Abstract：
:Successful development of stable solid protein formulations usually requires the addition of one or several excipients to achieve optimal stability. In these products, there is a potential risk of an inhomogeneous distribution of the various ingredients, specifically the ratio of protein and stabilizer may vary. Such inhomogeneity can be detrimental for stability but is mostly neglected in literature. In the past, it was challenging to analyze inhomogeneous component distribution, but recent advances in analytical techniques have revealed new options to investigate this phenomenon. This paper aims to review fundamental aspects of the inhomogeneous distribution of components of freeze-dried and spray-dried protein formulations. Four key topics will be presented and discussed, including the sources of component inhomogeneity, its consequences on protein stability, the analytical methods to reveal component inhomogeneity, and possible solutions to prevent or mitigate inhomogeneity.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Nguyen KTT,Frijlink HW,Hinrichs WLJdoi
10.1016/j.xphs.2019.10.010subject
Has Abstractpub_date
2020-01-01 00:00:00pages
134-153issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(19)30645-8journal_volume
109pub_type
杂志文章,评审abstract：:A sucrose-lactose-starch granulation was used to study particulate motion and attrition in a fluid bed dryer. There is some classification of material in the dryer as drying proceeds; fine particles are dried faster and become less dense, and the less dry but denser large particles show some (although not great) accum...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600641127
更新日期：1975-11-01 00:00:00
abstract：:The influence of hepatic uptake and efflux, which includes passive diffusion and transporter-mediated component, on drug distribution volumes [steady-state volume of distribution (V(ss)) and terminal volume of distribution (V(β))], mean residence time (MRT), clearance, and terminal half-life is considered using a simp...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22696
更新日期：2011-11-01 00:00:00
abstract：:Membrane permeation enhancers have received significant attention in recent years for enabling the oral absorption of poorly permeable drug molecules. In this study, we investigated the ability of His-Ala-Val (HAV) and Ala-Asp-Thr (ADT) peptides derived from the extracellular-1 (EC1) domain of E-cadherin proteins to i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.12.018
更新日期：2020-12-23 00:00:00
abstract：:A simple, sensitive GLC assay was developed for fusaric acid, the active metabolite of bupicomide, to follow the disposition of this investigational antihypertensive agent in patients undergoing therapy. Fusaric acid is efficiently extracted from biological samples, derivatized by on-column methylation, and chromatogr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650430
更新日期：1976-04-01 00:00:00
abstract：:Drying is a common pharmaceutical process, whose potential to modify the final drug and/or dosage form properties is often underestimated. In the present study, pellets consisting of the matrix former calcium stearate (CaSt) incorporating the active pharmaceutical ingredient ibuprofen were prepared via wet extrusion a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23707
更新日期：2013-11-01 00:00:00
abstract：:A characterization and optimization of the in vitro transdermal iontophoretic transport of 5-hydroxy-2-(N,N,-di-n-propylamino)tetralin (5-OH-DPAT) is presented. The utility of acetaminophen as a marker of electroosmotic flow was studied as well. The following parameters of iontophoretic transport of 5-OH-DPAT were exa...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21833
更新日期：2010-01-01 00:00:00
abstract：:Boron analogues of carbamoylcholine and thiocholine and esters of these analogues were prepared. These compounds were fairly stable toward hydrolysis and demonstrated moderate anti-inflammatory and hypolipidemic activities in mice. The hypolipidemic activity of the compounds at a dose of 8 mg/kg/day was equivalent in ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810514
更新日期：1992-05-01 00:00:00
abstract：:Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying in a larger scale. In this st...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.09.027
更新日期：2017-01-01 00:00:00
abstract：:4,5-Dimethoxykynuramine was synthesized in a three-step sequence originating with veratrole. Indirect evidence indicates that the drug was converted in vivo to the hypotensive agent 6,7-dimethoxy-4-quinolinol by the action of monoamine oxidase. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670344
更新日期：1978-03-01 00:00:00
abstract：:SARS-CoV-2 utilizes the IMPα/β1 heterodimer to enter host cell nuclei after gaining cellular access through the ACE2 receptor. Ivermectin has shown antiviral activity by inhibiting the formation of the importin-α (IMPα) and IMPβ1 subunits as well as dissociating the IMPα/β1 heterodimer and has in vitro efficacy agains...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.08.024
更新日期：2020-12-01 00:00:00
abstract：:Accurate prediction of target occupancy facilitates central nervous system drug development. In this review, we discuss the predictability of serotonin transporter (SERT) occupancy in human brain estimated from in vitro Ki values for human SERT and plasma concentrations of unbound drug (Cu,plasma), as well as the impa...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2017.05.007
更新日期：2017-09-01 00:00:00
abstract：:Detection and quantification of the amorphous phase of etoricoxib bulk drug substances, a selective cycloogenase-2 inhibitor used for the treatment of osteoarthritis, rheumatoid arthritis, and dental pain, was carried out using modulated differential scanning calorimetry (MDSC), dynamic mechanical analysis (DMA), and ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22774
更新日期：2012-02-01 00:00:00
abstract：:The geometry and structural features of the inclusion complexes of beta-cyclodextrin (beta-CD) with the chiral antiamnesic drugs (+/-)-1-benzyl-4-hydroxymethylpyrrolidin-2-one (WEB-1868). (+/-)-1-benzenesulfonyl-5-ethoxypyrrolidin-2-one (RU-35929), and (+/-)-1-(3-pyridinlysulfonyl)-5-ethoxypyrrolidin-2-one (RU-47010) ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600811205
更新日期：1992-12-01 00:00:00
