Development of Fast Disintegrating Tablets Containing Loxoprofen Sodium by HYDROFLASH Manufacturing Method.

In order to create and offer superior pharmaceuticals for consumers who wish to be relieved of headache and fever as soon as possible, we established HYDROFLASH manufacturing method that enables us to offer fast disintegration tablets containing loxoprofen sodium (LX), which are difficult to disintegrate. As a result of screening excipients, tablets using mannitol showed the fastest disintegration time, about 2 min. From the result of viscosity measurement, we found that LX produced higher viscosity when dissolved in water. This suggests that tablets containing LX disintegrate slower by inhibiting the penetration of water into the tablet due to the viscosity caused of LX. Therefore, we created a manufacturing method to make it easy for water to penetrate the tablet. It is possible to achieve fastest disintegration in about 30 s for tablets containing LX by granulating in a fluidized-bed with spraying of the dispersion of light anhydrous silicic acid (LASA). LX-containing tablets manufactured by the HYDROFLASH method disintegrated immediately after contact with water. Furthermore, it was observed that LASA was uniformly dotted on the surface of tablets by HYDROFLASH method, compared with other manufacturing methods. We considered that by fluidized-bed granulation with LASA dispersion (HYDROFLASH manufacturing method), water permeates through LASA on the tablet surface regardless of viscosity of LX. Futhermore, LX-containing tablets by the HYDROFLASH method showed that the dissolution rate of LX was nearly 100% at 5 min after starting the test. We considered that the initial dissolution became faster because of the fast disintegration.

Comparisons of the efficiency of respiratory rate monitoring devices and acoustic respiratory sound during endoscopic submucosal dissection.

During moderate sedation for gastrointestinal endoscopic submucosal dissection (ESD), monitoring of ventilatory function is recommended. We compared the following techniques of respiratory rate (RR) measurement with respiratory sound (RRa): capnography (RRc), thoracic impedance (RRi), and plethysmograph (RRp). This study enrolled patients aged ≥ 20 years who underwent esophageal (n = 19) and colorectal (n = 5) ESDs. RRc, RRi, RRp, and RRa were measured by Capnostream™ 20P, BSM-2300, Nellcor™ PM1000N, and Radical-7®, respectively. In total, 413 RR data were collected from the esophageal ESD group and 114 RR data were collected from the colorectal ESD group. Compared with RRa during colorectal ESD, that during esophageal ESD had larger bias [95% limit of agreement (LOA)] with RRc [1.9 (- 11.0-14.8) vs. - 0.4 (- 2.9-2.2)], RRi [9.4 (- 16.8-9.4) vs. - 1.5 (- 12.0-8.9)], and RRp [0.3 (- 5.7-6.4) vs. 0.2 (- 3.2-3.6)]. Of the correct RR values displayed during esophageal ESD, > 90% were measured as RRa and RRp. Moreover, RRc was a useful parameter during colorectal ESD. To maximize patient safety during ESD under sedation, endoscopists and medical staff should know the feature and principle of the devices used for RR measurement. During esophageal ESD, RRa and RRp may be a good parameter to detect bradypnea or apnea. RRc, RRa and RRp are useful for reliable during colorectal ESD.Trial registration UMIN-CTR (UMIN000025421).

Forehead Regional Oxygen Saturation (rSO2)-Related Ear-Level Arterial Pressure and Lower Thigh rSO2 in the Steep Trendelenburg Position with CO2 Pneumoperitoneum and the Beach Chair Position.

Introduction Regional oxygen saturation (rSO2) reflects tissue perfusion. This observational study aimed to examine the change in the forehead and lower thigh rSO2 associated with intraoperative posture, anesthesia regimen, or mean arterial pressure (mAP) at heart and external auditory meatus (ear) levels. Methods Patients undergoing robot-assisted laparoscopic radical prostatectomy in the Trendelenburg position at 30° with pneumoperitoneum (TPP) or arthroscopic shoulder surgery in the beach chair position at 70° (BCP) under desflurane-remifentanil (D/R) or propofol-remifentanil (P/R) anesthesia were examined. Bilateral forehead and lower thigh rSO2 values and mean radial artery pressure were measured simultaneously at heart and ear levels. Results In TPP, there were no differences under anesthesia regimens in the forehead or lower thigh rSO2change, although one patient with an absolute lower thigh rSO2 of ≤50% in the lithotomy position complained of transient limb pain. No correlation was observed between rSO2 and mAP. In BCP, forehead rSO2 decreased and lower thigh rSO2 increased under either of the anesthesia regimens. The coefficient of correlation between forehead rSO2 andheart-level and ear-level mAP was 0.341 and 0.236, respectively. Conclusions There were no differences under anesthesia regimens in the changes of forehead rSO2 and lower thigh rSO2. In TPP, significant changes in forehead rSO2 and lower thigh rSO2 were not observed. Monitoring lower thigh rSO2 might be useful for preventing lower extremity pain. In BCP, forehead rSO2 decreased and lower thigh rSO2 increased from the supine position to the BCP. To prevent brain damage, anesthesiologists should pay attention to heart- and ear-level mAP.

Comparison of Nellcor™ PM1000N and Masimo Radical-7® for detecting apnea in volunteers.

