Adjusting timing of weathering test to account for seasonal variations in UV exposure

Satellite-derived UV climatology has been used to design a timetable for the outdoor UV exposure of polymeric material specimens. By pre-exposure computation, fixed time increments are transformed into a schedule with a predicted average accumulation of UV dose. The method was applied to produce a timetable for an ongoing exposure programme in a network of seven European test sites over the latitude range 28.5-67.4°N. The effect of the average seasonal variability of solar UV irradiance on the predicted accumulated UV exposure is shown to be notably diminished by the method. Relative underestimations of 5-82% of cumulative UV stress are estimated to be avoided by extensions of 6-167 days exposure durations as suggested by the adjustment procedure. Hence, more reproducible degradation data are expected to be obtainable for exposures that are not multiples of the full annual cycle of UV, especially for those with a duration <1 year.     

In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations

The main objective of this work was to develop antifungal matrix tablet for vaginal applications using mucoadhesive thiolated polymer. Econazole nitrate (EN) and miconazole nitrate (MN) were used as antifungal drugs to prepare the vaginal tablet formulations. Thiolated poly(acrylic acid)-cysteine (PAA-Cys) conjugate was synthesized by the covalent attachment of L-cysteine to PAA with the formation of amide bonds between the primary amino group of L-cysteine and the carboxylic acid group of the polymer. Vaginal mucoadhesive matrix tablets were prepared by direct compression technique. The investigation focused on the influence of modified polymer on water uptake behavior, mucoadhesive property and release rate of drug. Thiolated polymer increased the water uptake ratio and mucoadhesive property of the formulations. A new simple dissolution technique was developed to simulate the vaginal environment for the evaluation of release behavior of vaginal tablets. In this technique, daily production amount and rate of the vaginal fluid was used without any rotational movement. The drug release was found to be slower from PAA-Cys compared to that from PAA formulations. The similarity study results confirmed that the difference in particle size of EN and MN did not affect their release profile. The release process was described by plotting the fraction released drug versus time and n fitting data to the simple exponential model: M(t)/M(∞)=kt(n). The release kinetics were determined as Super Case II for all the formulations prepared with PAA or PAA-Cys. According to these results the mucoadhesive vaginal tablet formulations prepared with PAA-Cys represent good example for delivery systems which prolong the residence time of drugs at the vaginal mucosal surface.     

A stability indicating assay method for cefuroxime axetil and its application to analysis of tablets exposed to accelerated stability test conditions

Cefuroxime axetil is the esterified form of cefuroxime, injectable second generation cephalosporine antibiotic that can be given orally. Stereo and structural isomers of cefuroxime axetil (CA), anti-cefuroxime axetil (ACA) and Delta(3)-cefuroxime axetil (DCA), can be present in cefuroxime dosage forms as the process related impurities as well as possible degradation product. Sensitive and precise reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination of cefuroxime axetil in the presence of its degradation products in solid dosage forms. The RSD values for cefuroxime axetil, anti-cefuroxime axetil and Delta(3)-cefuroxime axetil of 1.80, 1.99 and 2.48%, respectively, indicated a good precision of the RP-HPLC method. Developed RP-HPLC method was sensitive with LOD = 0.08 microg mL(-1) and LOQ = 0.60 microg mL(-1) for anti-cefuroxime axetil and LOD = 0.06 microg mL(-1) and LOQ = 0.45 microg mL(-1) for Delta(3)-cefuroxime axetil. Holding studies were carried out on Ceroxim tablets, according to ICH regulation at 30 degrees C/60% relative humidity (RH) and 40 degrees C/75% RH for 1, 2, 3 and 6 months. The review data from the stability studies conducted, show the significant content change of Delta(3)-cefuroxime axetil.     

Disintegration of pellets in ocean water

The problem of fixation of water pollutants, e. g., nuclear fission and corrosion products is concerned not only with the chemical and physical properties of these materials but also with the type of their dispersal in open waters under natural turbulent conditions. The delivery of a scavenging system into a required depth was the objective of this study. Pellets disintegrating at such a rate as to deliver the required uniform concentration of reacting chemicals into the contaminated body of water were developed. Attempts were made to depart from an empirical approach and to investigate formation and properties of pellets through systematic studies. Parameters investigated were particle size of pelleted chemicals, pelleting pressure and temperature, and age of pellets. Chemicals used were potassium permanganate; ferrous sulfate, anhydrous and heptahydrate; and ferrous chloride, dihydrate and tetrahydrate. The use of pelleted materials for removal of industrial nuclear waste products from water is feasible under emergency and under normal conditions using pellets designed for the specific conditions.     

