Solubility profiling of HIV protease inhibitors in human intestinal fluids.


:The present study pursued to profile the intestinal solubility of nine HIV protease inhibitors (PIs) in fasted- and fed-state human intestinal fluids (FaHIF, FeHIF) aspirated from four volunteers. In addition, the ability of fasted- and fed-state simulated intestinal fluids (FaSSIF, FeSSIF) to predict the intestinal solubility was evaluated. All PIs were poorly soluble in FaHIF (from 7 μM for ritonavir to 327 μM for darunavir) and FeHIF (from 15 μM for atazanavir to 409μM for darunavir). For four of nine PIs, food intake significantly enhanced the solubilizing capacity of intestinal fluids (up to 18.4-fold increase for ritonavir). The intersubject variability (average coefficient of variance CVfed = 60.6%, CVfasted = 40.4%) was higher as compared with the intrasubject variability (CVfed = 41.3%, CVfasted = 20.5%). PI solubilities correlated reasonably well between FaSSIF and FaHIF (R = 0.817), but not between FeSSIF and FeHIF (R = 0.617). To conclude, postprandial conditions increased the inter- and intrasubject variability of the PIs. The inability of FeSSIF to accurately predict the FeHIF solubility emphasizes the need for a multivariate approach to determine solubility profiles, taking into account solid-state characteristics, pH, mixed bile acid/phospholipid micelles, and digestive products.


J Pharm Sci


Wuyts B,Brouwers J,Mols R,Tack J,Annaert P,Augustijns P




Has Abstract


2013-10-01 00:00:00














  • Fluorescence assay of nitrofurantoin with o-aminothiophenol in plasma and urine.

    abstract::A fluorescence method is presented for the determination of nitrofurantoin based on conversion of the drug to a fluorescent substance. The method requires 0.1-0.5 ml of plasma or diluted urine and is 10 times more sensitive than the commonly used colorimetric method. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Watari N,Funaki T,Kaneniwa N

    更新日期:1980-01-01 00:00:00

  • Synthesis and characterization of surface-hydrophobic ion-exchange microspheres and the effect of coating on drug release rate.

    abstract::Biodegradable, dextran-based ion-exchange microspheres (IE-MS) have been used for localized delivery of anticancer drugs and chemosensitizers. Because of their hydrophilic nature, the IE-MS release their payload quickly. The purpose of this work was to develop an IE-MS system that could provide a broad range of releas...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Liu Z,Wu XY,Ballinger JR,Bendayan R

    更新日期:2000-06-01 00:00:00

  • Binder-Jet 3D Printing of Indomethacin-laden Pharmaceutical Dosage Forms.

    abstract::Emerging 3D printing technologies offer an exciting opportunity to create customized 3D objects additively from a digital design file. 3D printing may be further leveraged for personalized medicine, clinical trial, and controlled release applications. A wide variety of 3D printing methods exists, and many studies focu...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chang SY,Li SW,Kowsari K,Shetty A,Sorrells L,Sen K,Nagapudi K,Chaudhuri B,Ma AWK

    更新日期:2020-10-01 00:00:00

  • In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing.

    abstract::Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in rela...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Teo SY,Yew MY,Lee SY,Rathbone MJ,Gan SN,Coombes AGA

    更新日期:2017-01-01 00:00:00

  • Effect of low molecular weight chitosans on drug permeation through mouse skin: 1. Transdermal delivery of baicalin.

    abstract::The aim of this work was to evaluate the low molecular weight chitosans (LMWCs) as enhancers of transdermal administration of baicalin, an useful drug for the treatment of atopic dermatitis, viral hepatitis, and HIV infection. Permeation experiments were performed in vitro through mouse skin by using Franz cells. Impr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Zhou X,Liu D,Liu H,Yang Q,Yao K,Wang X,Wang L,Yang X

    更新日期:2010-07-01 00:00:00

  • Protein transduction domain-containing microemulsions as cutaneous delivery systems for an anticancer agent.

    abstract::In this study, we developed cationic microemulsions containing a protein transduction domain (penetratin) for optimizing paclitaxel localization within the skin. Microemulsions were prepared by mixing a surfactant blend (BRIJ:ethanol:propylene glycol 2:1:1, w/w/w) with monocaprylin (oil phase) at 1.3:1 ratio, and addi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Pepe D,McCall M,Zheng H,Lopes LB

    更新日期:2013-05-01 00:00:00

  • Feasibility of atomic force microscopy for determining crystal growth rates of nifedipine at the surface of amorphous solids with and without polymers.

    abstract::Amorphous nifedipine (NFD), which has a smooth surface immediately after preparation, was shown to have structures resembling clusters of curling and branching fibers approximately 1 μm wide by atomic force microscopy (AFM) after storage at 25°C. The size of the cluster-like structures increased with storage over time...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Miyazaki T,Aso Y,Kawanishi T

    更新日期:2011-10-01 00:00:00

  • Technical decision-making with higher order structure data: specific binding of a nonionic detergent perturbs higher order structure of a therapeutic monoclonal antibody.

    abstract::Robust higher order structure (HOS) characterization capability and strategy are critical throughout biopharmaceutical development from initial candidate selection and formulation screening to process optimization and manufacturing. This case study describes the utility of several orthogonal HOS methods as investigati...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Budyak IL,Doyle BL,Weiss WF 4th

    更新日期:2015-04-01 00:00:00

  • Characterization of site I of human serum albumin using spectroscopic analyses: locational relations between regions Ib and Ic of site I.

