Abstract:
:This study explored the ability to conduct primary drying during lyophilization at product temperatures above the glass transition temperature of the maximally freeze-concentrated solution (Tg′) in amorphous formulations for four proteins from three different classes. Drying above Tg′ resulted in significant reductions in lyophilization cycle time. At higher protein concentrations, formulations freeze dried above Tg′ but below the collapse temperature yielded pharmaceutically acceptable cakes. However, using an immunoglobulin G type 4 monoclonal antibody as an example, we found that as protein concentration decreased, minor extents of collapse were observed in formulations dried at higher temperatures. No other impacts to product quality, physical stability, or chemical stability were observed in this study among the different drying conditions for the different proteins. Drying amorphous formulations above Tg′, particularly high protein concentration formulations, is a viable means to achieve significant time and cost savings in freeze-drying processes.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Depaz RA,Pansare S,Patel SMdoi
10.1002/jps.24705subject
Has Abstractpub_date
2016-01-01 00:00:00pages
40-9issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(15)00169-0journal_volume
105pub_type
杂志文章abstract::We investigate the presence of a surface species for the active pharmaceutical ingredient (API) AZD9496 with dynamic nuclear polarization surface enhanced nuclear spectroscopy (DNP SENS). We show that using DNP we can elucidate the presence of an amorphous form of the API at the surface of crystalline particles of the...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.12.037
更新日期:2021-01-05 00:00:00
abstract::A rotating-basket apparatus for dissolution testing of veterinary bolus tablets was designed and constructed. Sulfamethazine boluses containing different disintegrating agents were evaluated in vitro and by blood level data following administration to cattle. The dissolution t50 and various pharmacokinetic parameters ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600651231
更新日期:1976-12-01 00:00:00
abstract::The objectives of this study were (i) to characterize the plasmid DNA encoding the chloramphenicol acetyltransferase reporter gene (pCAT) complexed with cationic liposomes (Lipofectin and LipofectACE) in terms of particle size and zeta potential, (ii) to compare pharmacokinetic characteristics, and (iii) to study the ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600841102
更新日期:1995-11-01 00:00:00
abstract::Corneal permeability data taken from the literature were analyzed for possible quantitative relationships with physicochemical properties. Although a parabolic relationship was obtained with good correlation between lipophilicity, as expressed by the 1-octanol-water partition coefficients, log Poctanol (or the distrib...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js960076m
更新日期:1996-08-01 00:00:00
abstract::This study describes the adaptation of conventional titrimetric and spectrophotometric techniques to a microscale for the determination of drug ionization constants (pKa) and partition coefficients (log P). The apparatus for determining pKa and compound purity (or equivalent weight) consists of a three-port conical gl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js970057s
更新日期:1998-02-01 00:00:00
abstract::Caco-2 cell monolayers are widely used systems for predicting human intestinal absorption. This study was carried out to develop a quantitative structure-property relationship (QSPR) model of Caco-2 permeability using a novel genetic algorithm-based partial least squares (GA-PLS) method. The Caco-2 permeability data f...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10214
更新日期:2002-10-01 00:00:00
abstract::The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24137
更新日期:2014-11-01 00:00:00
abstract::A tetrazole ring is often used in drug discovery as a replacement for the carboxylic acid group. Previous work indicates that compounds containing a tetrazole moiety show asymmetric permeability in Caco-2 cells characteristic of an efflux transporter substrate. The aim of this study is to determine which transporters ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20526
更新日期:2006-04-01 00:00:00
abstract::Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised lysosomal levels of cystine in the cells of all the organs. It is treated by the 6-h oral administration of the aminothiol, cysteamine, which has an offensive taste and smell. In an attempt to reduce this frequency and improve the tr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23246
更新日期:2012-10-01 00:00:00
abstract::Pinacidil [(+/-)-2-cyano-1-(4-pyridyl)-3-(1,2,2-trimethylpropyl)guanidine monohydrate] is a novel, direct-acting vasodilator antihypertensive agent. The cyano 14C-labeled drug is rapidly and completely absorbed after an oral 12.5-mg dose in solution. The blood:plasma concentration ratios (0.8-0.9) indicate transient p...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600770212
更新日期:1988-02-01 00:00:00
abstract::Modifications of antibacterial activity have been demonstrated using combinations of two antibacterials from trimethoprim, sulfonamides (sulfadiazine, sulfamerazine, and silver sulfadiazine), silver nitrate, and dibromopropamidine isethionate, either formulated in a cream base or dissolved in peptone water. The creams...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800912
更新日期:1991-09-01 00:00:00
abstract::Glycerol stabilizes cyanocob(III)alamin (vitamin B12) against anaerobic photolysis by a high-intensity UV light source or a low-intensity fluorescent light source. The likely mechanism for stabilization by viscosigens is a decrease in diffusion and an enhancement of radical-pair recombination. Glycerol (25% or greater...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600820619
更新日期:1993-06-01 00:00:00
abstract::Poor water solubility leads to low dissolution rate and consequently, it can limit bioavailability. Solid dispersions, where the drug is dispersed into an inert, hydrophilic polymer matrix can enhance drug dissolution. Solid dispersions were prepared using phenacetin and phenylbutazone as model drugs with polyethylene...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22613
更新日期:2011-10-01 00:00:00
abstract::The ICH Q1B guidance and additional clarifying manuscripts provide the essential information needed to conduct photostability testing for pharmaceutical drug products in the context of manufacturing, packaging, and storage. As the previous 2 papers in this series highlight for drug products administered by injection (...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1016/j.xphs.2016.02.035
