Influence of pH, temperature, and buffers on the kinetics of ceftazidime degradation in aqueous solutions.


:First-order rate constants (k) were determined for the hydrolysis of ceftazidime in the pH range of 0.5 to 8.5 at 45, 55, and 65 degrees C by a stability-indicating HPLC assay. In the absence of buffer effects, the pH-rate expression was k = kH1f1(aH+) + kH2f2(aH+) + kH3f3(aH+) + kSf3 + kOHf3(aOH-), where KH and KOH are the catalytic rate constants for the activity of hydrogen (aH+) and hydroxyl (aOH-) ions, respectively, and kS is the rate constant for spontaneous hydrolysis. The fractions of ceftazidime in various stages of dissociation (f1, f2, and f3) were calculated from kinetically determined apparent Ka values of 2.03 x 10(-2) and 4.85 x 10(-5). Catalytic constants (kcat) were calculated for formate, acetate, phosphate, and borate buffers, which accelerated hydrolysis. Each of the rate constants (kH1, kH2, kH3, kS, kOH, and kcat) were described as a function of temperature with calculated A and E values in the Arrhenius equation, kT = Ae-E/RT. Ceftazidime hydrolysis rate constants (k) were calculated as a function of pH, temperature, and buffer by combining the pH-rate expression with the buffer contributions calculated from kcat values and the temperature dependencies. These equations and their parameter values successfully calculated 95 of 104 experimentally determined rate constants with errors of < 10%. Maximum stability was observed in the relatively pH-independent region from 4.5 to 6.5. Hydrolysis rate constants at 30 degrees C were predicted and experimentally verified for four ceftazidime solutions, three of which (pH 4.4 acetate buffer and pH 5.5 and 6.5 phosphate buffers) maintained 90% of their initial concentration for approximately 1.5 days.


J Pharm Sci


Zhou M,Notari RE




Has Abstract


1995-05-01 00:00:00














  • Comparison of operational characteristics of different dissolution testing systems.

    abstract::Three dissolution apparatus, the rotating basket, the rotating paddle, and the rotating filter--stationary basket, were evaluated for their suitability as production control tools and their relation to blood level studies in dogs. The rotating basket and rotating paddle assemblies were easier to use and less variable ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hardwidge EA,Sarapu AC,Laughlin WC

    更新日期:1978-12-01 00:00:00

  • Binding of cosalane--a novel highly lipophilic anti-HIV agent--to albumin and glycoprotein.

    abstract::Cosalane is a potent inhibitor of HIV replication with multiple sites of action. The purposes of this study were to (a) determine the extent and nature of cosalane binding to mucin, alpha(1)-acid glycoprotein (AAG), plasma, and human (HSA) and bovine serum (BSA) albumin, and (b) determine the primary site(s) of cosala...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kuchimanchi KR,Ahmed MS,Johnston TP,Mitra AK

    更新日期:2001-05-01 00:00:00

  • Preparation and analysis of deuterium-labeled aspirin: application to pharmacokinetic studies.

    abstract::Inhibition of endogenous prostacyclin and thromboxane biosynthesis by aspirin is critically dose-dependent in humans. Gastrointestinal and hepatic hydrolysis may limit systemic availability of aspirin, especially in low doses, perhaps contributing to the biochemical selectivity of aspirin. Existing analytical methods ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Pedersen AK,FitzGerald GA

    更新日期:1985-02-01 00:00:00

  • Application of a Best Practice Approach Using Resonant Mass Measurement for Biotherapeutic Product Characterization.

    abstract::Characterizing and quantifying subvisible particles in protein drug products is critical to ensuring product quality. A variety of analytical methods are used to detect and make meaningful measurements of subvisible particles. Resonant mass measurement (RMM) is a novel technology that characterizes the subvisible part...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Krueger AB,Hadley J,Cheney PP,Markova N,Carpenter JF,Fradkin AH

    更新日期:2019-05-01 00:00:00

  • Interaction of metronidazole with metallic ions of biological importance.

