Abstract：
:The correlation between dynamic surface properties of drug molecules and drug absorption in two common in vitro models of the intestinal wall (Caco-2 monolayers and rat intestinal segments) has been investigated. A homologous series of beta-adrenoreceptor antagonists were used as model compounds. Dynamic molecular surface properties, considering all low-energy conformations, of the compounds were calculated. The flexibility of the molecules was studied by molecular mechanics calculations (MM2) and the van der Waals' (vdW), and water accessible surface areas were calculated and averaged according to a Boltzmann distribution. Excellent correlations were obtained between the dynamic polar vdW surface areas and cell permeabilities in Caco-2 cells and rat ileum (r2 = 0.99 and 0.92, respectively). These correlations were stronger than those between calculated octanol/buffer partition coefficients (log Doct,7.4) and permeability (r2 = 0.80 and 0.73, respectively). Moreover, the calculated log Doct,7.4 values failed to rank the permeability coefficients through Caco-2 monolayers and rat ileum in the correct order. The results indicate that dynamic polar surface area is a promising alternative model for the prediction of oral drug absorption.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Palm K,Luthman K,Ungell AL,Strandlund G,Artursson Pdoi
10.1021/js950285rsubject
Has Abstractpub_date
1996-01-01 00:00:00pages
32-9issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(15)49978-2journal_volume
85pub_type
杂志文章abstract：:The purpose of this study was to investigate the phase-sensitive delivery systems (D,L-polylactide in triacetin) for controlled delivery of insulin at basal level. The effect of varying concentration of zinc, polymer, and insulin on the in vitro release of insulin was evaluated. Stability of released insulin was inves...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22433
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abstract：:A single method for the quantitative determinations of three active ingredients, phenylephrine hydrochloride, phenylpropanolamine hydrochloride, and brompheniramine maleate, and one inactive ingredient (sodium benzoate) in a commercial product for colds is reported. The method is based on paired ion high-pressure liqu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670643
更新日期：1978-06-01 00:00:00
abstract：:Evaluation of a multiplexed capillary electrophoresis (CE) method for pK(a) measurements of organic compounds, including low solubility compounds, is presented. The method is validated on a set of 105 diverse compounds, mostly drugs, and results are compared to literature values obtained from multiple references. Two ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21287
更新日期：2008-07-01 00:00:00
abstract：:A method is reported for studying the effects of several factors at room temperature on the oxygen permeability of soft gelatin capsule shell films. The method involves the use of a permeability cell assembly and the spectrophotometric determïnation of oxygen with an alkaline pyrogallic acid solution. Factors investig...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640528
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abstract：:The degradation kinetics and mechanism of a potent new cephalosporin, cefotaxime sodium, in aqueous solution were investigated at pH 0-10 at 25 degrees and an ionic strength of 0.5. The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo first-order kinetics with...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720114
更新日期：1983-01-01 00:00:00
abstract：:The recently introduced four-parameter extended Hansen approach was used to study the solubility of p-hydroxybenzoic acid and methyl p-hydroxybenzoate in 32 and 35 individual solvents, respectively. The results are compared with those for benzoic acid in 40 solvents. Seventeen of the thirty-two or 53% of the calculate...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730211
更新日期：1984-02-01 00:00:00
abstract：:Topical lidocaine has been recently marketed as a new treatment for post-herpetic neuralgia. The aim of our study was to characterize the absorption profile of and systemic exposure to lidocaine from patch and gel formulations in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes ...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670122
更新日期：1978-01-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.10117
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journal_title：Journal of pharmaceutical sciences
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更新日期：1999-07-01 00:00:00
abstract：:Carboxy group-terminated synthetic polymers--branched poly(ethylene glycol), poly(acryloylmorpholine), and poly(vinylpyrrolidone)--were made amphiphilic by derivatization with phosphatidyl ethanolamine via the terminal carboxy group and then incorporated into lecithin-cholesterol liposomes prepared by the detergent di...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840904
更新日期：1995-09-01 00:00:00
abstract：:The interaction between sulfadimethoxine and tolbutamide in sheep involving displacement from protein binding sites was investigated quantitatively. A 52% increase in the unbound plasma concentration of tolbutamide was observed in vitro at 37 degrees after the addition of sulfadimethoxine (100 microgram/ml) to sheep p...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660803
更新日期：1977-08-01 00:00:00
