Swelling and Salt Formation in Ibuprofen and Tranexamic Acid-Containing Tablets during High-Temperature Storage

Ibuprofen (IBP)- and Tranexamic acid (TXA)-containing tablets are known to swell when stored at high temperatures, but the mechanism of swelling is unknown. In this study, we investigated the possible mechanism of swelling with high-temperature storage. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) analyses showed that a new complex was formed in swollen tablets, when stored at 50 °C for 60 days. Additionally, we prepared single crystals of IBP and TXA, and analyzed them using single crystal X-ray diffractometry (SCXRD), to identify the new complex formed during storage. This revealed that the single crystal was a salt consisting of IBP and TXA. The PXRD peak of the salt simulated by SCXRD matched that of the PXRD peak of the swollen tablet after storage. These results suggest a close relationship between the swelling and crystal structures of IBP and TXA

Small interfering RNA delivery into the liver by cationic cholesterol derivative-based liposomes

<p><i>Purpose</i>: Previously, we reported that the cationic liposomes composed of a cationic cholesterol derivative, cholesteryl (2-((2-hydroxyethyl)amino)ethyl)carbamate (OH-C-Chol) and 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphoethanolamine (DOPE) (termed LP-C), could deliver small interfering RNAs (siRNAs) with high transfection efficiency into tumor cells. In this study, to develop a liposomal vector for siRNA delivery <i>in vivo</i>, we prepared the poly(ethyleneglycol) (PEG)-modified cationic liposomes (LP-C-PEG) and evaluated their transfection efficiency <i>in vitro</i> and <i>in vivo</i>.</p> <p><i>Materials and methods</i>: We prepared LP-C-PEG/siRNA complexes (LP-C-PEG lipoplexes) formed in water or 50 mM NaCl solution, and evaluated their siRNA biodistribution and gene silencing effect in mice after intravenous injection.</p> <p><i>Results</i>: LP-C-PEG lipoplexes strongly exhibited <i>in vitro</i> gene silencing effects in human breast tumor MCF-7 cells as well as LP-C lipoplexes. In particular, formation of LP-C and LP-C-PEG lipoplexes in the NaCl solution increased the cellular association. When LP-C-PEG lipoplexes with Cy5.5-labeled siRNA formed in water or NaCl solution were injected into mice, accumulation of the siRNA was observed in the liver. Furthermore, injection of LP-C-PEG lipoplexes with ApoB siRNA could suppress ApoB mRNA levels in the liver and reduce very-low-density lipoprotein/low-density lipoprotein levels in serum compared with that after Cont siRNA transfection, although the presence of NaCl solution in forming the lipoplexes did not affect gene silencing effects <i>in vivo</i>.</p> <p><i>Conclusions</i>: LP-C-PEG may have potential as a gene vector for siRNA delivery to the liver.</p

Comparison of the usability of an automatic sleep staging program via portable 1-channel electroencephalograph and manual sleep staging with traditional polysomnography

Automatic algorithms are a proposed alternative to manual assessment of polysomnography data for analyzing sleep structure; however, none are acceptably accurate for clinical use. We investigated the feasibility of an automated sleep stage scoring system called Sleep Scope, which is intended for use with portable 1-channel electroencephalograph, and compared it with the traditional polysomnography scoring method. Twenty-six outpatients and fourteen healthy volunteers underwent Sleep Scope and polysomnography assessments simultaneously. Polysomnography records were manually scored by three sleep experts. Sleep Scope records were scored using a dedicated auto-staging algorithm. Sleep parameters, including total sleep time, sleep latency, wake after sleep onset, and sleep efficiency, were calculated. The epoch-by-epoch pairwise concordance based on the classification of sleep into five stages (i.e., wake, rapid eye movement, N1, N2, and N3) was also evaluated after validating homogeneity and bias between Sleep Scope and polysomnography. Compared with polysomnography, Sleep Scope seemed to overestimate sleep latency by approximately 3 min, but there was no consistent tendency in bias in other sleep parameters. The Κ values ranged from 0.66 to 0.75 for experts’ inter-rater polysomnography scores and from 0.62 to 0.67 for Sleep Scope versus polysomnography scores, which indicated sufficient agreement in the determination of sleep stages based on the Landis and Koch criteria. We observed sufficient concordance between Sleep Scope and polysomnography despite lower concordance in sleep disorder patients. Thus, this auto-staging system might serve as a novel clinical tool for reducing the time and expenses required of medical staff and patients