    abstract::The possibility tht metronidazole exerts several of its biological actions via interaction with important metal ions was investigated. NMR spectroscopy and polarography (ac) were used to test for any interaction, to locate the probable sites for complexation, and to determine the molecular stoichiometry of any complex...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chien YW,Lambert HJ,Sanvordeker DR

    更新日期:1975-06-01 00:00:00

  • Understanding the Increased Aggregation Propensity of a Light-Exposed IgG1 Monoclonal Antibody Using Hydrogen Exchange Mass Spectrometry, Biophysical Characterization, and Structural Analysis.

    abstract::This work compares the conformational stability, backbone flexibility, and aggregation propensity of monomer and dimer fractions of an IgG1 monoclonal antibody (mAb) generated on UVA light exposure for up to 72 h collected by preparative size-exclusion chromatography, compared with unstressed control. UVA light exposu...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Bommana R,Chai Q,Schöneich C,Weiss WF 4th,Majumdar R

    更新日期:2018-06-01 00:00:00

  • GI absorption of beta-lactam antibiotics II: deviation from pH--partition hypothesis in penicillin absorption through in situ and in vitro lipoidal barriers.

    abstract::The absorption of propicillin from the rat stomach and small intestine in situ was examined as a function of recirculating solution pH. The in vitro interphase transport from an aqueous buffer of various pH values to the octanol phase was also studied for several penicillins by the use of a two-phase rolling cell. The...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Tsuji A,Miyamoto E,Hashimoto N,Yamana T

    更新日期:1978-12-01 00:00:00

  • Structural stability of vault particles.

    abstract::Vaults, at 13 MDa, are the largest ribonucleoprotein particles known. In vitro, expression of the major vault protein (MVP) alone in Sf9 insect cells results in the production of recombinant particles with characteristic vault structure. With the ultimate goal of using recombinant vaults as nanocapsules for the delive...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Esfandiary R,Kickhoefer VA,Rome LH,Joshi SB,Middaugh CR

    更新日期:2009-04-01 00:00:00

  • Alginate-Based Delivery Systems for Bevacizumab Local Therapy: In Vitro Structural Features and Release Properties.

    abstract::Alginate-based polyelectrolyte complexes (PECs) and hydrogel were engineered as platforms for local bevacizumab (BVZ) therapy. This study provides deep comprehension on the microstructures of such systems, and their correlation with drug-release patterns. PECs and hydrogel were characterized using Fourier transform in...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Ferreira NN,Caetano BL,Boni FI,Sousa F,Magnani M,Sarmento B,Ferreira Cury BS,Daflon Gremião MP

    更新日期:2019-04-01 00:00:00

  • Osmotic water transport through cellulose acetate membranes produced from a latex system.

    abstract::The advisability of a progressive curtailment of organic solvent film coating offers an incentive to develop latex systems. Here, the use of aqueous colloidal dispersions of cellulose acetate, plasticized with water-soluble additives, is proposed as an alternative way to obtain cellulose acetate membranes either by ca...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Bindschaedler C,Gurny R,Doelker E

    更新日期:1987-06-01 00:00:00

  • Use of fractal geometry to determine effects of surface morphology on drug dissolution.

    abstract::We extend and modify the Noyes-Whitney equation and the Hixon-Crowell cube root law to include surface roughness effects on the dissolution rate of drugs. The problem is treated theoretically in terms of the fractal reaction dimension, DR, of the effective surface which undergoes dissolution. Effects of changes in DR ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Farin D,Avnir D

    更新日期:1992-01-01 00:00:00

  • Irreversible aggregation of recombinant bovine granulocyte-colony stimulating factor (bG-CSF) and implications for predicting protein shelf life.