    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

    pub_type: 杂志文章


    authors: Yamasaki K,Maruyama T,Takadate A,Suenaga A,Kragh-Hansen U,Otagiri M

    更新日期:2004-12-01 00:00:00

  • Differential elimination of synthetic butyric triglycerides in vivo: a pharmacokinetic study.

    abstract::New butyrate derivatives were synthesized to investigate the residence time of potent butyric acid in vivo. These derivatives were triglycerides in which one, two, or three butyric acid molecules were bound to glycerol or to mono- and dipalmitic esters of glycerol. Pharmacokinetic studies showed that a constant plasma...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Planchon P,Pouillart P,Ronco G,Villa P,Pieri F

    更新日期:1993-10-01 00:00:00

  • Transport Mechanism of Nicotine in Primary Cultured Alveolar Epithelial Cells.

    abstract::Nicotine is absorbed from the lungs into the systemic circulation during cigarette smoking. However, there is little information concerning the transport mechanism of nicotine in alveolar epithelial cells. In this study, we characterized the uptake of nicotine in rat primary cultured type II (TII) and transdifferentia...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Takano M,Nagahiro M,Yumoto R

    更新日期:2016-02-01 00:00:00

  • Control systems engineering in continuous pharmaceutical manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

    abstract::This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审


    authors: Myerson AS,Krumme M,Nasr M,Thomas H,Braatz RD

    更新日期:2015-03-01 00:00:00

  • High-performance liquid chromatographic determination of 4-amino-5-chloro-N-[(1-ethylimidazolin-2-yl)methyl]-2-methoxybenzamide and its metabolite in biological fluids. Applications in pharmacokinetic studies.

    abstract::A high-performance liquid chromatographic method with spectrofluorometric detection has been developed for the analysis of a new substituted benzamide and its metabolite in body fluids. The detection was performed at 270 nm for excitation, and 370 nm for emission. The proposed technique is selective, reliable, and sen...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Bressolle F,Bres J,Moulin A

    更新日期:1990-06-01 00:00:00

  • Swelling and polymer erosion for poly(ethylene oxide) tablets of different molecular weights polydispersities.

    abstract::The aim of the study was to determine and compare the degree of swelling and the swelling kinetics of poly(ethylene oxide) (PEO) hydrophilic matrix tablets without any additives for matrixes with different molecular weight polydispersities. A wide range of "mixed" polydisperse PEO tablets were obtained by mixing two P...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Körner A,Larsson A,Andersson A,Piculell L

    更新日期:2010-03-01 00:00:00

  • Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel.

    abstract::The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free a...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Zhang Q,Song Y,Page SW,Garg S

    更新日期:2018-02-01 00:00:00

  • Time-dependent changes in the activation of RhoA/ROCK and ERM/p-ERM in the increased expression of intestinal P-glycoprotein by repeated oral treatment with etoposide.

    abstract::Previously, we reported that repeated oral treatment with etoposide (ETP) increased ileal membrane localization of P-glycoprotein (P-gp) and that this was possibly mediated by increased expression of the ezrin/radixin/moesin (ERM)/phosphorylated ERM (p-ERM) via activation of RhoA/ROCK. These changes caused decreases i...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kobori T,Harada S,Nakamoto K,Tokuyama S

    更新日期:2013-05-01 00:00:00

  • A double Weibull input function describes the complex absorption of sustained-release oral sodium valproate.

    abstract::The pharmacokinetics of valproic acid after oral administration of sustained-release formulations were studied in 12 healthy volunteers. The objective of the present study was to find an appropriate mathematical model to describe the complex drug intake process. The concentration of valproic acid in plasma was measure...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Bressolle F,Gomeni R,Alric R,Royer-Morrot MJ,Necciari J

    更新日期:1994-10-01 00:00:00

  • STRITERFIT, a least-squares pharmacokinetic curve-fitting package using a programmable calculator.

    abstract::A program is described that permits iterative least-squares nonlinear regression fitting of polyexponential curves using the Hewlett Packard HP 41 CV programmable calculator. The program enables the analysis of pharmacokinetic drug level profiles with a high degree of precision. Up to 15 data pairs can be used, and in...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Thornhill DP,Schwerzel E

    更新日期:1985-05-01 00:00:00

  • Mechanistic study of alkyl azacycloheptanones as skin permeation enhancers by permeation and partition experiments with hairless mouse skin.

    abstract::In previous studies (Yoneto et al., 1995. J Pharm Sci 84:312-317; Kim et al., 1992. Int J Pharm 80:17-31; and Warner et al., 2001. J Pharm Sci 90:1143-53), the transport enhancing effects of four homologous series of enhancers-the n-alkanols, 1-alkyl-2-pyrrolidones, 1,2-alkanediols, and N,N-dimethylalkanamides - on th...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: He N,Li SK,Suhonen TM,Warner KS,Higuchi WI

