The Thermal Degradation of Alkaline Earth Metal Salts of Poly(Itaconic Acid)

The Mg-, Ca- and Ba-salts of poly(itaconic acid) (PIA) were prepared by treating the aqueous solution of the polyacid with the corresponding metal oxide or hydroxide. The resulting polysalts were analysed by FTIR spectroscopy and thermogravimetry. The results indicate that the polysalts are thermally more stable than the parent PIA, they all degrade in a similar manner, the Ba-salt being the most stable. This revised version was published online in August 2006 with corrections to the Cover Date.     

Quantitative determination of itazigrel in rodent diet by reversed-phase HPLC and evaluation of its stability at 20 degrees C

A simple, accurate and precise procedure for the quantitation of itazigrel (a potent lipophilic inhibitor of collagen and arachidonic acid-induced aggregation being studied for its effects on peripheral vascular disease) from granulated rodent diet is presented. The drug was extracted from rodent diet using methanol + water (80:20) following dissolution of the diet in water. Samples of the supernatant were injected into the HPLC and the eluent was monitored with a fluorescent detector (lambda ex = 320 and lambda em = 430) to achieve analytical specificity. Interday coefficients of variation of the calibration curve slope were +/- 6% on standards between 0 and 1000 micrograms/g. Potency and homogeneity of the drug spiked diet prepared over a 1 year interval at 70, 200 and 600 micrograms/g was 99.3 +/- 2.5%, 100 +/- 1.8%, and 101 +/- 1.9% of label, respectively. Samples prepared for chromatography were stable for 24 h at 20 degrees C, and drug in diet was stable for 102 days when protected from light and stored at 20 degrees C.     

The thermal degradation of some alkali metal salts of poly(itaconic acid)

The Li-, Na- and K salts of poly(itaconic acid) (PIA) were prepared by treating the polyacid with the corresponding aqueous hydroxide.The resulting polysalts were analyzed by elemental analysis, FTIR spectroscopy and thermogravimetry. The results indicate that the polysalts are thermally more stable than the parent PIA, they all degrade in a similar manner and somewhat more complexly than the poly(methacrylic acid) salts.     

A ceric ammonium nitrate N-dearylation of N-p-anisylazoles applied to pyrazole, triazole, tetrazole, and pentazole rings: release of parent azoles. generation of unstable pentazole, HN5/N5-, in solution

The reaction of cerium(IV) ammonium nitrate (CAN) with a range of N-(p-anisyl)azoles in acetonitrile or methanol solvents leads to N-dearylation releasing the parent NH-azole and p-benzoquinone in comparable yields. The scope and limitations of the reaction are explored. It was successful with 1-(p-anisyl)pyrazoles, 2-(p-anisyl)-1,2,3-triazoles, 2-(p-anisyl)-2H-tetrazoles, and 1-(p-anisyl)pentazole. The dearylation renders the p-anisyl group as a potentially useful N-protecting group in azole chemistry. The azole released in solution from 1-(p-anisyl)pentazole is unstable HN5, the long-sought parent pentazolic acid. p-Anisylpentazole samples were synthesized with combinations of one, two, and three 15N atoms at all positions of the pentazole ring. The unstable HN5/N5- produced at -40 degrees C did not build up in the solution but degraded to azide ion and nitrogen gas with a short lifetime. The 15N-labeling of the N3- ion obtained from all samples proved unequivocally that it came from the degradation of HN5 (tautomeric forms) and/or its anion N5- in the solution.     

