Abstract：
:The kinetics of irreversible aggregation of bovine Granulocyte-Colony Stimulating Factor (bG-CSF) in solution were investigated as a function of temperature (T), concentration, and pH, and analyzed in terms of an Extended Lumry-Eyring model of protein aggregation proceeding via a non-native conformational state. In the spirit of classic Lumry-Eyring models, the observed kinetics are separated into contributions from thermodynamic or conformational stability of unaggregated native and non-native states, and the intrinsic aggregation kinetics of non-native molecules. It is found that a detailed treatment of the intrinsic kinetics coupled with a two-state approximation of the reversible unfolding transition is sufficient to allow quantitative prediction of low-T stability from high-T data despite highly non-Arrhenius kinetics. Accounting for shifts in conformational equilibrium quantitatively captures the non-Arrhenius T dependence, without requiring the assumption of a change in the rate-determining step with T. From a more general perspective, the observed aggregation behavior of bG-CSF is consistent with the rate-determining step being aggregation at T below a crossover temperature T(x) that is inversely related to initial protein concentration. Above T(x), irreversible unfolding is presumably the rate-determining step. The results illustrate that protein aggregation kinetics can, in principle, be predicted quantitatively from so-called accelerated data provided the thermodynamic and kinetic components can be separately extrapolated to longer term storage conditions.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Roberts CJ,Darrington RT,Whitley MBdoi
10.1002/jps.10377subject
Has Abstractpub_date
2003-05-01 00:00:00pages
1095-111issue
5eissn
0022-3549issn
1520-6017pii
S0022-3549(16)36310-9journal_volume
92pub_type
杂志文章abstract：:Recent in vitro and in vivo studies have suggested transscleral iontophoresis as a means for non-invasive drug delivery to the eye. However, there remains a lack of information of the iontophoretic transport behavior of the sclera. The objective of the present study was to investigate the effects of permeant concentra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20293
更新日期：2005-04-01 00:00:00
abstract：:A computational approach which concomitantly determines the capacity-limited rate constants of parent drug elimination and metabolite formation is presented. The approach applies both the presently derived total excretory recovery versus dose relationships of the metabolite and the AUC versus dose relationships of the...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600791012
更新日期：1990-10-01 00:00:00
abstract：:The aim of the present work was to prepare and characterize chitosan-stearic acid conjugate nanomicelles for encapsulation of amphotericin B (AmB) and to evaluate the in vitro nebulization of the formulations. Water soluble chitosan was grafted to stearic acid (SA) chains via 1-ethyl-3-(3-dimethylaminopropyl)carbodiim...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22274
更新日期：2011-01-01 00:00:00
abstract：:Accelerated stability studies (37 degrees, 47 degrees, and 57 degrees) were conducted on buffered aqueous solutions (pH 7.4, 8.4, and 9.4) of hydrocortisone in the presence of various molar ratios of D-fructose. First-order degradation was observed. Significant improvement in hydrocortisone stability was seen in those...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720930
更新日期：1983-09-01 00:00:00
abstract：:The permeability coefficient, Kp, of pure unbranched alkanoic acids (C2-C7) applied to isolated porcine skin, reached a maximum in the solubility parameter (delta 2) range of 9.7-10 cal1 /2/cm3/2. When these and other penetrants were delivered from a solvent vehicle, the following linear relationships could be demonst...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730426
更新日期：1984-04-01 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：:Cationic antimicrobial peptides are good candidates for new diagnostics and antimicrobial agents. They can rapidly kill a broad range of microbes and have additional activities that have impact on the quality and effectiveness of innate responses and inflammation. Furthermore, the challenge of bacterial resistance to ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.21034
更新日期：2008-05-01 00:00:00
abstract：:Though there is an advantage in using the higher solubility amorphous state in cases where low solubility limits absorption, physical instability poses a significant barrier limiting its use in solid oral dosage forms. Unlike chemical instability, where useful accelerated stability testing protocols are common, no met...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.21138
更新日期：2008-04-01 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：:Mathematical models were determined relating preservative concentration and D values (decimal reduction times at 25 degrees C; pH 6.9-7.1) against Escherichia coli in aqueous medium. Preservatives investigated were 2-bromo-2-nitro-1,3-propanediol (Bronopol), N-(hydroxymethyl)-N-(1,3-dihydroxymethyl-2, 5-dioxo-4-imidaz...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740820
更新日期：1985-08-01 00:00:00
abstract：:Pharmaceutical aerosols are used to treat many pulmonary diseases. The use of low-density powders has proven useful to support efficient drug delivery. Measurements must account for the low-density, spherical particle features contributing to aerodynamic behavior. Ideally, the aerodynamic particle size distribution (A...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.11.005
更新日期：2018-03-01 00:00:00
abstract：:Oxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20632
更新日期：2006-08-01 00:00:00
abstract：:Hydrolytic degradation products of cefdinir were studied in acidic (pH 1), neutral (pH 6), and basic (pH 9) solutions. Seven major degradation products were isolated by preparative and/or high-performance liquid chromatography and characterized by UV, IR, 1H-NMR, and mass spectra. To clarify degradation pathways in ea...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js950446r
更新日期：1996-09-01 00:00:00
abstract：:A pharmacokinetic model that permits prediction of aqueous humor pilocarpine levels following topical application to rabbit eyes was developed. The model is able to account for changes in both instilled solution volume and drug concentration. The model, although simplified, relies mainly on experimentally verifiable a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670507
