, rapid, and reproducible analytical GLC method for lidocaine in human plasma, including pharmacokinetic parameters, is described. Aminopyrine is the internal standard. The method was used to study pharmacokinetics in four healthy volunteers following the administration of a lidocaine bolus at a d...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600661007
更新日期:1977-10-01 00:00:00
abstract::Sucrose is a common cryoprotectant and lyoprotectant to stabilize labile biopharmaceuticals during freeze-drying and storage. Sucrose-based formulations require low primary drying temperatures to avoid collapse and monoclonal antibody (mAb) containing products need to be stored refrigerated. The objective of this stud...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2019.10.016
更新日期:2020-01-01 00:00:00
abstract::Regional permeability coefficients of 19 drugs with different physicochemical properties were determined using excised segments from three regions of rat intestine: jejunum, ileum, and colon. The results are discussed in relation to the characteristics of the drug, i.e., MW (range 113-1071 Da), pKa, log D (octanol/wat...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js970218s
更新日期:1998-03-01 00:00:00
abstract::High-throughput lyophilization process was designed and developed for protein formulations using a single-step drying approach at a shelf temperature (Ts) of ≥40°C. Model proteins were evaluated at different protein concentrations in amorphous-only and amorphous-crystalline formulations. Single-step drying resulted in...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.11.021
更新日期:2019-04-01 00:00:00
abstract::Both nonequilibrium and equilibrium models were proposed to explain the optimal biological response to a set of congeners with respect to the oil-water partition coefficient (P). A detailed analysis of the kinetic model proposed by Hansch demonstrates the bilinear form of the model, with the initial slope of the logar...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600700110
更新日期:1981-01-01 00:00:00
abstract::The recently introduced four-parameter extended Hansen approach was used to study the solubility of p-hydroxybenzoic acid and methyl p-hydroxybenzoate in 32 and 35 individual solvents, respectively. The results are compared with those for benzoic acid in 40 solvents. Seventeen of the thirty-two or 53% of the calculate...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600730211
更新日期:1984-02-01 00:00:00
abstract::A round-robin study compared four methods of residual ethylene oxide analysis. Results from the six participating laboratories, along with a statistical treatment of the data, are presented. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600640837
更新日期:1975-08-01 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::Owing to proliferation of antibiotic-resistant bacteria, the use of antibiotics for livestock growth promotion is banned in many countries and alternatives to in-feed antibiotics are needed. Cinnamon essential oil exhibits strong in vitro antibacterial activity; however, direct addition of essential oils to animal fee...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2015.10.001
更新日期:2016-03-01 00:00:00
abstract::The effects of the granule size and density on the drying rate kinetics of tablet granulations were studied using lactose and sulfathiazole granules prepared with acacia mucilage and providone solution. The drying rate kinetics consisted of three distinct phases of drying when the drying rate was platted against remai...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600640631
更新日期:1975-06-01 00:00:00
abstract::The present work shows that the heated carbamazepine (CBZ) powder form III can be described as purely triclinic form I or a mixture of triclinic form I and monoclinic form III, depending on the resolution of the X-ray diffraction equipment used. Visual identification of the minor phase is possible when high-resolution...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22482
更新日期:2011-07-01 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...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.10.059
更新日期:2019-04-01 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::Transdermal delivery of fentanyl from various adhesive matrix formulations to achieve a steady-state skin flux was investigated. For this purpose, various pressure-sensitive adhesives selected from the three chemical classes of polymers (polyisobutylene (PIB), acrylate, and silicone adhesives) were characterized with ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js950415w
更新日期:1996-05-01 00:00:00
abstract::A sensitive, specific, high-performance liquid chromatographic procedure was developed for the measurement of plasma tiflamizole levels. Acidic plasma samples were extracted with three volumes of ether. The ether extracts were combined and evaporated to dryness. The residue was dissolved in acetonitrile, washed with h...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600731245
更新日期:1984-12-01 00:00:00
abstract::Canrenone can be determined by high-speed liquid chromatography in pharmaceutical dosage forms without interference from common excipients or degradation products. This stability-indicating assay, using o-nitroaniline as the internal standard, is rapid and accurate. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650135
更新日期:1976-01-01 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