    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 th...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Roberts CJ,Darrington RT,Whitley MB

    更新日期:2003-05-01 00:00:00

  • Anthrax vaccine powder formulations for nasal mucosal delivery.

    abstract::Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a r...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Jiang G,Joshi SB,Peek LJ,Brandau DT,Huang J,Ferriter MS,Woodley WD,Ford BM,Mar KD,Mikszta JA,Hwang CR,Ulrich R,Harvey NG,Middaugh CR,Sullivan VJ

    更新日期:2006-01-01 00:00:00

  • Spectrophotometric determination of cycloserine with 9-methoxyacridine.

    abstract::Spectrophotometric assay for cycloserine based on the interaction of the drug with 9-methoxyacridine as a chromogenic agent is described. The highly colored substituted acridine product was identified as 9-(d-4-imino-3-isoxazolidinone)acridine. Color development was affected by time and temperature of heating and by t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Stewart JT,Yoo GS

    更新日期:1988-05-01 00:00:00

  • Utilising Magnetically Isolated Lysosomes for Direct Quantification of Intralysosomal Drug Concentrations by LC-MS/MS Analysis: An Investigatory Study With Imipramine.

    abstract::Lysosomes are acidic intracellular organelles that can extensively sequester basic lipophilic drugs due to pH and membrane partitioning, and therefore may significantly influence subcellular drug concentrations. Current in vitro methods for lysosomal drug sequestration evaluation typically lack the ability to accurate...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Francis L,Harrell A,Hallifax D,Galetin A

    更新日期:2020-09-01 00:00:00

  • Dosage intervals based on mean residence times.

    abstract::It is shown that a suitable dosage interval, tau, can be estimated by a factor times the sum of the mean residence time (MRT) of the central compartment (MRTC) and the MRT of the absorption site (MRTA). This value of tau will provide a ratio, maximum steady-state plasma concentration: minimum steady-state plasma conce...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wagner JG

    更新日期:1987-01-01 00:00:00

  • Disposition of norgestimate in the presence and absence of ethinyl estradiol after oral administration to humans.

    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


    authors: Weintraub HS,Abrams LS,Patrick JE,McGuire JL

    更新日期:1978-10-01 00:00:00

  • Protection of bovine serum albumin from aggregation by Tween 80.

    abstract::In an attempt to explain the mechanism of protein stabilization conferred by detergents, we investigated the effect of Tween 80 on aggregation of bovine serum albumin (BSA) using circular dichroism (CD) and native gel electrophoresis. CD thermal scans showed that BSA denatures at about 54 degrees C in 20 mM Tris, pH 7...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Arakawa T,Kita Y

    更新日期:2000-05-01 00:00:00

  • Antidermatitic perspective of hydrocortisone as chitosan nanocarriers: an ex vivo and in vivo assessment using an NC/Nga mouse model.

    abstract::The aim of this study to administer hydrocortisone (HC) percutaneously in the form of polymeric nanoparticles (NPs) to alleviate its transcutaneous absorption, and to derive additional wound-healing benefits of chitosan. HC-loaded NPs had varied particle sizes, zeta potentials, and entrapment efficiencies, when drug-t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hussain Z,Katas H,Amin MC,Kumulosasi E,Sahudin S

    更新日期:2013-03-01 00:00:00

  • Nasal absorption of dihydroergotamine from liquid and powder formulations in rabbits.

    abstract::Nasal drug delivery is an interesting route of administration for dihydroergotamine in migraine therapy. The currently available formulation contains dihydroergotamine at 4 mg/mL. For a nasal dose of 2 mg, a volume of 0.5 mL has to be administered, which sometimes leads to spillage of the formulation. The aim of the p...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Marttin E,Romeijn SG,Verhoef JC,Merkus FW

    更新日期:1997-07-01 00:00:00

  • Ocular pharmacokinetics of a novel tetrahydroquinoline analog in rabbit: absorption, disposition, and non-compartmental analysis.

    abstract::The pharmacologically active compound (33% reduction in rabbit intraocular pressure recovery rate assay) 1-ethyl-6-fluoro-1,2,3,4-tetrahydroquinoline (MC4), which showed ocular hypotensive action and had optimum physicochemical properties, was characterized for its ocular absorption and distribution properties to bett...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Pamulapati CR,Schoenwald RD