更新日期:2016-05-01 00:00:00
abstract::Solution preparation is the first unit operation of the manufacturing process for spray-dried solid dispersions. Visual inspection and offline high-performance liquid chromatography analysis are routinely used to assess the solution preparation end point as well as the final solution composition. However, the accuracy...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.10.022
更新日期:2019-03-01 00:00:00
abstract::Glasses were prepared from a number of barbiturates. The viscosities and glass transition temperatures of the glasses were dependent on the structure of the groups present on the C-5 and N-1 atoms. Solid dispersions were prepared from three selected barbiturates formulated with citric acid. The glass transition temper...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600671126
更新日期:1978-11-01 00:00:00
abstract::The hydrophobic substituent parameter for a system of meta- and para-disubstituted benzenes, XC6H4Y, defined as pi X/PhY = log PXC6H4Y - log PC6H5Y, where P is the octanol-water partition coefficient and X and Y are variable and fixed substituents, respectively, varies from one system to another, according to the vari...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600720319
更新日期:1983-03-01 00:00:00
abstract::With the introduction of Quality by Design (QbD) to the pharmaceutical industry, there has been an increased focus on understanding the nature of particles and composites, with the aim of understanding and modeling how they interact in complex systems, leading to robust dosage forms. Particle characterization tools ha...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.24382
更新日期:2015-05-01 00:00:00
abstract::Solid dispersion (SD) of indomethacin with crospovidone (CrosPVP) shows useful characteristics for preparation of dosage forms. This study aimed to determine the types of drugs that could adopt a stable amorphous form in SD. Twenty compounds with various melting points (70-218 degrees C), molecular weights (135-504) a...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20794
更新日期:2007-06-01 00:00:00
abstract::The metabolic fate of aprophen hydrochloride (2-diethylaminoethyl 2,2-diphenylpropionate) was studied in rats after intravenous administration. Both 14C-labeled and unlabeled aprophen were used in these studies. Blood samples were collected and analyzed to determine the identities of the metabolites formed. Utilizing ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600770210
更新日期:1988-02-01 00:00:00
abstract::Regular insulin, NPH insulin, glargine insulin, calcitonin, and human growth hormone were administered to rats nasally with 0.125% tetradecyl-beta-D-maltoside (TDM), or at various times after TDM treatment. Absorption of all five peptides was enhanced initially and diminished in a time-dependent manner as the interval...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21977
更新日期:2010-04-01 00:00:00
abstract::The solubility of a series of compounds was determined in a wide polarity spectrum of normal aliphatic alcohols over a limited temperature range. The solutes chosen were the methyl through n-butyl p-hydroxybenzoates, several of these being useful preservatives. Solubility profiles were determined for these compounds, ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600660110
更新日期:1977-01-01 00:00:00
abstract::An equation was developed which enables blood level data to be utilized for determining whether or not the first-order absorption and elimination rate constants are equal in the one-compartment open model. This equation was tested using simulated data with excellent results. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740521
更新日期:1985-05-01 00:00:00
abstract::A simple and sensitive assay for quantitating 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (1; BMY 26517) in human plasma was developed using high-performance liquid chromatography with fluorescence detection. The method involves precipitation of protein and reversed-phase chromatography. The method i...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600761216
更新日期:1987-12-01 00:00:00
abstract::Antibody therapeutics with poor solubility in the subcutaneous matrix may carry unintended risks when administered to patients. The objective of this work was to estimate the risk of antibodies that precipitate in vitro at neutral pH by determining the impact of poor solubility on distribution of the drug from the inj...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2019.01.015
更新日期:2019-06-01 00:00:00
abstract::This article describes a procedure to facilitate scale-up for the primary drying phase of lyophilization using a combination of empirical testing and numerical modeling. Freeze dry microscopy is used to determine the temperature at which lyophile collapse occurs. A laboratory scale freeze-dryer equipped with manometri...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21430
更新日期:2009-01-01 00:00:00
abstract::Recently, our laboratory reported that intravenous immunoglobulin (IVIG) treatment increased antiplatelet antibody (7E3) clearance in a rat model of immune thrombocytopenic purpura (ITP). However, due to the multifaceted nature of IVIG therapy, the contribution of this increase in antiplatelet antibody clearance to th...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10364
更新日期:2003-06-01 00:00:00
abstract::New butyrate derivatives were synthesized to investigate the residence time of potent butyric acid in vivo. These derivatives were triglycerides in which one, two, or three butyric acid molecules were bound to glycerol or to mono- and dipalmitic esters of glycerol. Pharmacokinetic studies showed that a constant plasma...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::An HPLC method for determining total pyridoxal from plasma was developed for a relative bioavailability comparison of two oral vitamin B6 (pyridoxine HCl) preparations. After cleavage of the pyridoxal-5-phosphate with the acid phosphatase enzyme, the total pyridoxal was determined by HPLC. Pyridoxal was separated on a...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600820921
更新日期:1993-09-01 00:00:00
abstract::A GLC-mass spectrometric assay for methylphenidate in biological fluids was developed using the ethyl ester homolog of the drug as the internal standard. The procedure has a lower level of sensitivity of 1.2 ng/ml and is based on GLC-mass spectrometic monitoring of the m/e 180 ion common to the mass spectra of the N-t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600660633
更新日期:1977-06-01 00:00:00