Structural changes of polyacids initiated by their neutralization with various alkali metal hydroxides. Diffusion studies in poly(acrylic acid)s

The changes in the three-dimensional structure of the poly(acrylic acid), PAA, induced by incorporation of various alkali-metal counterions have been evaluated by studying diffusion of an uncharged probe (1,1'-ferrocenedimethanol) in the polymeric media. The studies are supported by the measurements of conductivity and viscosity of the polymeric media. Solutions of linear PAA of four different sizes (molecular weights: 450,000, 750,000, 1,250,000, 4,000,000) were neutralized with hydroxides of alkali metals of group 1 of the periodic table (Li, Na, K, Rb, Cs) to the desired neutralization degree. The transport properties of the obtained polyacrylates were monitored by measuring the changes in the probe diffusion coefficient during the titration of the polyacids. The probe diffusivity was determined from the steady-state current of the probe voltammetric oxidation at disk microelectrodes. Diffusivity of the probe increases with the increase in the degree of neutralization and with the increase in viscosity. It reaches the maximum value at about 60-80% of the polyacid neutralization. The way the probe diffusion coefficients change is similar in all polyacid solutions and gels. The increase in the size of a metal cation causes, in general, an enhancement in the transport of probe molecules. The biggest differences in the probe diffusivities are between lithium and cesium polyacrylates. The differences between the results obtained for cesium and rubidium are not statistically significant due to lack of good precision of the voltammetric measurements. The measurements of the electric conductivity of polyacrylates and the theoretical predictions supplemented the picture of electrostatic interactions between the polyanionic chains and the metal cations of increasing size. In all instances of the PAAs, the viscosity of the solutions rapidly increases in the 0-60% range of neutralization and then becomes constant in the 60-100% region. With the exception of the shortest chain polyacid, the formation of a rigid medium (gel) has been observed in the experiments with all cations. After the end point of the titration was passed, a sudden drop in the viscosity and the disappearance of the gelatinous structure were seen. The largest value of viscosity has been recorded for the longest chain polyacid. The change in the cation of the strong base used did not affect the viscosity of the polymeric system.     

Synthesis and characterization of novel polyacid-stabilized latexes

A series of novel polyacid macromonomers based on 2-hydroxypropyl methacrylate (HPMA) were prepared by atom transfer radical polymerization (ATRP) via a two-step route. First, a range of well-defined PHPMA homopolymer precursors were synthesized by ATRP using a tertiary amine-functionalized initiator, 2-(dimethylamino)ethyl-2-bromoisobutyrylamide, and a CuCl/2, 2'-bipyridine (bpy) catalyst in alcoholic media at 50 °C. ATRP polymerizations were relatively slow and poorly controlled in pure isopropanol (IPA), especially when targeting higher degrees of polymerization (DP > 30). Improved control was achieved by addition of water: low polydispersity (M(w)/M(n) < 1.25) PHPMA homopolymers of DP = 30, 40, 50, 60, or 70 were successfully prepared using a 9:1 w/w % IPA/water mixture at 50 °C. These PHPMA homopolymer precursors were then derivatized to produce the corresponding poly(2-(succinyloxy)propyl methacrylate) (PSPMA) macromonomers by quaternizing the tertiary amine end-group with excess 4-vinylbenzyl chloride, followed by esterification of the pendent hydroxyl groups using excess succinic anhydride at 20 °C. These polyacid macromonomers were evaluated as reactive steric stabilizers for polystyrene latex synthesis under either aqueous emulsion polymerization or alcoholic dispersion polymerization conditions. Near-monodisperse polystyrene latexes were obtained via aqueous emulsion polymerization using 10 wt % PSPMA macromonomer (with respect to styrene monomer) with various initiators as evidenced by scanning electron microscopy, disk centrifuge photosedimentometry and light scattering studies. PSPMA macromomer concentrations as low as 1.0 wt % also produced near-monodisperse latexes, suggesting that these PSPMA macromonomers are highly effective stabilizers. Alcoholic dispersion polymerization of styrene conducted in various ethanol/water mixtures with 10 wt % PSPMA(50) macromonomer produced relatively large near-monodisperse latexes. Increasing the water content in such formulations led to smaller latexes, as expected. Control experiments conducted with 10 wt % PSPMA(50) homopolymer produced relatively large polydisperse latexes via emulsion polymerization and only macroscopic precipitates via alcoholic dispersion polymerization. Thus the terminal styrene group on the macromonomer chains is essential for the formation of well-defined latexes. FT-IR spectroscopy indicated that these latexes contained PSPMA macromonomer, whereas (1)H NMR spectroscopy studies of dissolved latexes allowed stabilizer contents to be determined. Aqueous electrophoresis and X-ray photoelectron spectroscopy studies confirmed that the PSPMA macromonomer chains were located at the latex surface, as expected. Finally, these polyacid-stabilized polystyrene latexes exhibited excellent freeze-thaw stability and remained colloidally stable in the presence of electrolyte.     

