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Water-insoluble Compounds (water-insoluble + compound)
Selected AbstractsEncapsulation of Water-Insoluble Drugs in Polymer Capsules Prepared Using Mesoporous Silica Templates for Intracellular Drug DeliveryADVANCED MATERIALS, Issue 38 2010Yajun Wang Water-insoluble compounds were encapsulated in polymer capsules through mesoporous silica nanoparticle-mediated layer-by-layer assembly. The drug-loaded capsules exhibit excellent colloidal stability and high potency to colorectal cancer cells in vitro with similar cytotoxicity to the free drug dissolved in organic solvent. [source] Pharmacokinetics and protein binding of the selective neuronal nitric oxide synthase inhibitor 7-nitroindazoleBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2000Mark A. Bush Abstract Utilization of nitric oxide (NO) synthase (NOS) inhibitors to probe the role of NO in various central nervous system processes requires use of an inhibitor selective for neuronal NOS, and is facilitated by knowledge of the pharmacokinetics of the inhibitor. The present project was undertaken to elucidate the disposition of the selective neuronal NOS inhibitor 7-nitroindazole (7-NI). A simple, specific HPLC assay was developed with requisite sensitivity to quantitate 7-NI in serum after administration of pharmacologically relevant doses. Further experiments were performed to assess the effects of administered dose on 7-NI disposition. 7-NI displayed marked nonlinearity, consistent with saturable elimination, when administered by ip injection in peanut oil. The nonlinearity was related to total dose, but not to the concentration of 7-NI in the vehicle. Binding of 7-NI in rat serum was concentration-independent and does not contribute to the nonlinearity. Various formulations for iv administration of this water-insoluble compound were evaluated; the optimal vehicle, from the standpoint of 7-NI solubility, appeared to inhibit the clearance of 7-NI from the systemic circulation. Considering the nonlinear disposition of 7-NI, knowledge of the pharmacokinetics of this inhibitor is requisite to designing administration protocols to achieve the desired magnitude and duration of NOS inhibition. Copyright © 2000 John Wiley & Sons, Ltd. [source] Radiotracer-based method for determining water solubility of highly insoluble compoundsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2006Ketai Wang Abstract Ascertaining the aqueous solubility of compounds is important in the selection of drug candidates. We describe a radiotracer method for estimating water solubility of compounds that are soluble in dimethyl sulfoxide (DMSO). Various volumes of DMSO, saturated with 127I-labeled compound and spiked with the corresponding 125I-labeled derivative, are mixed in de-ionized water and the tubes centrifuged to remove insoluble material. Since (i) the iodine-127 and iodine-125 compounds have the same solubilities and are equally distributed in the DMSO,water solution, and (ii) the nonradioactive compound is accurately weighed, dissolved in a known volume of DMSO, and then further diluted as required, the concentration of compound in solution can be calculated and plotted as a function of the DMSO-to-water ratio. Water solubility of the compound is then determined by extrapolation of the linear fit of data points to zero DMSO. As proof of the methodology, 5-iodo-2,-deoxyuridine (IUdR) and 2-iodo-8-methyl-8H -quino[4,3,2- kl]acridine (IMAc), water-soluble compounds, were assessed using 125IUdR and 125IMAc, respectively. The solubility values obtained by the radiotracer method were similar to those acquired by spectrophotometry. Values calculated for several water-insoluble compounds indicate that the radiotracer method can accurately quantify the solubility of low-molecular-weight compounds (1000,2000 Da) in the pg,ng/ml range. Copyright © 2006 John Wiley & Sons, Ltd. [source] Evaluation of hydrate-screening methodsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2008Yong Cui Abstract The purpose of this work is to evaluate the effectiveness and reliability of several common hydrate-screening techniques, and to provide guidelines for designing hydrate-screening programs for new drug candidates. Ten hydrate-forming compounds were selected as model compounds and six hydrate-screening approaches were applied to these compounds in an effort to generate their hydrate forms. The results prove that no screening approach is universally effective in finding hydrates for small organic compounds. Rather, a combination of different methods should be used to improve screening reliability. Among the approaches tested, the dynamic water vapor sorption/desorption isotherm (DVI) method and storage under high humidity (HH) yielded 60,70% success ratios, the lowest among all techniques studied. The risk of false negatives arises in particular for nonhygroscopic compounds. On the other hand, both slurry in water (Slurry) and temperature cycling of aqueous suspension (TCS) showed high success rates (90%) with some exceptions. The mixed solvent systems (MSS) procedure also achieved high success rates (90%), and was found to be more suitable for water-insoluble compounds. For water-soluble compounds, MSS may not be the best approach because recrystallization is difficult in solutions with high water activity. Finally, vapor diffusion (VD) yielded a reasonably high success ratio in finding hydrates (80%). However, this method suffers from experimental difficulty and unreliable results for either highly water-soluble or water-insoluble compounds. This study indicates that a reliable hydrate-screening strategy should take into consideration the solubility and hygroscopicity of the compounds studied. A combination of the Slurry or TCS method with the MSS procedure could provide a screening strategy with reasonable reliability. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2730,2744, 2008 [source] | ||||||||||