Abstract：
:The acidic, neutral, and alkaline degradations of six therapeutically useful cephalosporins (cephalothin, cephaloridine, cephaloglycin, cephalexin, cephradine, and cefazolin), 7-amino-cephalosporanic acid, 7-aminodeacetoxycephalosporanic acid, and some 7-substituted derivatives were followed by high-pressure liquid chromatographic, UV spectrometric, iodometric, and hydroxamic acid assays. The pH-rate profiles were determined at 35 degrees and mu = 0.5. The acidic degradation pathway for the 3-acetoxymethyl and 3-pyridinylmethyl derivatives was the specific hydrogen-ion-catalyzed hydrolysis of the beta-lactam bonds. The beta-lactam hydrolyses of these antibiotics exhibited half-lives of about 25 hr at pH 1.0 and 35 degrees. The acetyl functions of 3-acetoxymethylcephalosporins were hydrolyzed eight times faster than their beta-lactam moieties to yield the corresponding deacetyl intermediates, which were rapidly converted to the lactones. Deacetoxycephalosporins were fairly acid stable; e.g., cephalexin and cephradine were about 25 times more stable than cephalothin, cephaloridine, and cephaloglycin and about 180 times more stable than ampicillin at pH 1.0. In the neutral degradation of 3-acetoxymethyl compounds, the competitive reactions of the direct water attack and intramolecular catalysis by the side-chain amido upon the beta-lactams were proposed. The pH-rate profiles near pH 8 for cephaloglycin, cephalexin, and cephradine could be explained by the intramolecular-nucleophilic attack of the side-chain alpha-amino group upon the beta-lactam carbonyls to produce diketopiperazine-type compounds. The reactivity of the cephalosporins in the hydroxideion-catalyzed degradation was influenced significantly by the C-3 methylene substituents.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Yamana T,Tsuji Adoi
10.1002/jps.2600651104subject
Has Abstractpub_date
1976-11-01 00:00:00pages
1563-74issue
11eissn
0022-3549issn
1520-6017pii
S0022-3549(15)39030-4journal_volume
65pub_type
杂志文章abstract：:The major objective of this study was to investigate and characterize the solution properties of cromolyn sodium (in D(2)O or D(2)O/H(2)O phosphate buffer at pH 7.5) using nuclear magnetic resonance (NMR) spectroscopy. The self-association of cromolyn molecules was examined primarily via one-dimensional (1)H and (13)C...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20034
更新日期：2004-05-01 00:00:00
abstract：:The release kinetics of a polymeric-controlled release device are determined by its geometry and dimensions. A method to calculate the required size and shape of diffusion-controlled dosage forms to achieve a particular release profile is presented. The diffusion parameters are determined for various drugs (theophylli...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980006a
更新日期：1998-07-01 00:00:00
abstract：:Currently, conjunctivitis is treated by frequent high dose administration of sparfloxacin eye drop solution. However, the eye drops are inconvenient because of low bioavailability, short ocular drug residence time, and need of frequent instillation, which lead to patient noncompliance affecting the routine life style ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2020.02.008
更新日期：2020-06-01 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：:The aim of this study was to determine the sensitivity of transgenic immune tolerant mice for the type and level of aggregation of recombinant human interferon alpha2b (rhIFNalpha2b). RhIFNalpha2b was aggregated by metal-catalyzed oxidation or by incubation at elevated temperature and various pHs. Native rhIFNalpha2b ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20599
更新日期：2006-05-01 00:00:00
abstract：:Both developing (Days --1-+12 relative to inoculation) and established (Days +18-+29) stages of Mycobacterium butyricum adjuvant-induced polyarthritis in rats were treated orally with cryogenine (100 mg/kg/day), a prototype anti-inflammatory (phenylbutazone, 100 mg/kg/day), or a prototype immunosuppressive (cyclophosp...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660925
更新日期：1977-09-01 00:00:00
abstract：:A rapid, sensitive, and specific determination of ketoprofen in human and animal deproteinized body fluids by reversed-phase high-pressure liquid chromatography is presented. The acid is detectable in amounts as low as 0.1 microgram/ml. Limits of error are in the range of +/- 5.1% of the sample mean. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680330
更新日期：1979-03-01 00:00:00
abstract：:Solubilization of nonpolar drugs constitutes one of the most important tasks in parenteral formulations design. This study investigates and assesses the solubility enhancement of Fluasterone by various techniques including cosolvency, micellization, and complexation. Of the solubilizing agents used, the modified beta-...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9901413
更新日期：1999-10-01 00:00:00
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：: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
doi：10.1002/jps.2600771011
更新日期：1988-10-01 00:00:00
abstract：:HPLC analysis confirmed a difference in the chemical composition of commercial versus NF reference standard potassium guaiacolsulfonate. After separation by fractional crystallization, the two constituents comprising the former sample were identified by 1H-NMR as potassium guaiacol-4- and -5-sulfonate, respectively. T...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730911
更新日期：1984-09-01 00:00:00
abstract：:A sensitive, specific high-performance liquid chromatographic procedure was developed for the determination of plasma ethmozin levels. Basic plasma samples were partitioned with methylene chloride. The organic extract was washed with water and then evaporated to dryness under reduced pressure. The residue was redissol...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600700433
更新日期：1981-04-01 00:00:00
abstract：:The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid be...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830327
更新日期：1994-03-01 00:00:00
abstract：:Sugars and polyols have been used routinely with lyophilized proteins and peptides as bulking agents, cryoprotectants, and lyoprotectants. However, reducing sugars may present a problem as excipients since they are potentially reactive with proteins. In this stability study of recombinant human relaxin (Rix) with vari...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js950456s