更新日期：1978-05-01 00:00:00
abstract：:The plasma protein binding of zomepirac, a new nonnarcotic analgesic, was studied using equilibrium dialysis. Experiments were performed using human plasma and plasma from mice, rats, and rhesus monkeys, all species of pharmacological or toxicological interest. At concentrations approximating those achieved in vivo, t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600700733
更新日期：1981-07-01 00:00:00
abstract：:In vitro iontophoretic administration of drugs through a microporous polyolefin membrane with hydrophilic urethane polymerfilled pores was done for the ionized drugs dexamethasone sodium phosphate, hydrocortisone sodium phosphate, and prednisolone sodium succinate, and for a nonionizable drug cortisone acetate. Curren...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780308
更新日期：1989-03-01 00:00:00
abstract：:The hydrolytic degradation of pirbuterol was investigated under saturated oxygen conditions over a wide range of pH values and at different temperatures. Two of the five observed breakdown products were positively identified. The first-order decomposition rate appeared to depend on the rate constants of the four disso...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660620
更新日期：1977-06-01 00:00:00
abstract：:Angiogenesis, the sprouting of capillaries from preexisting ones, is essential for the sustained growth of solid tumors. In this study, we used SU5416, a hydrophobic molecule with potent tyrosine kinase inhibitor of type 2 receptor for vascular endothelial growth factor (VEGF), as PEGylated emulsion (SU5416-PE), and e...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24071
更新日期：2014-08-01 00:00:00
abstract：:The in vitro uptake study was performed using the isolated cells of human oral mucosa, buccal and the dorsum of the tongue, to investigate the mechanisms of glucose uptake. The uptake of D-glucose was much larger in cells of the dorsum of the tongue than in buccal cells and was inhibited more extensively by 2-deoxy-D-...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
doi：10.1021/js980298f
更新日期：1999-08-01 00:00:00
abstract：:The solubility of phenacetin was determined at five temperatures in solvent mixtures of aprotic-amphiprotic mixtures of dioxane and water. Enthalpy-entropy compensation analysis is used to study the effect of changing polarity of the medium on the solute. The apparent heats of solution and free energies of solution ar...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js950497o
更新日期：1996-10-01 00:00:00
abstract：:The Setschenow constant, K(salt), of a nonelectrolyte in a NaCl solution is shown to be related to the logarithm of its octanol-water partition coefficient, log K(ow), determined by K(salt) = A log K(ow) + B, where K(ow) is the octanol-water partition coefficient of the solute and the coefficients A and B are constant...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/1520-6017(200012)89:12<1620::aid-jps13>3.0
更新日期：2000-12-01 00:00:00
abstract：:The purpose of this study was to evaluate the therapeutic efficacy of a new calcium phosphate (CaP)-based formulation in improving the bone mineral deficiency in ovariectomized (OVX) rats. The ions release experiments for CaP preparations (G2: 0.46% Mg, 5.78% Zn, and 2.5% F; G3:3.1% Mg, 0.03% Zn, and 3.01% F; G4: 1.25...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21131
更新日期：2008-01-01 00:00:00
abstract：:Some N,N'-bis(3-substituted benzylideneaminopropyl) piperazines were synthesized and characterized by their sharp melting points and elemental analyses. These substituted piperazines possessed anti-inflammatory activity, and the protection afforded by these compounds against carrageenan-induced edema ranged from 23 to...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650323
更新日期：1976-03-01 00:00:00
abstract：:Antisense phosphorodiamidate Morpholino oligomers (PMO) are resistant to degradation by cellular hydrolases, DNases, RNases, and phosphodiesterases, but remain sensitive to prolonged exposure to low pH. The present studies evaluate the oral fractional bioavailability, stability, and efficacy of two distinct PMO sequen...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10088
更新日期：2002-04-01 00:00:00
abstract：:Small particles of two steroids, cholesteryl acetate and beta-sitosterol, were prepared by the following technique. The steroid was dissolved in an organic solvent, which was emulsified in water in the presence of surfactant, thus giving a water-continuous emulsion. As the organic solvent was evaporated, the steroid p...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820608
更新日期：1993-06-01 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：:Levemopamil was solubilized by varying the concentration of hydroxypropyl-beta-cyclodextrin (HPbetaCD) and by the alteration of pH. The drug molecule has two sites for possible complexation with HPbetaCD, creating the possibility of either 1:1 or 1:2 complexation. The solubility as a function of HPbetaCD concentration...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9802143
更新日期：1998-12-01 00:00:00
abstract：:Unlike most organic compounds, both digoxin and digitoxin melted over a wide temperature range, with the widest range being 88 and 33 degrees for both compounds, respectively. Furthermore, the melting ranges varied markedly among several untriturated powders obtained from commercial sources and after recrystallization...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600681008
更新日期：1979-10-01 00:00:00
abstract：:Surface activity and critical micelle concentrations are reported for two diuretic drugs, furosemide and triamterene. The drugs generate a liquid membrane on a supporting membrane. Transport of chloride, sodium, and potassium ions through the liquid membranes generated by the drugs was studied. The data suggest that t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600731123
更新日期：1984-11-01 00:00:00
abstract：:Solubilities in isoctane and water were determined for several C1-phenolic esters of prostaglandin F2 alpha and prostaglandin E2 and acetates having the same phenol moiety. Linear free energy relationships for solubility among the series were observed with slopes of approximately 1. These results suggest that the cont...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690417
更新日期：1980-04-01 00:00:00