abstract：:An automated potentiometric procedure was used for studying in vitro dissolution kinetics of acidic drugs. Theoretical considerations indicated that the pH-stat method could be used to establish approximate sink conditions or, possibly, a perfect sink. Data obtained from dissolution studies using the pH-stat method we...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670837
更新日期：1978-08-01 00:00:00
abstract：:The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulati...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600641218
更新日期：1975-12-01 00:00:00
abstract：:In vitro percutaneous permeation of betamethasone 17-valerate through excised human skin was studied. Pressure-sensitive silicone adhesive containing betamethasone 17-valerate in suspension was used as a vehicle. Steady-state flux through the split-thickness skin was similar to that through the isolated epidermis. How...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820504
更新日期：1993-05-01 00:00:00
abstract：:The thiazide diuretic chlorothiazide is poorly metabolized, and is predominantly excreted via the kidneys. We have previously shown that chlorothiazide is transported by ATP-binding cassette transporter G2, suggesting a potential role for this transporter in apical efflux of chlorothiazide in the kidney. However, beca...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.23491
更新日期：2013-05-01 00:00:00
abstract：:A α-helical GALA peptide (WEAALAEALAEALAEHLAEALAEALEALAA) has been found to possess dual functions: a pH-dependent inducer of endosomal escape, and a ligand that targets lung endothelium. In the present study, the flexibility of GALA was improved by modifying the edge with polyethylene glycol linker, to increase lung-...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.04.075
更新日期：2017-09-01 00:00:00
abstract：:A sensitive and specific GLC method is described to determine therapeutic levels of tilidine and its two main metabolites, nortilidine and bisnortilidine, in plasma and urine. The method involves the extraction of the compounds and an internal standard with cyclohexane from alkalinized samples, followed by back-extrac...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600671237
更新日期：1978-12-01 00:00:00
abstract：:The clearance (Cl) and volume of distribution (V(ss)) of a lipophilic, lymphatically transported drug, halofantrine (Hf) have been evaluated after intravenous delivery to the systemic circulation in ex vivo lymph and plasma, and compared with the data obtained after administration of a lipid-based emulsion and a lipid...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.23211
更新日期：2012-09-01 00:00:00
abstract：:Site I of human serum albumin is an important and complex region for high-affinity binding of drugs. Equilibrium dialysis showed independent binding of dansyl-L-asparagine (DNSA) and n-alkyl p-aminobenzoates (p-ABEs) to regions Ib and Ic, respectively, in the pH range 6.0-9.0. However, individual binding of DNSA incre...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20203
更新日期：2004-12-01 00:00:00
abstract：:Maintaining good content uniformity (CU) is a significant challenge for low-dose oral tablets in particular when using direct compression (DC). Using 6 model active pharmaceutical ingredients, we show that a platform DC tablet formulation suitable for developing low-dose API with excellent CU can be developed. This pl...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2017.03.005
更新日期：2017-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1002/jps.2600640337
更新日期：1975-03-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20941
更新日期：2007-05-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.017
更新日期：2020-01-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840914
更新日期：1995-09-01 00:00:00
abstract：:The mechanism of organic solvent evaporation during microencapsulation and its role during microsphere hardening has been investigated. Evaporation and encapsulation studies were carried out in a jacketed beaker, filled with aqueous hardening solution, which was maintained at constant temperature and constant stirring...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：
更新日期：1999-10-01 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：:Review of the current literature on racial differences in pharmacokinetics of drugs supports the premise that only pharmacokinetic processes which are biologically or biochemically mediated have the potential to exhibit differences between racial or ethnic groups. Thus, the pharmacokinetic factors which can be expecte...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1021/js9702168
更新日期：1997-12-01 00:00:00
abstract：:The use of intravascular tyrosine (TYR) to enhance catecholamine release in hemorrhagic shock and other cardiovascular diseases, or as a constituent of nutrient mixtures used for total parenteral nutrition, is limited by the unusually poor solubility of the amino acid in water. We have thus examined the ability of var...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790807
更新日期：1990-08-01 00:00:00
abstract：:The promoting efficacies of N-acyl derivatives of amino acids on the rectal absorption of sodium ampicillin were investigated using the rat rectal loop technique. N-Acyl derivatives with longer carbon chains in the acyl moiety showed a greater promoting potency. The promoting potencies of N-acyl derivatives of phenylg...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760703
更新日期：1987-07-01 00:00:00
