Abstract：
:We studied the effects of pH and solution additives on freezing-induced perturbations in the tertiary structure of a monoclonal antibody (mAb) by intrinsic tryptophan fluorescence spectroscopy. In general, freezing caused perturbations in the tertiary structure of the mAb, which were reversible or irreversible depending on the pH or excipients present in the formulation. Protein aggregation occurred in freeze-thawed samples in which perturbations of the tertiary structure were observed, but the levels of protein aggregates formed were not proportional to the degree of structural perturbation. Protein aggregation also occurred in freeze-thawed samples without obvious structural perturbations, most likely because of freeze concentration of protein and salts, and thus reduced protein colloidal stability. Therefore, freezing-induced protein aggregation may or may not first involve the perturbation of its native structure, followed by the assembly processes to form aggregates. Depending on the solution conditions, either step can be rate limiting. Finally, this study demonstrates the potential of fluorescence spectroscopy as a valuable tool for screening therapeutic protein formulations subjected to freeze-thaw stress.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Liu L,Braun LJ,Wang W,Randolph TW,Carpenter JFdoi
10.1002/jps.24013subject
Has Abstractpub_date
2014-07-01 00:00:00pages
1979-1986issue
7eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30519-0journal_volume
103pub_type
杂志文章abstract：:Quality-by-design (QbD) is a systematic approach to drug development, which begins with predefined objectives, and uses science and risk management approaches to gain product and process understanding and ultimately process control. The concept of QbD can be extended to analytical methods. QbD mandates the definition ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.22325
更新日期：2011-03-01 00:00:00
abstract：:Stable protein nanostructured particles, produced by spray freezing into liquid (SFL) nitrogen, were encapsulated uniformly into microspheres to reduce the burst release over the first 24 h. The denaturation and aggregation of these bovine serum albumin (BSA) high-surface area particles were minimal due to ultra-rapid...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20209
更新日期：2005-01-01 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
pub_type： 杂志文章
doi：10.1002/jps.23447
更新日期：2013-03-01 00:00:00
abstract：:Cyclosporin A (CyA) interacts with lipid membranes. Binding reaction and membrane location of CyA and analogs were examined with 2H-NMR, high-sensitivity isothermal titration calorimetry (ITC), and CD spectroscopy. Effects of CyA and charged analogs on the phosphocholine head group and on the membrane interior were in...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10071
更新日期：2002-03-01 00:00:00
abstract：:The standard free energy change (delta G0) for equilibrium dissolution in binary solvent mixtures is written as a sum of effects arising from solvent-solvent interactions (the general medium effect), solvent-solute interactions (the solvation effect), and solute-solute interactions (the intersolute effect). The genera...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810418
更新日期：1992-04-01 00:00:00
abstract：:A method was developed for the baseline separation of common free bile acids by supercritical fluid chromatography. A phenylbonded silica column, with UV detection at 210 nm, and carbon dioxide modified with methanol as the mobile phase were used. The influence of the stationary phase, modifier concentration, temperat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820110
更新日期：1993-01-01 00:00:00
abstract：:A few 1,2-bis(N-alkylaminomethyl)indolizines, simple indolizinecarboxylic acids, and several 6-alkoxyindolizine-2-carboxylic acids were synthesized and screened as possible oral hypoglycemic agents. The absence of any significant hypoglycemic activity excludes these compounds from the predicted structural lead provide...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：
更新日期：1975-02-01 00:00:00
abstract：:A simulation study was done to determine if 72 h is the most informative sampling duration for bioequivalence (BE) determination in parallel-designed BE studies with drugs that have half-lives of at least 30 h. The impact of absorption and elimination half-lives on informative sampling was evaluated. Two-treatment par...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23296
更新日期：2012-11-01 00:00:00
abstract：:The concept of cosolvent exclusion was developed by a group of Timasheff's laboratory in 1970-1990 and is currently used widely to explain the effects of a variety of cosolvents on the stability and solubility of macromolecules. Not surprisingly, these concepts have had substantial influence in the fields of formulati...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2018.05.006
更新日期：2018-09-01 00:00:00
abstract：:Conventionally, it is believed that the fraction of orally administered drugs absorbed from the intestine (Fa) and intestinal availability (Fg) are independently determined by the apical membrane permeation and intestinal metabolism, respectively. However, the validity of this belief has not been well discussed, and F...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2015.11.005
更新日期：2016-02-01 00:00:00
abstract：:The purpose of this study was to evaluate the cardiovascular effects of two potential beta-hydroxylase inhibitors, a dithiocarbamate and a thiourea derivative of d-amphetamine, 1 and 2, respectively. These compounds when given intravenously elicited a significant dose-dependent depressor effect in normotensive rats an...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740621
更新日期：1985-06-01 00:00:00
abstract：:The development of an ocular dosage form containing xanthan gum and capable of interacting with mucin in the precorneal area is a challenge. The polymer concentration that can be applied is restricted because of the limited patient acceptability of highly viscous preparations. The precorneal mucin concentration is low...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10106
更新日期：2002-04-01 00:00:00
abstract：:The concentrations of antipyrine in plasma and saliva were equivalent in normal volunteers and in patients with acute viral hepatitis following oral doses of antipyrine. Estimates of clearance, volume of distribution, and half-life made from either plasma or saliva samples were not statistically different in these sub...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660140