Evaluation of the disintegration properties of commercial famotidine 20 mg orally disintegrating tablets using a simple new test and human sensory test

The purpose of this study was to demonstrate the usefulness and broad-applicability of a simple disintegration test method for orally disintegrating tablets (ODT). Eight types of commercial famotidine 20 mg orally disintegrating tablets with different physical properties (formulation, manufacturing method, tablet weight, shape, diameter, thickness, etc.), were used. Disintegration times of these tablets were evaluated employing human sensory test, conventional disintegration test, and the new proposed disintegration test. The human sensory test was performed in 5 healthy volunteers. In the conventional disintegration test, the disintegration apparatus described in the Japanese Pharmacopeia (JP 1(st)) was used. Our proposed new test which is characterized by a rotating shaft with a low weight (10, 15 g) and rotation speed (10, 25, 50 rpm) was evaluated using tablets with and without storage under severe conditions (60 degrees C/75%RH for 1 week). The disintegration times of famotidine 20 mg orally disintegrating tablets in human sensory test varied from 9 to 32 s. In contrast, disintegration times in the conventional test were prolonged to over 300 s. Disintegration times in the new proposed test were close to those in human sensory test. Especially, when the new test was conducted with 15 or 10 g weight and 25 rpm, the slope (human sensory test vs. new proposed test) was almost 1. We were able to demonstrate that the new proposed test was useful to estimate the actual human disintegration time.     

含磷稀土硅化物合金粉化机制的微观研究

采用S300型扫描电子显微镜,对含磷稀土硅化物合金的微观组织结构进行研究,。分析了合金中各物象的形貌特点,合金中各元素特别是P,Ca,Al等杂质元素的面分布规律,研究了合金中微孔 组成与分布,。结果表明：含磷稀土硅化物合金中只有少部分磷化物能够水化,生成氧化物或含磷氧化物,从而对合金粉化起作用,在本实验研究范围内,磷含量不是稀土硅化物合金粉化的决定因素。     

Temperature-triggered self-assembly of ZnO: from nanocrystals to nanorods to tablets

ZnO nanocrystals, nanorods, and tablets were prepared at 110, 140, and 180 degrees C in a water-ethanol system. Nanorods (~2 x 40 nm) arranged in serpentine morphologies formed by the oriented coalescence of anhedral ZnO nanocrystals (~3.5 nm diameter), while tabular ZnO grew by [1210] textural attachment of the nanorods. The development of these crystal habits is believed to proceed via a dissolution and growth mechanism mediated by a transient amorphous phase. Materials synthesized at intermediate temperatures (125 and 160 degrees C) possessed microstructures containing mixed crystal forms in the expected orientation relationship. Photoluminescent spectra of the nanocrystals and nanorods showed blue shifts of 0.16 and 0.13 eV with respect to the bulk ZnO band gap (3.26 eV) due to quantum confinement, with the narrow emission peaks typical of particles possessing uniform size and shape. The larger tablets displayed a less energetic emission (3.10 eV) ascribed to exciton-exciton collisions.     

水解对MCM-41分子筛的结构破坏作用

详细考察了ＳｉＭＣＭ－４１、ＡｌＭＣＭ－４１和ＨＡｌＭＣＭ－４１在不同环境中的水解和结构破坏情况．空气和水蒸汽中短期高温焙烧对全硅型ＳｉＭＣＭ－４１的结构影响较小,但在潮湿空气中长期放置可因Ｓｉ—Ｏ—Ｓｉ键发生水解而造成结构的严重破坏．ＡｌＭＣＭ－４１的抗水解能力优于ＳｉＭＣＭ－４１的,但因其结构中包含一定量的Ｎａ＋离子,降低了高温焙烧时结构的热稳定性和水热稳定性．ＨＡｌＭＣＭ－４１的热稳定性和水热稳定性均优于ＡｌＭＣＭ－４１．分子筛水热晶化过程中的盐析效应被证实是导致ＡｌＭＣＭ－４１和ＨＡｌＭＣＭ－４１抗水解能力增强的原因,因此在合成原料中加盐可显著改善ＭＣＭ－４１分子筛的抗水解能力和稳定性     

Electrospray ionization quadrupole ion-mobility time-of-flight mass spectrometry as a tool to distinguish the lot-to-lot heterogeneity in N-glycosylation profile of the therapeutic monoclonal antibody trastuzumab