A simple, rapid and sensitive method for simultaneous determination of rivastigmine and its major metabolite NAP 226-90 in rat brain and plasma by reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry

A simple and sensitive reversed-phase liquid chromatography coupled with electrospray-mass spectrometry was developed and validated for the simultaneous determination of rivastigmine, a cholinesterase inhibitor, and its major metabolite NAP 226-90 in rat plasma and brain homogenates. Rivastigmine and NAP 226-90 were extracted from plasma and brain by ethyl acetate and, after drying under nitrogen, re-dissolved in acetonitrile and separated isocratic by HPLC on a C(18) column and quantified by single ion monitoring mass spectrometer. The mean (+/-SD) extraction efficiency for rivastigmine in plasma and brain was 93 +/- 2 and 95 +/- 2% (n = 5) of NAP 226-90 in a drug range of 10-100 pmol/mL or pmol/g. The method proved to be linear within the tested range (regression coefficient, r = 0.9999, n = 5). Intra- and inter-day precision coefficients of variation and accuracy bias were acceptable (within 15%, n = 5) over the entire range for both compounds using plasma or brain samples. The limits of quantification were 0.5 pmol/mL plasma and 2.5 pmol/g brain for rivastigmine and 1 pmol/mL plasma and 5 pmol/g brain for NAP 226-90, respectively. The analytical technique was used to determine the concentrations of rivastigmine and its metabolite NAP 226-90 in rat plasma and brain after oral drug administration. The concentrations of the parent drug and its major metabolite were compared to a pharmacodynamic parameter, the ex vivo inhibition of acetylcholinesterase.     

Flow injection analysis with tubular membrane ion-selective electrode and coated wires for buspirone hydrochloride

New Plastic membrane ion-selective electrode for buspirone hydrochloride based on buspironium tetraphenylborate was prepared. The electrode exhibited mean slope of calibration graph of 58.4 mV per decade of BusCl concentration at 25 degrees C. The electrode can be used within the concentration range 6.3 x 10(-5) - 10(-2) M BusCl at a pH range of 2.5-7.0. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal temperature coefficient of the electrode, amounting to 0.00056 V degrees C(-1). The electrode showed a very good selectivity for BusCl with respect to a number of inorganic cations, sugars and amino acids. The electrode was applied to the potentiometric determination of the buspirone ion and its pharmaceutical preparation under batch and flow injection conditions. Also, buspirone was determined by conductimetric titrations. Graphite rod, copper and silver coated wire electrodes were prepared and characterized as sensors for the drug under investigation.     

高效液相色谱法测定吲哚美辛控释胶囊的血药浓度和生物利用度

采用ＯＤＳ柱,甲醇－稀磷酸溶液（７６２４）为流动相,２６０ｎｍ为检测波长,建立了测定血浆中吲哚美辛浓度的高效液相色谱法,并测定了吲哚美辛控释胶囊炎痛康的血药浓度。结果表明,血浆中吲哚美辛浓度在０．１２５～５．０ｍｇ／Ｌ范围内线性关系良好（ｒ＝０．９９９６）,检测限６２．５μｇ／Ｌ（Ｓ／Ｎ＝３１）,平均回收率为１００．４％,日内和日间ＲＳＤ均小于５％。１１位受试者单剂量口服炎痛康后的相对生物利用度为１０２．３８％。     

The interactions of tooth colored dental restorative materials with aqueous lactic acid

