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STUDY OBJECTIVES: The purpose of this study was to examine the degree of short-term stability of polysomnographic (PSG) measured sleep parameters and the overall differences between individuals with comorbid nightmares and insomnia compared to those with chronic insomnia disorder alone or good sleeping controls across four nights in the sleep lab. METHODS: A total of 142 good sleeping controls, 126 chronic insomnia alone, and 24 comorbid insomnia/nightmare participants underwent four consecutive nights of 8-hour PSG recordings. Outcomes included sleep continuity, architecture, and REM-related parameters across nights one through four. Intraclass correlation coefficients with mixed-effect variances and repeated-measure analysis of covariance were used, respectively, to determine short-term stability as well as between-participants and time-by-group interaction effects. RESULTS: Wake after sleep onset and stage 1 showed "poor stability" in the comorbid insomnia/nightmare group compared to "moderate stability" in the good sleeping controls and chronic insomnia alone group. Significant between-group effects (all ps < .05) showed that the comorbid insomnia/nightmare group took longer to fall asleep and had a greater first-night-effect in stage 1 compared to good sleeping controls and chronic insomnia alone group; in addition, the comorbid insomnia/nightmare and insomnia alone groups slept shorter, with fewer awakenings and REM periods, compared to the good sleeping controls. CONCLUSIONS: Nightmares are associated with abnormal sleep above and beyond REM disruption, as sleep continuity was the primary aspect in which poor stability and group differences emerged. The greater inability to fall asleep and instability of sleep fragmentation in those with comorbid insomnia/nightmares compared to chronic insomnia alone may be attributed to the impact of presleep anticipatory anxiety and nightmare-related distress itself. CLINICAL TRIAL INFORMATION: The data analyzed in this study does not come from any current or previous clinical trials. Therefore, there is no clinical trial information to report.

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Several aromatic amines (AAs) are established by the International Agency for Research on Cancer as carcinogenic (group 1) or probable/possible carcinogens to humans (group 2A/2B). AAs can be found in mainstream and sidestream smoke from combustible tobacco products, as well as in certain environmental pollution and occupational exposure from several chemical industry sectors. Exposure to AAs can be estimated by measuring their concentrations in urine; however, information about the short-term and long-term stabilities of AAs in urine need to be characterized before conducting large-scale population studies on AA exposure and the potentially harmful effects of AA exposure. In this report, the storage stability of o-toluidine, 2,6-dimethylaniline, o-anisidine, 1-aminonaphthalene, 2-aminonaphthalene, and 4-aminobiphenyl fortified in pooled, filtered, non-smokers' urine is analyzed by isotope dilution gas chromatography-triple quadrupole mass spectrometry (ID GC-MS/MS). The six AAs were measured in urine samples stored at ~20 °C (collection temperature), 4 °C and 10 °C (short-term transit temperatures), and -20 °C and -70 °C (long-term storage temperatures) over a 10-day period. All six analytes were stable for 10 days at transit and long-term storage temperatures but showed reduced recovery at 20 °C. The instability of the target AAs at 20 °C suggests that immediate storage of freshly voided urine at low temperatures is needed to attenuate degradation. A subset of the urine samples was analyzed following a longer storage duration at -70 °C: all AAs were stable for up to 14 months at this temperature. The stability of the six AAs in urine samples can be maintained at the various temperature levels and storage times expected in a typical study set.

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This paper describes the stability study performed in seawater and seawater extracts (spiked at ~ 200 ng/L) for 23 emerging contaminants. Four different alternatives were tested at six different times (0, 3, 10, 17, 24 and 31 days): (i) seawater at 4 °C, (ii) mixed-mode solid-phase extraction cartridge (Bond Elute Plexa and Strata X-AW) stored at - 20 °C, (iii) polyethersulfone hollow fibre stored at - 20 °C and (iv) methanol extracts once the samples were extracted from PES hollow fibre and stored at - 20 °C. Moreover, the integrity of the supporting polymeric phases was studied by Raman, optical microscopy, differential scanning calorimetric and thermogravimetric analysis. As may be expected, seawater samples showed the lowest stability (losses between 21 and 99%) while methanol extract provides stable results (losses < 30%) over the tested period. In the case of solid-phase cartridges, the stability profile showed an average loss of 7% while, in polyethersulfone hollow fibres, losses up to 58% were observed. Finally, we were able to relate the lower efficiency of polyethersulfone fibres with the wettability of this material based on the thermogravimetric analysis.