更新日期：1977-01-01 00:00:00
abstract：:The particle sizing performance of a Next Generation Pharmaceutical Impactor (NGI) was compared to that of an Andersen cascade impactor (ACI). A single lot of Vanceril MDIs containing beclomethasone dipropionate (BDP) was used throughout. MDIs were sampled into NGI and ACI in accordance with USP recommendations, at 30...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20091
更新日期：2004-07-01 00:00:00
abstract：:Complex dosing regimens simulated in the literature using a universal dosing regimen were calculated with a general dosing program developed using the program CONSAM. The program provides a rapid method of calculating nonuniform dosing regimens for up to n = 3 compartments for any linear model. Subject data can also b...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600800406
更新日期：1991-04-01 00:00:00
abstract：:A stereoselective and sensitive method for the determination of nilvadipine, a new dihydropyridine calcium antagonist, in human plasma was developed. An internal standard, the deuterated analogue of racemic nilvadipine, was added to the plasma and extracted with an n-hexane:ethyl acetate (92.5:7.5) mixture under alkal...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760410
更新日期：1987-04-01 00:00:00
abstract：:This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for developing continuous proc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24252
更新日期：2015-03-01 00:00:00
abstract：:The aim of the study was to determine and compare the degree of swelling and the swelling kinetics of poly(ethylene oxide) (PEO) hydrophilic matrix tablets without any additives for matrixes with different molecular weight polydispersities. A wide range of "mixed" polydisperse PEO tablets were obtained by mixing two P...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21892
更新日期：2010-03-01 00:00:00
abstract：:A GLC method is described for the determination of iminodibenzyl and desipramine impurities in imipramine hydrochloride and its formulated products. These impurities were extracted from an alkaline solution with a mixture of 30% methylene chloride in hexane for chromatography on a 3% OV-17 GLC column. Iminodibenzyl wa...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710515
更新日期：1982-05-01 00:00:00
abstract：:The progress in continuous downstream manufacturing of oral solid doses demands effective real-time process management, with monitoring at its core. This study evaluates the feasibility of using a commercial sensor to measure the mass flow rate of the particulates, a critical process variable in continuous manufacturi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.08.019
更新日期：2017-12-01 00:00:00
abstract：:The objective of the current study was to evaluate the performance of Raman and near-infrared (NIR) techniques combined with chemometrics in characterizing the critical quality attributes of brompheniramine (BP)-tannate complexes. Seven complexes were prepared and evaluated for chemical interactions, solubilities, dis...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23030
更新日期：2012-04-01 00:00:00
abstract：:Isothermal crystallization of amorphous nifedipine, phenobarbital, and flopropione was studied at temperatures above and below their glass transition temperatures (T(g)). A sharp decrease in the crystallization rate with decreasing temperature was observed for phenobarbital and flopropione, such that no crystallizatio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/(SICI)1520-6017(200003)89:3<408::AID-JPS11
更新日期：2000-03-01 00:00:00
abstract：:Nonionic block copolymers are surfactants synthesized using propylene oxide and ethylene oxide, and they can be designed so that individual copolymers have unique vaccine adjuvant properties. We have designed and produced nonionic block copolymers based on high molecular weight (MW), 9-15 kDA, cores of poly(oxypropyle...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980072c
更新日期：1998-11-01 00:00:00
abstract：:A theoretical analysis of a proposed drug delivery device is presented. The device is of cylindrical shape with an opening on its side surface. Analytical expressions for the temporal variations in the amount of drug released and the size of the unreleased portion of the device are derived. The result of numerical sim...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810905
更新日期：1992-09-01 00:00:00
abstract：:We investigated the effects of excipients in solutions of keratinocyte growth factor 2 (KGF-2) on protein aggregation during agitation as well as on interfacial shear rheology at the air-water interface. Samples were incubated with or without agitation, and in the presence or absence of the excipients heparin, sucrose...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23622
更新日期：2013-08-01 00:00:00
abstract：:Fibril formation (aggregation) of human and bovine insulin and six human insulin mutants in hydrochloric acid were investigated by visual inspection, Thioflavin T fluorescence spectroscopy, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. The fibrillation tendencies of the wi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10238
更新日期：2002-12-01 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：:This article shows how milling can be used to explore the phase diagram of pharmaceuticals. This process has been applied to sulindac. A short milling has been found to trigger a polymorphic transformation between form II and form I upon heating which is not seen in the nonmilled material. This possibility was clearly...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.03.017
更新日期：2019-08-01 00:00:00
abstract：:The aim of this study was to develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of a bicyclolide, modithromycin, to explain its concentration-dependent bactericidal activity based on the drug-bacterium interaction model that we developed. We have already reported the applicability of model to the time-dependent...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23897
更新日期：2014-04-01 00:00:00
abstract：:The significance of factors such as drug solubility, polymer molecular weight, drug loading dose, compression force, and hydrodynamic conditions on drug release from a swellable hydrophilic delivery system was investigated. Hydroxypropyl methylcellulose (HPMC) and pectin were major polymeric constituents of the delive...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js960307p
更新日期：1997-03-01 00:00:00