更新日期：1996-08-01 00:00:00
abstract：:Quantification analysis with near-infrared (NIR) spectroscopy typically requires utilizing chemometric techniques, such as partial least squares (PLS) method, to achieve the desired selectivity. This article points out a major limitation of these statistical-based calibration methods. The limitation is that the techni...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21482
更新日期：2009-03-01 00:00:00
abstract：:In relation to drug release properties the lateral and rotational mobility of two drugs and one drug mimic in photopolymerized poly(ethylene glycol) diacrylate (PEGDA) networks were investigated by nuclear magnetic resonance as a function of the network cross-link density and temperature. The network mesh size affects...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21251
更新日期：2008-08-01 00:00:00
abstract：:Drug transporters expressed in liver and kidney play a critical role in the elimination of a wide range of drugs and xenobiotics and inhibition of these transporters may therefore cause clinically significant drug-drug interactions (DDIs). Currently, in vitro transporter inhibition data are used to assess the risk tha...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2017.04.007
更新日期：2017-09-01 00:00:00
abstract：:Virtually all biological variables, including those affected by drugs, are subject to adaptive self regulation. In the description of the pharmacodynamics (PD) of drugs, it may be necessary to consider the endogenous control system (ECS) as an integral part of the PD. A PDECS model based on system analysis principles ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820310
更新日期：1993-03-01 00:00:00
abstract：:The dissolution rates of a number of drug-urethan solid-state dispersion systems were studied. A marked enhancement of the initial dissolution rates of several poorly water-soluble drugs was found when they were incorporated into a urethan matrix by heat fusion. These differences were considerable when pure substances...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670332
更新日期：1978-03-01 00:00:00
abstract：:The effect of variable protein binding (taken as independent parameter) on pharmacological activity of drugs is considered in terms of the exposure or the steady state concentration of unbound drug at targeted tissue. Based on the application of the parallel tube or dispersion models it is shown that for the most comm...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21958
更新日期：2010-04-01 00:00:00
abstract：:Some coated aspirin tablet formulations were evaluated by relating their properties to disintegrating force development patterns. The treatment of disintegrating force-time curves was effected using the Weibull distribution as proposed for dissolution. Such parameters as the maximum disintegrating force developed, the...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730531
更新日期：1984-05-01 00:00:00
abstract：:The objective of this work was to delineate the contribution of thermodynamic activities of ionized and unionized species on buccal drug permeation. The flux and permeability of a model acidic (nimesulide) and basic (bupivacaine) drug were determined across porcine buccal mucosa at different pH conditions. Thermodynam...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21301
更新日期：2008-10-01 00:00:00
abstract：:Pepsin adsorbed on gibbsite or boehmite, non-acid-reactive forms of aluminum hydroxide, had a significantly lower activity than pepsin in solution. IR and desorbed pepsin activity studies showed that the reduced activity of adsorbed pepsin was not due to denaturation of pepsin on adsorption. Steric occlusion of the ac...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600731105
更新日期：1984-11-01 00:00:00
abstract：:The results of this study show that pentamidine isethionate (PI) can exist in at least four crystalline forms-three anhydrates designated as forms A, B, and C, and a trihydrate. Form C is the high-temperature modification, produced by heating forms A, B, and the trihydrate above 130 degrees C and cannot be produced un...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970342b
更新日期：1998-09-01 00:00:00
abstract：:The reaction kinetics of blue tetrazolium with selected arylhydrazines were investigated under pseudo-first-order conditions. The reaction rate constants were obtained at various temperatures, and the enthalpy (8.4-11.2 kcal/mole) and entropy (-38--45 eu) of activations were calculated. A Hammett plot yielded a straig...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670714
更新日期：1978-07-01 00:00:00
abstract：:Transformation of polymorph I of clopidogrel hydrogen sulfate (CHS) to polymorph II of CHS during the crystallization was monitored by using in situ measurement of ultrasonic velocity. Drowning-out crystallization using methanol as a solvent and isopropyl alcohol as nonsolvent was carried out. The polymorphs were iden...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21313
更新日期：2008-10-01 00:00:00
abstract：:Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.07.008
更新日期：2018-11-01 00:00:00
abstract：:The stability of therapeutic proteins formulated in prefilled syringes (PFS) may be negatively impacted by the exposure of protein molecules to silicone oil-water interfaces and air-water interfaces. In addition, agitation, such as that experienced during transportation, may increase the detrimental effects (i.e., pro...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23973
更新日期：2014-06-01 00:00:00
abstract：:The reactions of omeprazole, a potent proton pump inhibitor (PPI), were investigated in the absence of a nucleophile. Reactions were monitored, using differential pulse polarography (DPP) at the static mercury drop electrode (SMDE), in solutions buffered to pH values ranging from 2.0 to 8.0. The fast, sensitive, and s...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20546
更新日期：2006-02-01 00:00:00
abstract：:The degradation kinetics of phentolamine hydrochloride in aqueous solution over a pH range of 1.2 to 7.2 and its stability in propylene glycol- or polyethylene glycol 400-based solutions were investigated. The observed rate constants were shown to follow apparent first-order kinetics in all cases. The pKa determinatio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600771116
更新日期：1988-11-01 00:00:00
