Abstract:
:Corneal penetration studies were conducted in unanesthetized albino rabbits using various organic compounds representing both polar and nonpolar species. Very low molecular weight compounds demonstrate rapid uptake into the aqueous humor despite the lipid-like barrier imposed by the corneal epithelium. Evidence that these compounds may have access to a diffusional channel for corneal transport is presented. In vitro permeability studies were also conducted in an effort to quantitate the corneal diffusion of compounds covering a range of molecular weights and partition coefficients; the results corresponded well with the results of in vivo experiments. Calculations of energies of activation, taken from Arrhenius plots, indicate that the diffusion of drug across the cornea may be by two different mechanisms that depend on the physical-chemical characteristics of the perfusant. One mechanism appears similar to drug movement in an aqueous environment and is characterized by an activation energy similar to that for diffusion in water. The other relates to the expected partitioning of a compound across cellular membranes represented by a relatively high activation energy for diffusion. For hyrdophilic compounds, the epithelium appears to be rate limiting to drug movement, whereas for hydrophobic compounds, the stroma is rate limiting. In the presence of calcium-chelating agents, glycerol demonstrated an increase in corneal penetration in vivo. This effect appears to be reversible at specific concentrations of chelator. In contrast, divalent cations reduced corneal penetration of glycerol. The known calcium chelator EDTA was shown to penetrate the cornea, conjunctiva, and iris/ciliary body from a topically applied dose. The implications of this observation pertain to toxicity effects when EDTA is incorporated into ocular drug products for stability purposes, or novel stratagems for improving ocular bioavailability of topically applied drugs are employed. The addition of calcium-chelating agents to in vivo mounted corneas demonstrated increases in permeability of the cornea to glycerol which were directly related to the concentration of chelating agent used. These results paralleled the findings of similar in vivo studies. The results of these studies are consistent with a currently proposed 'pore' model for the penetration of drugs through the cornea which demonstrates both a partition coefficient and molecular weight dependency on the permeability of the cornea to transported compounds.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Grass GM,Robinson JRdoi
10.1002/jps.2600770103subject
Has Abstractpub_date
1988-01-01 00:00:00pages
3-14issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(15)47605-1journal_volume
77pub_type
杂志文章abstract::Many pathophysiological circumstances vary during 24 h periods. Many physiologic processes undergo biological rhythms, including the sleep-wake rhythm and metabolism. Disruptive effect in the 24 h variations can manifest as the emergence or exacerbation of pathological conditions. So, chronotherapeutics is gaining inc...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.22656
更新日期:2011-09-01 00:00:00
abstract::The intrinsic factor-mediated binding of cyanocobalamin to cholestyramine was studied in vitro under varying conditions of pH, added electrolyte, and bile salt. The intrinsic factor-cyanocobalamin complex was adsorbed strongly by the resin at pH 3 in the presence of neutral salt and low concentrations of glycocholic a...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600671132
更新日期:1978-11-01 00:00:00
abstract::There is a growing clinical interest in developing and commercializing pharmaceutical-grade cannabinoid products, containing primarily tetrahydrocannabinol (THC) and cannabidiol (CBD). The oral bioavailability of THC and CBD is very low due to extensive "first-pass" metabolism. A novel oral THC and CBD formulation, PT...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2017.12.020
更新日期:2018-05-01 00:00:00
abstract::The aminoxyl (nitroxyl) labeled (2-chloroethyl)nitrosocarbamoyl (CNC) derivatives of amino acids, i.e., N-[[N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl]-A-(1-oxy-2,2,6,6- tetramethylpiperidin-4-yl)amides, A = glycyl (10a), A = L-alanyl (10b), A = L-valyl (10c), A = L-phenylalanyl (10d), were synthesized and evaluated ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600830715
更新日期:1994-07-01 00:00:00
abstract::For development and optimization of protein formulation sensitive analytical tools are required to follow both aggregation and changes in protein structure. The latter can be seen as the beginning of physical instability leading to aggregation. The focus of this work laid on the development of a novel analysis simulta...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22808
更新日期:2012-02-01 00:00:00
