Abstract:
:One manifestation of cystic fibrosis (CF) is the presence of a viscid mucus secretion in the lungs. The clearance of this mucus is significantly slower than in "normals" due to uncoordinated beating of the cilia and the increased viscosity of the mucus. In these studies, the permeabilities of p-aminosalicylic acid, isoniazid, and pyrazinamide through unpurified CF respiratory mucus and through purified pig gastric mucus solutions were compared in order to evaluate the relative barrier properties of these mucus solutions. These model compounds, while not often used clinically in CF, are used in other pulmonary diseases and have the potential to be administered by inhalation delivery systems. Permeability studies were carried out in Side-Bi-Side diffusion cells fitted with a custom membrane holder capable of retaining the mucus solutions. Permeabilities through CF mucus solution and its fractions were compared to those measured through buffer and reconstituted purified pig gastric mucus. There were 28--75% decreases in drug permeability when pig gastric mucus was replaced by different CF mucus solutions. This indicates that optimal drug delivery directly to the lungs must take into account the decreased drug transport rate across diseased mucus in addition to drug loss due to binding to the glycoproteins or inefficient delivery via aerosolization. Transmission electron microscopy revealed minor differences in the glycoprotein strand structure between reconstituted pig gastric mucus and CF mucus primarily with regard to glycoprotein chain length and extent of branching. Similar viscoelastic behaviors between the CF gel fraction and synthetic CF mucus were observed. This model CF mucus system can simulate diseased mucus and can be utilized for in vitro studies to optimize drug permeability.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Bhat PG,Flanagan DR,Donovan MDdoi
10.1021/js950381ssubject
Has Abstractpub_date
1996-06-01 00:00:00pages
624-30issue
6eissn
0022-3549issn
1520-6017pii
S0022-3549(15)50081-6journal_volume
85pub_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::The pneumococcal histidine triad protein D (PhtD) is believed to play a central role in pneumococcal metal ion homeostasis and has been proposed as a promising vaccine candidate against pneumococcal disease. To investigate for potential stabilizers, a panel of physiologically relevant metals was screened using the the...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.06.003
更新日期:2017-10-01 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::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::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::In this study, we investigated the potential roles of nanoparticles (<100 nm) and submicron (100-1000 nm) particles in the formation of microparticles (>1000 nm) in protein formulations under some pharmaceutically relevant stress conditions. Exposure of intravenous immunoglobulin solutions to the interface-associated ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.03.016
更新日期:2018-07-01 00:00:00
abstract::In this work, a novel risk-based methodology for lot release is proposed. Its objective is to assess the risk that a lot declared to have passed truly meets product specifications. The methodology consists of 3 parts: adaptive sample size determination, estimation of the probability that the product was within specifi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2019.10.011
更新日期:2020-02-01 00:00:00
abstract::Cephalosporins are among the most frequently used broad-spectrum antimicrobial agents. Ceftazidime is a semisynthetic β-lactam antibiotic for parenteral administration widely used in the clinical practice, which has been categorized as a third-generation cephalosporin antibiotic. This drug crystallizes as a pentahydra...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2019.11.018
更新日期:2020-03-01 00:00:00
abstract::The fungal microorganism Cunninghamella echinulata was utilized to para-hydroxylate the synthetic substrate (+/-)-1-isopropylamino-3-phenoxy-propan-2-ol (1). The resulting product, (+/-)-1-(4-hydroxyphenoxy)-3-isopropylamino-propan-2-ol, or (+/-)-prenalterol, (2) was formed in greater than 85% yield. Extracts from inc...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600760220
更新日期:1987-02-01 00:00:00
abstract::A procedure for the determination of mianserin, desmethylmianserin, and 8-hydroxymianserin in plasma at therapeutic concentrations by liquid chromatography with electrochemical detection is described. Following a multiple-step extraction from alkaline plasma into methyl-tert-butyl ether, the reconstituted extract was ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600710812
更新日期:1982-08-01 00:00:00
abstract::Quantitative determination of serum concentrations of carvedilol [(+/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl) amino]-2-propanol], a combined alpha- and beta-adrenergic receptor antagonist, was obtained using HPLC with spectrofluorometric detection. Carvedilol was extracted from alkalinized serum with eth...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600751218
更新日期:1986-12-01 00:00:00
abstract::This study examined the safety, pharmacodynamic and pharmacokinetic similarity of the human recombinant filgrastim products ior®LeukoCIM and Neupogen® following a 28-day repeated subcutaneous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinica...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.02.009
更新日期:2017-06-01 00:00:00
abstract::In this work, the production of dexametasone and dexametasone acetate microparticles is proposed using supercritical-assisted atomization (SAA). This process is based on the solubilization of supercritical carbon dioxide in a liquid solution containing the drug; then, the ternary mixture is sprayed through a nozzle an...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20703
更新日期:2006-09-01 00:00:00
abstract::A theoretical investigation has been conducted to understand the deconvolution method used for evaluating the in vivo release rate of an oral controlled-release product from the plasma drug concentration versus time profile. The theory is based on well-accepted pharmacokinetic compartmental models. The cumulative amou...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600821116
更新日期:1993-11-01 00:00:00