Monoclonal antibodies are typically glycosylated at asparagine residues in the Fc domain, and glycosylation heterogeneity at the Fc sites is well known. This paper presents a method for rapid analysis of glycosylation profile of the therapeutic monoclonal antibody trastuzumab from different production batches using electrospray quadrupole ion-mobility time-of-flight mass spectrometry (ESI-Q-IM-TOF). The global glycosylation profile for each production batch was obtained by a fast LC-MS analysis, and comparisons of the glycoprofiles of trastuzumab from different lots were made based on the deconvoluted intact mass spectra. Furthermore, the heterogeneity at each glycosylation site was characterized at the reduced antibody level and at the isolated glycopeptide level. The glycosylation site and glycan structures were confirmed by performing a time-aligned-parallel fragmentation approach using the unique dual-collision cell design of the instrument and the incorporated ion-mobility separation function. Four different production batches of trastuzumab were analyzed and compared in terms of global glycosylation profiles as well as the heterogeneity at each glycosylation site. The results show that each batch of trastuzumab shares the same types of glycoforms but relative abundance of each glycoforms is varied.     

Micro conduction calorimeters to measure enthalpies of vaporization

Details of the construction of micro-conduction calorimeters for measuring enthalpies of vaporization (or sublimation) are described. Accuracy and precision of the calorimeters were tested by the use of a few standard reference compounds. Experimental results showed that the enthalpies of vaporization could be measured for compounds of vapor pressures of 10 Pa to 10 kPa at 298 K with uncertainty less than 0.2 per cent. Results of enthalpy of vaporization measurements for some compounds are also given. Since calorimetric cells of these calorimeters were composed of glass and PTFE, the calorimeters made it possible to measure the enthalpies of vaporization for metal corrosive compounds.     

Disintegration of 1-silalactones under the influence of electron impact

It is shown that the paths of fragmentation of 1-silalactones under the influence of electron impact are determined by the ring size and remain virtually unchanged when the methyl groups attached to the silicon atom are replaced by a chlorine atom or an ethyl group. The possibility of the identification of isomeric silalactones on the basis of their mass spectra was established.     

Attempts to measure sensitiser photophysics in opaque tissue

Diffuse reflectance laser flash photolysis has been used in an attempt to measure transient triplet spectra of the sensitisers, disulphonated aluminium phthalocyanine and porphyrin IX (derived from 5-amino laevulinic acid), in opaque tissue and models. The latter consisted of tissue phantoms; the former included rat liver and red blood cells. In all cases, triplet-triplet absorption spectra with relatively poor signal-to-noise were obtained providing some encouragement in the application of this technique to in vivo studies on photosensitisers.     

How to measure uncertainties in environmental risk assessment

Environmental risk assessment is an essential element in any decision-making process in order to minimize the effects of human activities on the environment. Unfortunately, often environmental data tends to be vague and imprecise, so uncertainty is associated with any study related with these kind of data.

Essentially, uncertainty in risk assessment may have two origins – randomness and incompleteness. There are two main ways to deal with these uncertainties – probability theory and fuzzy logic.

Probability theory is based on a stochastic approach, using probability functions to describe random variability in environmental parameters.

Fuzzy logic uses membership functions and linguistic parameters to express vagueness in environmental issues.

We discuss the best way to deal with uncertainties in the environmental field and give examples of probabilistic and fuzzy-logic approaches applied to environmental risk assessment.     

Improved stability of OPALMON tablets under humid conditions. III: Application of the rotary vacuum drying method to dry Opalmon tablets

In stability studies on moisture-resistant Opalmon tablets in press-through-packages (PTP), which were placed in aluminum bags, we found that the degradation rate of the dextran formulation is faster than that of the lactose formulation. The fast degradation of the dextran formulation is attributed to residual moisture in the package because drying the tablets before packaging suppressed the degradation and there is a good correlation between the stability of the drug and the water-activity of the tablets. Therefore, we developed a new drying method for the tablets, i.e. the rotary vacuum drying method, and investigated the effects of the operating conditions such as heating temperature, rotation speed, and vacuum degree on the drying time, and the appearance of the tablets. Using the rotary vacuum drying method, the tablets were dried over a short time (30 min) on a mass production scale so that the water activity was less than 0.03. Furthermore, the tablets suffered negligible damage such as breaking and chipping during the drying process. These results indicate that the rotary vacuum drying method is useful for drying tablets on mass production scales.