abstract::Prostaglandin F2 alpha was administered intraamniotically to 132 mid-first trimester gravidas to determine the dose-24-hour abortifacient response relationship. Single doses between 15-50 mg and multiple doses between 15-25 mg were administered to 3 groups each, the latter regimen at 6-hour intervals. Trials were de...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600620809
更新日期:1973-08-01 00:00:00
abstract::The O-trifluoroacetyl and N,O-trifluoroacetyl derivatives of a series of aporphine and noraporphine alkaloids were prepared, and their GLC and mass spectrometric characteristics were determined. The positional isomers apocodeine and isoapocodeine were resolved chromatographically as their trifluoroacetyl derivatives, ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600690819
更新日期:1980-08-01 00:00:00
abstract::Citric acid anhydrate (CAA) and paracetamol (PARA), prepared as crystalline physical mixtures and as amorphous blends, were studied using (13)C solid-state cross polarization magic angle spinning (CPMAS) NMR. Amorphous blends showed significant line broadening from the conformational distribution as compared to the cr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21559
更新日期:2009-05-01 00:00:00
abstract::A GLC determination of cyclobenzaprine in human plasma and urine is described. After extraction from alkalinized samples with heptane-isopentyl alcohol (97:3), the drug and internal standard were back-extracted into 0.1 N HCl and then reextracted into ether. Use of a lower homolog of the drug as an internal standard w...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650832
更新日期:1976-08-01 00:00:00
abstract::In this study, we explored the bioavailability in dogs and chemical potency of generic ritonavir and lopinavir/ritonavir tablet products manufactured by various pharmaceutical companies. Chemical potency of the products was examined by HPLC quantitation of ritonavir and lopinavir. Using a dog model, we determined poin...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21712
更新日期:2010-02-01 00:00:00
abstract::Human insulin exists in different association states, from monomer to hexamer, depending on the conditions. In the presence of zinc the "normal" state is a hexamer. The structural properties of 20 variants of human insulin were studied by near-UV circular dichroism, fluorescence spectroscopy, and small-angle X-ray sca...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10355
更新日期:2003-04-01 00:00:00
abstract::The sensitivity of pharmacokinetic deconvolution algorithms with respect to simulated experimental error has been studied. Approximations of cumulative absorption profiles reconstructed from simulated data sets with normally distributed random error were compared with corresponding known input functions. The coinciden...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600781114
更新日期:1989-11-01 00:00:00
abstract::Modified cyclodextrins (CDs) have shown great promise as non-viral gene and siRNA delivery vectors in a range of in vitro and in vivo studies. In the current study, structural and biophysical characterisation of selected CDs was carried out to enhance our understanding of their interaction with nucleic acids. The meth...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23922
更新日期:2014-05-01 00:00:00
abstract::Cisplatin (CDDP) is an effective anticancer agent for many solid tumors but has significant systemic toxicity limiting its use in many patients. We have designed a loco-regional delivery system to increase platinum levels in the lymphatics, where early metastasis is most likely to occur, while reducing systemic toxici...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22016
更新日期:2010-06-01 00:00:00
abstract::Quantitative applications for pharmaceutical solid dosage forms using near-infrared (NIR) spectroscopy are central to process analytical technology (PAT) manufacturing designs. A series of studies were conducted to evaluate the use of NIR transmission mode under various pharmaceutical settings. The spectral variabilit...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21777
更新日期:2009-12-01 00:00:00
abstract::Acitretin, a retinoid for the treatment of severe psoriasis, exhibits extremely low aqueous solubility and high photosensitivity. This study investigated the effects of the complexation of acitretin with the respective hydroxypropyl-beta-cyclodextrin (HPBCD) and randomly substituted methyl-beta-cyclodextrin (RMBCD) on...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10495
更新日期:2003-12-01 00:00:00
abstract::The binding of nine diazepines to human serum albumin (HSA) and to alpha 1-acid glycoprotein (AGP) was investigated by means of fluorescence and circular dichroism (CD) spectroscopies. The binding parameters of diazepam obtained from fluorescence agreed with those obtained from CD measurements. Diazepines have one tig...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600810104
更新日期:1992-01-01 00:00:00