In this study, the interaction of packable composite and ormocer with aqueous lactic acid solutions were determined and changes compared with those for a polyacid modified resin composite and a glass ionomer. For each material, namely Solitaire, Z‐100, Definite, Dyract AP and Vitremer, eight cylindrical specimens of 6 mm diameter and 12 mm height were prepared and weighed. They were stored individually in 20 cm³ 0.02 mol^?1 lactic acid solution for 1 week, then the pH was determined and the specimens reweighed. This was repeated at 1 week intervals until the specimens were 6 weeks old. The results of this study showed that; polyacid modified resin composites and resin‐modified glass‐ionomers were capable of increasing the pH of lactic acid solutions. The same groups showed an increase in mass during the first week. Composite resins and ormocer showed less increase in mass than the others. Copyright © 2003 John Wiley & Sons, Ltd.     

Study the electrical conductivity of crosslinked polyester doped with different metal salts

Three crosslinked polymers were prepared via condensation polymerization between triethanolamine and glycerol [(25:75%), (50:50%) and (0:100%) (G:TEA)] with maleic anhydride which produced polymers I, II and III consequently. All the prepared polymers were doped with metal salts (CuCl₂, NiCl₂ and FeCl₂). D.C. conductivity was measured in the temperature range of (298–373 K), the result showed that the electrical conductivity increased several orders of magnitude with increasing temperature, the activation energy decreased with increasing conductivity. A.C. measurement is used to calculate the dielectric constant for the polymers in both pure and doped state.     

Hydrolysis behavior of prednisolone 21-hemisuccinate/beta-cyclodextrin amide conjugate: involvement of intramolecular catalysis of amide group in drug release

Prednisolone 21-hemisuccinate/beta-cyclodextrin (beta-CyD) amide conjugate was prepared by binding prednisolone 21-hemisuccinate covalently to the amino group of mono(6-deoxy-6-amino)-beta-CyD through amide linkage. Prednisolone 21-hemisuccinate was intramolecularly transformed to prednisolone 17-hemisuccinate, and the parent drug, prednisolone, was slowly released from the 21-hemisuccinate with a half life of 69 h in pH 7.0 at 37 degrees C; the drug release at 25 degrees C was less than 10% for 48 h. In sharp contrast, the hydrolysis of prednisolone 21-hemisuccinate/beta-CyD amide conjugate was significantly faster (half life of 6.50 min at 25 degrees C) and gave prednisolone and mono(6-deoxy-6-succimino)-beta-CyD as products. The hydrolysis of the beta-CyD amide conjugate was subject to a specific-base catalysis in the alkaline region. The rapid hydrolysis of the conjugate can be ascribed to the involvement of an intramolecular nucleophilic catalysis of the amide group in the reaction. The succinic acid, bound to a drug through ester linkage at one carboxylic group and bound to a pro-moiety through amide linkage at another carboxylic group, may be useful as a spacer for construction of the immediate release type prodrugs of CyDs.     

Determination of 2'-deoxy-5-iodouridine and its metabolite 5-iodouracil by high-performance liquid chromatography with ultraviolet absorbance detection in human serum.

A new assay is described for 2'-deoxy-5-iodouridine, a drug employed as an antiviral agent by topical application. The parent drug, its systemic metabolite 5-iodouracil and an internal standard (5-iodouridine) were extracted from salted serum by an ethyl acetate partition at pH 6.7, back-extracted in alkalinized water and injected into a reversed-phase column. Potassium phosphate buffer-acetonitrile (95:5, v/v) eluted the analytes at a flow-rate of 1.5 ml/min. Detection was at 290 nm. The method proved to be linear in the 100-2000 ng/ml range.     