PURPOSE: Although capnography is considered the gold standard for monitoring of ventilation, it may not work accurately in some situations. We compared the performance of two non-invasive continuous respiratory rate (RR) monitors that are alternatives for the detection of respiratory depression. METHODS: Fifty healthy volunteers ≥20 years old were enrolled in this study. After monitoring of the volunteers was started by the Masimo Radical-7® and Nellcor™ PM1000N, they breathed at the rate of 12 breaths/min for 3 min and then stopped breathing. As soon as the apnea alarm of either monitor went off, breathing was resumed at the same rate. This entire procedure was repeated three times. The data collected every 30 s included the RR, pulse rate (PR) and oxygen saturation (SpO2). The times of alarm on, alarm off and reappearance of RR on the monitor screens were also recorded. RESULTS: The biases of the RR, PR and SpO2 measurements from the two monitors were 0.5, 0.2 and -0.4, respectively. Of 143 procedures that stopped breathing for more than 30 s, 114 and 15 alarms were shown by the Masimo Radical-7® and Nellcor™ PM-1000N monitors, respectively. Most alarms of the Nellcor™ PM1000N followed from SpO2 <90%. Conversely, most alarms of the Masimo Radical-7® were caused by RR <10 breaths/min. Times to alarm on, alarm off and display of RR measured by the Masimo Radical-7® monitor were significantly shorter than the Nellcor™ PM-1000N monitor. CONCLUSIONS: The Masimo Radical-7® monitor provides better detection of apnea in volunteers than the Nellcor™ PM-1000N.

Is the Ambu aScope 3 Slim single-use fiberscope equally efficient compared with a conventional bronchoscope for management of the difficult airway?

STUDY OBJECTIVE: The study objective was to evaluate whether the single-use fiberoptic bronchoscope (FOB), Ambu aScope 3 Slim, was equally efficient compared with the conventional reusable FOB, Olympus LF-GP, for nasal fiberoptic intubation in a manikin. DESIGN: A randomized crossed-over study. SETTING: The postanesthesia care unit of Tokyo Women's Medical University Hospital. SUBJECTS: Twenty anesthesiologists who have experienced >50 one-lung ventilation thoracic surgery procedures were invited to participate in this study. INTERVENTIONS: A 6.5-mm internal diameter cuffed endotracheal tube (ET) was inserted into the manikin under Ambu aScope 3 Slim (group A) or Olympus LF-GP (group C) guidance. MEASUREMENTS: The following time parameters from the beginning of FOB insertion through a nostril were compared between groups: until vocal cord visualization (T1); visualization of the carina (T2); and proper ET placement, as confirmed by the distance of the ET tip to carina (T3). MAIN RESULTS: Mean (SD) T1 in group A and group C were 20 seconds (17 seconds) and 14 seconds (12 seconds), respectively (P= .1050). Mean (SD) T2 in group A and group C were 40 seconds (29 seconds) and 25 seconds (15 seconds), respectively (P= .0287). Mean (SD) T3 in group A and group C were 70 seconds (33 seconds) and 50 seconds (22 seconds), respectively (P= .0098). One case in group A had failed intubation CONCLUSIONS: The Ambu aScope 3 Slim required more time to intubate than the conventional reusable FOB. It requires more rigidity, similar to the conventional FOB for management of the difficult airway.

Adenosine triphosphate bioluminescence assay for monitoring contamination of the working environment of anaesthetists and cleanliness of the operating room.

Anaesthetists possibly contribute to the spread of infections during anaesthesia. The adenosine triphosphate (ATP) bioluminescence assay is an easy-to-perform, on-the-spot assay that provides objective data; therefore, using the LuciPac®Pen and the Lumitester PD-20®System, we assessed contamination of the working environment of anaesthetists before and after surgery as well as their hands at the time of each procedure during induction and extubation. Similarly, cleanliness of the operating room was evaluated using this assay to determine whether it is useful to assess the effectiveness of the routine cleaning protocols followed after surgery. ATP concentrations in the working environment of anaesthetists and their hands increased during surgery. In addition, ATP concentrations within the working environment decreased after routine cleaning with ethanol or accelerated hydrogen peroxide; however, there were no differences in the number of sites with ATP concentrations >500 relative light units before and after cleaning. This method is useful to evaluate contamination of the working environment of anaesthetists; nevertheless, it is prudent to evaluate the effectiveness of routine cleaning protocols because ATP bioluminescence assays are influenced by the use of various disinfectants at varying concentrations.

Dual roles of nuclear receptor liver X receptor α (LXRα) in the CYP3A4 expression in human hepatocytes as a positive and negative regulator.

CYP3A4 is a major drug-metabolizing enzyme in humans, whose expression levels show large inter-individual variations and are associated with several factors such as genetic polymorphism, physiological and disease status, diet and xenobiotic exposure. Nuclear receptor pregnane X receptor (PXR) is a key transcription factor for the xenobiotic-mediated transcription of CYP3A4. In this study, we have investigated a possible involvement of liver X receptor α (LXRα), a critical regulator of cholesterol homeostasis, in the hepatic CYP3A4 expression since several recent reports suggest the involvement of CYP3A enzymes in the cholesterol metabolism in humans and mice. Reporter assays using wild-type and mutated CYP3A4 luciferase reporter plasmids and electrophoretic mobility shift assays revealed that LXRα up-regulated CYP3A4 through the known DNA elements critical for the PXR-dependent CYP3A4 transcription, suggesting LXRα as a positive regulator for the CYP3A4 expression and a crosstalk between PXR and LXRα in the expression. In fact, reporter assays showed that LXRα activation attenuated the PXR-dependent CYP3A4 transcription. Moreover, a PXR agonist treatment-dependent increase in CYP3A4 mRNA levels was suppressed by co-treatment with an LXRα agonist in human primary hepatocytes and HepaRG cells. The suppression was not observed when LXRα expression was knocked-down in HepaRG cells. In conclusion, the present results suggest that sterol-sensitive LXRα positively regulates the basal expression of CYP3A4 but suppresses the xenobiotic/PXR-dependent CYP3A4 expression in human hepatocytes. Therefore, nutritional, physiological and disease conditions affecting LXRα might be one of the determinants for the basal and xenobiotic-responsive expression of CYP3A4 in human livers.