    更新日期:2003-02-01 00:00:00

  • Impurities in a morphine sulfate drug product identified as 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine.

    abstract::Stability testing of morphine sulfate formulated with nonpareil sugar seeds (consisting of sucrose and starch) and fumaric acid revealed the formation of the three impurities 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine. 5-(Hydroxymethyl)-2-furfural was isolated via semipreparative HPLC utilizin...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kelly SS,Glynn PM,Madden SJ,Grayson DH

    更新日期:2003-03-01 00:00:00

  • Stability of apomorphine in solutions containing ascorbic acid and bisulfite and effects of antioxidants on apomorphine-induced cage climbing and hypothermia in mice.

    abstract::Ascorbic acid (100 mg/ml) and sodium bisulfite (0.5 and 20 mg/ml) prevented more than 10% oxidation of apomorphine hydrochloride in water maintained at room temperature over 1-3 days. Refrigeration at 5 degrees prevented oxidation of apomorphine hydrochloride in aqueous solutions for 1 week. Neither ascorbic acid nor ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wilcox RE,Humphrey DW,Riffee WH,Smith RV

    更新日期:1980-08-01 00:00:00

  • The Impact of Sonication on the Surface Quality of Single-Walled Carbon Nanotubes.

    abstract::Sonication process is regularly adopted for dispersing single-walled carbon nanotubes (SWCNTs) in an aqueous medium. This can be achieved by either covalent functionalization of SWCNTs with strong acid or by noncovalent functionalization using dispersants that adsorb onto the surface of SWCNTs during dispersion. Becau...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Koh B,Cheng W

    更新日期:2015-08-01 00:00:00

  • Identification of Endogenous Biomarkers to Predict the Propensity of Drug Candidates to Cause Hepatic or Renal Transporter-Mediated Drug-Drug Interactions.

    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


    authors: Chu X,Chan GH,Evers R

    更新日期:2017-09-01 00:00:00

  • Characterization of a Stable 2,2'-Azobis(2-Methylpropanenitrile) Degradant and Its Use to Monitor the Oxidative Environment During Forced Degradation Studies by Liquid Chromatography/Mass Spectrometry.

    abstract::Azo compounds are commonly used to study radical-mediated degradation of pharmaceutical compounds. The favorable chemical and physical properties of 2,2'-azobis(2-methylpropanenitrile) (AIBN) have made it one of the most widely used compound for these type of studies. This article describes the characterization of a s...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wells-Knecht KJ,Dunn D

    更新日期:2019-09-01 00:00:00

  • Reduced hydrolytic lability of epoprostenol in the presence of cationic micelles.

    abstract::The rapid hydrolysis of epoprostenol to 6-keto-prostaglandin F1 alpha is hydronium ion-catalyzed even at pH 10 or higher. In the presence of 1.0% hexadecyltrimethylammonium chloride, the rate was reduced significantly (1580-fold at pH 2 and 283-fold at a physiological pH). This decrease in the hydrolysis rate is attri...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Cho MJ

    更新日期:1982-04-01 00:00:00

  • Comprehensive high-performance liquid chromatographic methodology for the determination of thiothixene in bulk drug, finished product, and dissolution testing samples.

    abstract::An HPLC methodology is described which enables the quantitation of thiothixene (N,N-dimethyl-9-[3-(4-methyl-1-piperazinyl)-propylidene]thioxanthe ne-2- sulfonamide) in bulk drug, finished product, and dissolution samples using a single analytical column (SiAl: a mixture of silica and alumina). The Z (cis) and the less...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Severin G

    更新日期:1987-03-01 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

  • Prediction of granule packing and flow behavior based on particle size and shape analysis.

    abstract::Packing behavior and flowability of particulate material have long been acknowledged as important parameters for the processing of pharmaceutical materials. When properly understood, these properties can provide insight into weight uniformity, tableting performance and process design. The aim of this study was to meas...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Sandler N,Wilson D

    更新日期:2010-02-01 00:00:00

  • Polymorphism and solvatomorphism 2007.

    abstract::Papers and patents that deal with polymorphism (crystal systems for which a substance can exist in structures characterized by different unit cells, but where each of the forms has exactly the same elemental composition) and solvatomorphism (systems where the crystal structures of the substance are defined by differen...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审


    authors: Brittain HG

    更新日期:2009-05-01 00:00:00

  • Disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate, a potent 5-hydroxytryptamine antagonist, and two metabolites in dogs and monkeys.

    abstract::The disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222; 1), a potent 5-hydroxytryptamine antagonist, and its N-demethylated and N-oxide metabolites was studied in dogs and monkeys. After single, intravenous doses of 1 at 5 mg/kg, the mean terminal half-lives of 1 in plasma were 2.6 ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Cheng H,Larsen DL,Ragner JA,Sproles GD,Gordon WP

    更新日期:1992-04-01 00:00:00