Preparation and characteristics of nanostructured lipid carriers for control-releasing progesterone by melt-emulsification

Nanostructured lipid carriers (NLC) made from mixtures of solid and spatially incompatible liquid lipids were prepared by melt-emulsification. Their drug loading capacity and releasing properties of progesterone were compared with those of solid lipid nanoparticles (SLN), and the NLC prepared by solvent diffusion method. Monostearin (MS) and stearic acid (SA) were used as solid lipid, whilst the oleic acid (OA) was used as liquid lipid. Properties of carriers such as the particle size and its distribution, drug loading, drug encapsulation efficiency and drug release behavior were investigated. As a result, the drug encapsulation efficiencies were improved by adding the liquid lipid into the solid lipid of nanoparticles. The drug release behavior could be adjusted by the addition of liquid lipid, and the NLC with higher OA content showed the faster rate of drug releasing. NLC had higher efficiency of encapsulation and slower rate of drug release than those of NLC prepared by solvent diffusion method. On the other hand, the NLC with higher drug loading was obtained, though the drug encapsulation efficiency was decreased slightly due to the increase of the amount of drug. The NLC modified with polyethylene glycol (PEG) was also prepared by using polyethylene glycol monostearate (PEG-SA). It was observed that the incorporation of PEG-SA reduced the drug encapsulation efficiency, but increased the rate of drug release. A sample with almost complete drug release in 24 h was obtained by modifying with 1.30 mol% PEG-SA. It indicated that the modified NLC was a potential drug delivery system for oral administration.     

Long-term stability of nutrients in a frozen mixed food control material

A mixed food homogenate was prepared as a quality control material for two multi-center clinical feeding trials. Approximately 100 kg of homogenized human diet material was prepared under controlled conditions to maintain the stability of lipid components. More than 4,800 20-25 g aliquots were prepared and stored at -60 degrees C in glass jars with Teflon-lined lids. The homogeneity of the composite was validated by analysis of moisture and total fat in aliquots taken throughout the dispensing sequence. A portion of the material was reserved at the National Institute of Standards and Technology and further characterized as SRM 1544-Fatty Acids in Diet Composite. Moisture, protein, ash, total lipid, fatty acids, cholesterol, sodium, potassium, calcium, and magnesium were assayed as part of routine quality-control analyses. Components were analyzed over a total time period ranging from 29 months (minerals) to 60 months (moisture), and up to 319 values per nutrient were generated. Results for all components assayed were stable over the time period studied. For example, moisture (n = 319; 60 months) ranged from 70.66 to 72.58 g/100 g with a mean, standard deviation (SD), and relative standard deviation (RSD) of 71.90, 0.27, and 0.4%, respectively. The range, mean, SD, and RSD for cholesterol (mg/100 g; n = 98; 49 months) were 13.54-17.96, 15.14, 0.64, and 4%.     

Determination of alachlor, metolachlor, and their acidic metabolites in soils by microwave-assisted extraction (MAE) combined with solid phase extraction (SPE) coupled with GC-MS and HPLC-UV analysis

A well-validated analytical method based on microwave-assisted extraction (MAE) and SPE is presented for the combined analysis of alachlor, alachlor-oxanilic acid (OXA), alachlor-ethanesulfonic acid (ESA), metolachlor, metolachlor-OXA, metolachlor-ESA residues in soils. Extraction of solutes by soil sample was carried out by MAE for 20 min at 100 degrees C in the presence of 50 mL solution (methanol/water 50:50), the extract was subsequently passed through C18 cartidges and fractionated into two fractions, the first with parent compounds (PCs) analyzed with GC-MS and the second one containing the metabolites analyzed with HPLC. For the SPE step, various types of sorbents (Environmental C18, tC18, Supelclean ENVI-carb, and LiChrolut EN) have been used, and their respective advantages and disadvantages are discussed. After the method optimization, average recovery values of all solutes were > 71% in the 50-500 microg/kg fortification range with RSD <10%. The LOQ and LOD were 10-50 and 5-10 microg/kg, respectively. The method was validated with two types of soils (1 and 2.4% organic matter) and in fresh (12 h aging), intermediate (1 wk aging), and aged (1 month aging) spiked samples. Moreover, residue levels determined after field application of alachlor or metolachlor were higher when soils were processed using this method than with a comparison method based on an overnight flask shaking (FS) of soil suspension.     