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The aim of this study was to prepare and evaluate in vitro and in vivo; Diltiazem-Hydrochloride (DTZ) in sustained-release matrix tablets. Stability of DTZ tablets prepared with polyethylene oxide (MWs 900 000, 4 000 000, and 8 000 000) with or without addition of electrolytes was carried-out for 1-month, under short-term storage at 40 °C/75% RH. Stability was evaluated by DTZ content, DSC and drug release using the Flow-Through Cell (USP # IV). The majority of stored tablets were stable for 1-month under short-term storage with respect to DTZ content and drug release. DSC curves of stored samples showed appearance of new exothermic peak after 1-month storage at 40 °C/75% RH, which was not observed after 5 years storage at room temperature. A selected formula was tested in vivo against reference product on eight healthy human volunteers. DTZ-plasma profiles were different between the two formulae. However, no statistically significant differences were detected between Cmax, AUC0-48 and AUC0-∞. The two products were therapeutically in-equivalent, as 90% confidence intervals "T/R" were 88.82-205.76, 91.40-139.94, and 93.73-134.97 for Cmax, AUC0-48 and AUC0-∞, respectively. This study highlighted possible differences observed between the two regimes frequently applied for stability testing.

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OBJECTIVE: Tandem mass spectrometry is increasingly used in the Middle East in newborn screening for inborn errors of metabolism using dried blood spots. The sensitivity and specificity of this system for analyzing fatty and amino acids, screening for more than 40 metabolic conditions, is known. However, the short term stability of acylcarnitines and amino acids in dried blood spots in extreme heat and humid conditions is not well documented. We examined the short term effect of heat and humidity on the levels of 7 amino acids and 10 acylcarnitines used in newborn screening for inherited metabolic disorders. METHODS: Dried blood spots were exposed with humidity <30% to temperatures of 4, room temperature, 37° C, and 45, and also with humidity >70% at 37° C and 45. Amino acids and acylcarnitines in the dried blood spots were analyzed by tandem mass spectrometry. RESULTS: During the eight days of the study in high temperature and high humidity storage, most acylcarnitines and amino acids lost almost 50% of initial concentration. After eight days' exposure at 37 and 45 with humidity >70%, methionine was determined to be the most sensitive, and phenylalanine and leucine were the least sensitive amino acids. At 37 with humidity >70% C6 was the most sensitive and free carnitine (C0) was the least sensitive acylcarnitine; at 45 with humidity >70% C16 was the most sensitive and C0 was the least sensitive. CONCLUSION: Low humidity and low temperature conditions are required for transportation and storage of dried blood spots.

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Nicergoline, a poorly soluble active pharmaceutical ingredient, possesses vaso-active properties which causes peripheral and central vasodilatation. In this study, nanocrystals of nicergoline were prepared in an aqueous solution of polysorbate 80 (nanosuspension) by using four different laboratory scale size reduction techniques: high pressure homogenization (HPH), bead milling (BM) and combination techniques (high pressure homogenization followed by bead milling HPH + BM, and bead milling followed by high pressure homogenization BM + HPH). Nanocrystals were investigated regarding to their mean particles size, zeta potential and particle dissolution. A short term physical stability study on nanocrystals stored at three different temperatures (4, 20 and 40 °C) was performed to evaluate the tendency to change in particle size, aggregation and zeta potential. The size reduction technique and the process parameters like milling time, number of homogenization cycles and pressure greatly affected the size of nanocrystals. Among the techniques used, the combination techniques showed superior and consistent particle size reduction compared to the other two methods, HPH + BM and BM + HPH giving nanocrystals of a mean particle size of 260 and 353 nm, respectively. The particle dissolution was increased for any nanocrystals samples, but it was particularly increased by HPH and combination techniques. Independently to the production method, nicergoline nanocrystals showed slight increase in particle size over the time, but remained below 500 nm at 20 °C and refrigeration conditions.

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The aim of present study were to arrest the problem of content uniformity without the use of harmful organic solvent and to improve ex vivo permeability of captopril, a low dose class III drug as per biological classification system. Eutectic mixture of camphor and menthol was innovatively used in the work. Captopril solution in eutectic mixture was blended with Avicel PH 102 and then the mixture was blended with mannitol in different ratios. Formulated batches were characterized for angle of repose and Carr's index. A selected batch was filled in hard gelatin capsule. Tablet dosage form was also developed. Capsules and tablets were characterized for in vitro drug release in 0.1N HCl. Additionally, the captopril tablets were analyzed for content uniformity and ex vivo drug permeation study using rat ileum in modified apparatus. The measurement of angle of repose and Carr's index revealed that the powder blend exhibited good flow property and compressibility. The captopril capsules and tablets exhibited immediate drug release in 0.1 N HCl. The captopril tablets passed content uniformity test as per IP 1996. Ex vivo permeation of captopril, formulated with eutectic mixture, was faster than control. The permeation was increased by 15% at the end of 3 h. Tablets and capsule exhibited reasonable short term stability with no considerable change in performance characteristics.