abstract：:Because the ionized species is more polar than its un-ionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980433o
更新日期：1999-05-01 00:00:00
abstract：:A semi-automated protein binding assay using equilibrium dialysis (ED) and a novel mixed-matrix methodology has been developed. This method decreases mass spectrometer run time and reduces the likelihood of experimental artifacts. In this cassette-based approach, a single matrix is prepared following dialysis by mixin...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22188
更新日期：2010-12-01 00:00:00
abstract：:Previously, we reported that repeated oral treatment with etoposide (ETP) increased ileal membrane localization of P-glycoprotein (P-gp) and that this was possibly mediated by increased expression of the ezrin/radixin/moesin (ERM)/phosphorylated ERM (p-ERM) via activation of RhoA/ROCK. These changes caused decreases i...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23503
更新日期：2013-05-01 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：:An assay is described for the determination of the H2-receptor antagonist, cimetidine, in human plasma and urine. Alkalinized plasma or urine was extracted with methylene chloride, the organic phase was evaporated, and the reconstituted residue was analysed by high-pressure liquid chromatography (HPLC) using a reverse...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710528
更新日期：1982-05-01 00:00:00
abstract：:Plasma binding of chlordiazepoxide, diazepam, loraxepam, and oxazepam was determined by equilibrium dialysis in 20 male, healthy volunteers, 25-86 years old. A wide range of binding was observed, with the free fraction varying twofold for lorazepam, fourfold for chlordiazepoxide and diazepam, and over 20-fold for oxa...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600681034
更新日期：1979-10-01 00:00:00
abstract：:The chemical shifts of the methyl groups of 2,4-dimethylbenzo[g]quinoline are defined with respect to concentration, showing that the methyl resonances are reversed from their expected positions in concentrations normally used in NMR spectroscopy. The phenomenon is explained in terms of the probably "fixation" of bond...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660839
更新日期：1977-08-01 00:00:00
abstract：:The blood-brain barrier permeation has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A linear regression model was developed to predict the in vivo blood-brain partitioning coefficient on a data set of 119 compounds, treated as the logarithm of the blood-brain concentrat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20081
更新日期：2004-07-01 00:00:00
abstract：:An emerging technology subtype that has been adopted by formulators to address low-solubility issues is the supersaturating drug delivery system; this system is based on the "spring" and "parachute" design elements, which have been applied to lipid-based formulations, S(M)EDDS, solid dispersions, nano-based systems, a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22750
更新日期：2012-01-01 00:00:00
abstract：:A randomized, two-way, crossover study was performed on 18 normal volunteers to assess the influence of food on the bioavailability of lisinopril, (1-[N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl]-L-proline), a long-acting nonsulfhydryl angiotensin converting enzyme inhibitor. A single, 20-mg oral dose of lisinopril was ...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/jps.2600750416
更新日期：1986-04-01 00:00:00
abstract：:The aim of this study was to investigate the effect of divalent metal ions (Ca, Mg(2+) , and Zn(2+) ) on the stability of oxytocin in aspartate buffer (pH 4.5) and to determine their interaction with the peptide in aqueous solution. Reversed-phase high-performance liquid chromatography and high-performance size-exclus...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23546
更新日期：2013-06-01 00:00:00
abstract：:The purpose of the present study was to develop a physiologically based pharmacokinetic model for dextromethorphan (DEX) and its metabolites in extensive and poor metabolizers. The model was used to study the influence of dissolution rates on the sensitivity of maximum plasma concentration and area under the concentra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.09.036
更新日期：2019-01-01 00:00:00
abstract：:Biphenylalkyl monoesters of succinic and related acids represent a potent new class of cyclic AMP phosphodiesterase inhibitors. The biphenyl group is necessary for potent inhibition. The spatial relationship of the carboxyl and ester groups and alkyl chain length are important to inhibitory potency. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680732
更新日期：1979-07-01 00:00:00
abstract：:The majority of gene therapy clinical trials use plasmid DNA that is susceptible to shear-induced degradation. Many processing steps in the extraction, purification, and preparation of plasmid-based therapeutics can impart significant shear stress that can fracture the phosphodiester backbone of polynucleotides, and r...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.10140
更新日期：2002-07-01 00:00:00
abstract：:The presence of subvisible particles in formulations of therapeutic proteins is a risk factor for adverse immune responses. Although the immunogenic potential of particulate contaminants likely depends on particle structural characteristics (e.g., composition, size, and shape), exact structure-immunogenicity relations...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.01.015
更新日期：2018-05-01 00:00:00
abstract：:The solubilization of five model hydrophobic drugs by a series of micelle-forming, water-soluble methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymers (MePEG-b-PCL) with varying methoxy poly(ethylene glycol) (MePEG) and polycaprolactone (PCL) block lengths was investigated. Variation of the feed weig...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21037
更新日期：2008-03-01 00:00:00
abstract：:The diffusion model for percutaneous absorption is developed for the specific case of delivery to the skin being limited by the application of a finite amount of solute. Two cases are considered; in the first, there is an application of a finite donor (vehicle) volume, and in the second, there are solvent-deposited so...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/1520-6017(200104)90:4<504::aid-jps1008>3.0
更新日期：2001-04-01 00:00:00