Preparation and characteristics of nanostructured lipid carriers for control-releasing progesterone by melt-emulsification

Nanostructured lipid carriers (NLC) made from mixtures of solid and spatially incompatible liquid lipids were prepared by melt-emulsification. Their drug loading capacity and releasing properties of progesterone were compared with those of solid lipid nanoparticles (SLN), and the NLC prepared by solvent diffusion method. Monostearin (MS) and stearic acid (SA) were used as solid lipid, whilst the oleic acid (OA) was used as liquid lipid. Properties of carriers such as the particle size and its distribution, drug loading, drug encapsulation efficiency and drug release behavior were investigated. As a result, the drug encapsulation efficiencies were improved by adding the liquid lipid into the solid lipid of nanoparticles. The drug release behavior could be adjusted by the addition of liquid lipid, and the NLC with higher OA content showed the faster rate of drug releasing. NLC had higher efficiency of encapsulation and slower rate of drug release than those of NLC prepared by solvent diffusion method. On the other hand, the NLC with higher drug loading was obtained, though the drug encapsulation efficiency was decreased slightly due to the increase of the amount of drug. The NLC modified with polyethylene glycol (PEG) was also prepared by using polyethylene glycol monostearate (PEG-SA). It was observed that the incorporation of PEG-SA reduced the drug encapsulation efficiency, but increased the rate of drug release. A sample with almost complete drug release in 24 h was obtained by modifying with 1.30 mol% PEG-SA. It indicated that the modified NLC was a potential drug delivery system for oral administration.     

Study on the conversion of three natural statins from lactone forms to their corresponding hydroxy acid forms and their determination in Pu-Erh tea

Conversions of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, from lactone forms to their corresponding hydroxy acid form in 0.1 N NaOH or 0.05 N KOH (prepared with 25, 50, 75, 90% acetonitrile or methanol in water or 100% water) were evaluated. Results showed that lactone form statins could be transformed almost completely only in alkaline solutions prepared with 25 or 50% acetonitrile. In all methanolic alkaline solutions, lactone form statins could also be converted entirely, nevertheless, they would be further transformed to the methyl ester of the hydroxy acid form and the transformation increased as methanol rises. When lactone and hydroxy acid forms of statins were in methanol, ethyl acetate, 70% acetonitrile in water (with 0.5% acetic acid or no) for 0-48 h at room temperature or in 100 degrees C water for 0-2 h, lactone form statins were converted to their corresponding hydroxy acids, which were raised as time extends and the highest conversions of them were about 35% in 100 degrees C water and 70% acetonitrile, slightly transformed for lactone form statins in 70% acetonitrile (with 0.5% acetic acid) after 8 h, and the other treatments for all statins showed no significant changes. Interferences would be reduced efficiently when statins were extracted from Pu-Erh tea with methanol, ethyl acetate or 100 degrees C water followed by purifying through a C18 solid-phase extraction cartridge. Lovastatin was the only statin found in Pu-Erh tea and the highest content of it was found under ethyl acetate extraction. In ethyl acetate and methanol extracts, lovastatin existed merely as lactone form. The lowest content of lovastatin was found in the 100 degrees C water extract of Pu-Erh tea, however, both of lactone and hydroxy acid forms were found to exist in the extract.     

Formulation studies on a topical gel of tretinoin�Cdimethyl-beta-cyclodextrin complex

The aim of this work was to develop and characterize a 0.05% tretinoin hydrogel formulations in which tretinoin is free or complexed with dimethyl-beta-cyclodextrin in order to compare the main advantages of its complexation. Theoretically, the complexation will mainly allow to: overcome drug low solubility in water and low stability; enhance the drug release by promoting skin absorption and alleviate of drug inducing local irritation. The hydrogels prepared were both microbiological and physically stable during 30 days. However, the chemical stability was less encouraging. The complexed tretinoin gel had also a higher releasing profile than the free tretinoin gel. This study has demonstrated that it is possible to obtain a microbiological and physically stable gel formulation with good releasing profile.