abstract::Pharmacokinetic profiles of pentylenetetrazol in the dog were studied following rapid intravenous and oral administrations of a convulsant dose (15-20 mg/kg). Plasma level-time curves after a rapid intravenous injection showed biexponential decline, indicating that the disposition of this drug in the dog follows a two...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650720
更新日期:1976-07-01 00:00:00
abstract::The adsorption of cimetidine on selected pharmaceuticals including kaolin, activated charcoal, talc, and nonsystemic antacids was determined at pH 5.0 and 25 degrees. The Langmuir and Freundlich adsorption isotherms showed that cimetidine adsorption was significant with activated charcoal, kaolin, talc, and magnesium ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600690329
更新日期:1980-03-01 00:00:00
abstract::Surface adsorption of two monoclonal antibodies (mAb1 and mAb2), with widely different hydrophobicity and self-association behavior in solution, was examined by quartz crystal microbalance with dissipation monitoring to understand how adsorption and protein self-interactions near the surface are impacted by their intr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22771
更新日期:2012-02-01 00:00:00
abstract::The highly lipid soluble, free-base form of halofantrine (Hf base; approximately 50 mg/mL in triglyceride lipids), a highly lipophilic (calculated log P approximately 8.5) antimalarial, has recently been shown to undergo significant intestinal lymphatic transport (54% of administered dose) after postprandial administr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10045
更新日期:2002-03-01 00:00:00
abstract::Bile acid (BA) retention within hepatocytes is an underlying mechanism of cholestatic drug-induced liver injury (DILI). We previously developed an assay using sandwich-cultured human hepatocytes (SCHHs) to evaluate drug-induced hepatocyte toxicity accompanying intracellular BA accumulation. However, due to shortcoming...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.01.013
更新日期:2016-04-01 00:00:00
abstract::The relative sweetness, onset times, and durations of response of D-glucose, D-xylose, D-quinovose, D-galactose, L-arabinose, and D-fucose were determined at four temperatures. The results can be interpreted by simple concepts of intramolecular hydrogen bonding which indicate that the so-called gamma-function of the t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600700313
更新日期:1981-03-01 00:00:00
abstract::Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies w...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1016/j.xphs.2018.03.009
更新日期:2018-07-01 00:00:00
abstract::The rising popularity of microwaves for drying, material processing and quality sensing has fuelled the need for knowledge concerning dielectric properties of common pharmaceutical materials. This article represents one of the few reports on the density and moisture content dependence of the dielectric properties of p...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21872
更新日期:2010-02-01 00:00:00
abstract::The purpose of this study was to examine the role of multidrug resistance-associated protein-1 and -2 (Mrp1 and Mrp2) in the efflux transport of organic anions across the blood-cerebrospinal fluid (CSF) barrier. The CSF concentration of estradiol-17beta-glucuronide (E(2)17betaG) and 2,4-dinitrophenyl-S-glutathione (DN...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10521
更新日期:2004-01-01 00:00:00
abstract::The viscosity and surface tension of systems containing small amounts of salicylic acid in aqueous solutions of cetrimide were determined. An abrupt increase in viscosity was observed, and the molar ratio of salicylic acid to certrimide at which this viscosity increase occurred was 1:2. The surface tension of these sy...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600661236
更新日期:1977-12-01 00:00:00
abstract::Aliphatic polyesters have great utility as temporary prosthetics and surgical aids, and in drug delivery systems. Knowledge of the mechanism and pathways of hydrolysis can form a basis for the design and selection of a controlled-release system. Because of the importance of hydrolysis to the properties of such a syste...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800815
更新日期:1991-08-01 00:00:00
abstract::Methods for the determination of diphenoxylate hydrochloride and atropine sulfate combinations in solutions and powdered tablet composites are presented. A semiautomated assay for diphenoxylate hydrochloride in individual tablets (content uniformity) also is presented. The USP XIX assays for these products are cumbers...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600661113
更新日期:1977-11-01 00:00:00
abstract::After having been used in treating HIV infection for a decade, zidovudine (AZT) continues to be an essential component of antiretroviral regimens. Because antiviral responses and toxicity of AZT seem to be related to cells in specific target tissues, being able to understand and predict the distribution of AZT into di...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js970243y
更新日期:1997-11-01 00:00:00