    更新日期:2011-12-01 00:00:00

  • Investigation of Dose-Dependent Factors Limiting Oral Bioavailability: Case Study With the PI3K-δ Inhibitor.

    abstract::It is understood that a potential issue for drugs with poor aqueous solubility is low oral absorption. If oral exposure issues arise when working with a low solubility drug candidate, the common action is to rely on enabling formulations to solve the issue. However, this approach becomes troublesome in the pre-clinica...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chiang PC,Sutherlin D,Pang J,Salphati L

    更新日期:2016-06-01 00:00:00

  • Role of benzyl alcohol in the unfolding and aggregation of interferon α-2a.

    abstract::Benzyl alcohol (BA) is the most widely used antimicrobial preservative in multidose protein formulations, and has been shown to cause protein aggregation. Our previous work on a model protein cytochrome c demonstrated that this phenomenon occurs via partial unfolding. Here, we examine the validity of these results by ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Bis RL,Singh SM,Cabello-Villegas J,Mallela KM

    更新日期:2015-02-01 00:00:00

  • Effect of dispersion on the coloring properties of aluminum dye lakes.

    abstract::The effect of particle size on the coloring properties of aluminum dye lakes was studied. Lakes impart color by dispersion in the medium to be colored. Dispersion techniques were developed, using scanning electron micrographs for particle sizing. The color strength and the trichromatic colorimetric properties were cal...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wou LL,Mulley BA

    更新日期:1988-10-01 00:00:00

  • Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin click clusters.

    abstract::To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Le HT,Jeon HM,Lim CW,Kim TW

    更新日期:2014-10-01 00:00:00

  • Simple and rapid determination of a new pharmaceutically active amine hydrochloride.

    abstract::The quantitative analysis of a new pharmaceutically active amine hydrochloride is described. Samples are extracted with chloroform. A yellow amine-dye complex is formed by buffering a sample-bromthymol blue solution at pH 8.5 +/- 0.1 and subsequently extracted with chloroform. The complex is treated with 0.01 N NaOH t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chang ZL,Papendick VE

    更新日期:1976-10-01 00:00:00

  • Cardiovascular effects of two potential beta-hydroxylase inhibitors.

    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


    authors: Venugopalan CS,Jenkins HJ

    更新日期:1985-06-01 00:00:00

  • Stable isotope coadministration methodology for the estimation of the fraction of imipramine metabolized to desipramine.

    abstract::The application of a stable isotope coadministration technique for estimating the fraction (fm) of imipramine (IP) that is converted to desipramine (DMI) is described. Four healthy male subjects received 25 mg of IP-d4 hydrochloride orally with 25 mg of DMI hydrochloride. The plasma concentrations of IP-d4, DMI-d4, an...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Sasaki Y,Shinohara Y,Baba S

    更新日期:1990-02-01 00:00:00

  • Nanoparticle formation of organic compounds with retained biological activity.

    abstract::Many pharmaceuticals are formulated as powders to aid drug delivery. A major problem is how to produce powders having high purity, controlled morphology, and retained bioactivity. We demonstrate the use of supercritical carbon dioxide as an antisolvent for meeting this need for two model drug systems, quercetin, a spa...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Jacobson GB,Shinde R,McCullough RL,Cheng NJ,Creasman A,Beyene A,Hickerson RP,Quan C,Turner C,Kaspar RL,Contag CH,Zare RN

    更新日期:2010-06-01 00:00:00

  • Molecular Dynamics of Amorphous Sulfamethazine With Structurally Related Sulfonamide Impurities Evaluated Using Thermal Analysis.

    abstract::In this study, the effects of structurally related organic impurities on the molecular dynamics of amorphous sulfamethazine were evaluated using thermal analysis. Sulfanilamide (SNA), sulfamerazine (SMR), and sulfadimethoxine were used as virtual impurities of sulfamethazine. The amorphous state was prepared in situ i...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hamada Y,Ono M,Ohara M,Yonemochi E

    更新日期:2017-04-01 00:00:00