abstract::An approach to analyzing and interpreting kinetic data from stability studies using factorial designs is presented. This may be useful for screening purposes or as an aid in identifying significant effects in complex systems. A typical 2n factorial experiment is discussed, and methods of variance estimation and statis...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600720410
更新日期:1983-04-01 00:00:00
abstract::A commercial dispersive Raman spectrometer operating at 785 nm with a CCD detector was used to acquire spectra of USP reference materials inside amber USP vials. The laser and collection beams were directed through the bottom of the vials, resulting in a 60% loss of signal. The Raman shift was calibrated with a 4-acet...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js970330q
更新日期:1998-01-01 00:00:00
abstract::The objectives of this study were to identify the key process parameters during steam granulation of disordered mesoporous silica material Syloid® 244 FP (244) and to compare two different binders: polyvinylpyrrolidone (PVP) K25 and hydroxypropylmethyl cellulose (HPMC). Itraconazole (ITZ) was selected as the model com...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23699
更新日期:2013-11-01 00:00:00
abstract::Samples of ethacrynic acid were treated with methanol-hydrochloric acid or with diazomethane. GLC and mass spectrometric analysis indicated that the methanol-hydrochloric acid reaction gave the expected methyl ester, whereas diazomethane treatment gave a compound containing an additional 14 mass units. Accurate mass m...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670728
更新日期:1978-07-01 00:00:00
abstract::The aim of the present work was to investigate the preparation of PLGA nanoparticles (PNP) and PLGA-Hp55 nanoparticles (PHNP) as potential drug carriers for oral insulin delivery. The nanoparticles were prepared by a modified emulsion solvent diffusion method in water, and their physicochemical characteristics, drug r...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20750
更新日期:2007-02-01 00:00:00
abstract::A thermodynamic analysis of the energy transformations occurring within pharmaceutical tablets during the unloading phase of compaction was performed on Avicel, calcium phosphate, acetaminophen, and calcium oxalate. This analysis was based on viscoelastic stress data collected using an instrumented rotary press and wa...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600830629
更新日期:1994-06-01 00:00:00
abstract::The binding of Cu2+ and Ni2+ to bovine, dog, and human serum albumin has been studied by the 35Cl NMR probe technique. The number of primary copper sites were estimated to be 1.3 for human serum albumin, 3.1 for bovine serum albumin, and 6.6 for dog serum albumin. A similar number of primary nickel sites was determine...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740116
更新日期:1985-01-01 00:00:00
abstract::A physiological flow model was developed for the distribution of sulfathiazole residues in various tissues in swine. The approach was compartmental, in which the compartments and equilibrium constants had physiological meaning. Differential equations were developed, and appropriate parameter values and initial conditi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600731107
更新日期:1984-11-01 00:00:00
abstract::Pretreatment with cyclosporine reportedly prolongs the effect of certain general anesthetics in humans and the sleeping time of mice after pentobarbital administration. This investigation was designed to determine the mechanism(s) of the cyclosporine-barbiturate interaction. Adult female Wistar rats received cyclospor...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600790106
更新日期:1990-01-01 00:00:00
abstract::An electron-capture GLC method was developed for measuring pindolol in human plasma and urine. The unchanged drug was extracted with benzene from alkalinized plasma or urine using propranolol as the internal standard. Both compounds subsequently were back-extracted into 0.1 M HCl and then into benzene. After evaporati...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600691019
更新日期:1980-10-01 00:00:00
abstract::High pressure liquid chromatography using reversed-phase and/or ion-pair techniques was used to optimize resolution of aspirin-containing muscle relaxant mixtures as well as other therapeutic agents commonly found in muscle relaxant-analgesic mixtures. The compounds were chromatographed on an octadecylsilane column us...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600680112
更新日期:1979-01-01 00:00:00
abstract::Fifteen pyrimidine-related compounds were evaluated for their ability to inhibit enzymatic degradation of 5-fluoro-2'-deoxyuridine (FUdR). Acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed the highest inhibitory effect on the phosphorolytic degradation of FUdR in various tissue homogenates derived fro...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600771108
更新日期:1988-11-01 00:00:00
abstract::Capillary gas chromatography using an open tubular fused silica column and NP-FID was applied to the simultaneous analysis of the antihistamine, carbinoxamine, and the antitussive, hydrocodone, in human serum. Carbinoxamine and hydrocodone were extracted into methylene chloride-2-propanol (9:1) under alkaline conditio...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600721126
更新日期:1983-11-01 00:00:00
abstract::The deamidation of asparagine into aspartate and isoaspartate moieties is a major pathway for the chemical degradation of monoclonal antibodies (mAbs). It can affect the shelf life of a therapeutic antibody that is not formulated or stored appropriately. A new approach to detect deamidation using ion exchange chromato...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23529
更新日期:2013-06-01 00:00:00
abstract::The hepatic distribution, biliary excretion, and mass balance of liposomal amphotericin B (L-AmB) were investigated in recirculated isolated perfused rat liver. The results were compared with those from the conventional AmB formulation, amphotericin B deoxycholate (D-AmB). L-AmB was introduced as a bolus into the perf...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20239
更新日期:2005-01-01 00:00:00
abstract::A stability-indicating reversed-phase high-performance liquid chromatographic method using a refractive index detector is described for the determination of propylene carbonate in pharmaceutical formulations. Good precision and accuracy of the method was demonstrated using an aqueous formulation. This method is also a...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740626
更新日期:1985-06-01 00:00:00