Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying.

A co-amorphous model drug was prepared by the spray-drying (SD) of probucol (PC) and atorvastatin calcium trihydrate salt (ATO) as low water solubility and co-former components, respectively. The physicochemical properties of the prepared samples were characterized by powder X-ray diffraction (PXRD) analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and dissolution tests. Stability tests were also conducted under a stress environment of 40 °C and 75% relative humidity. The results of PXRD measurements and thermal analysis suggested that PC and ATO form a co-amorphous system by SD. Thermal analysis also indicated an endothermic peak that followed an exotherm in amorphous PC and a physical mixture (PM) of amorphous PC and ATO; however, no endothermic peak was detected in the co-amorphous system. The dissolution profiles for PC in the co-amorphous sample composed of PC and ATO were improved compared to those for raw PC crystals or the PM. Stability tests indicated that the co-amorphous material formed by PC and ATO can be stored for 35 d without crystallization, whereas amorphous PC became crystallized within a day. Therefore, co-amorphization of PC and ATO prepared by SD is considered to be a useful method to improve the solubility of PC in water.

Distinguishing true from pseudo hematoma in the cervical spinal canal using postmortem computed tomography.

Spinal cord injury is difficult to detect directly on postmortem computed tomography (PMCT) and it is usually diagnosed by indirect findings such as a hematoma in the spinal canal. However, we have encountered cases where the hematoma-like high-attenuation area in the cervical spinal canal was visible on PMCT, while no hematoma was observed at autopsy; we called it a "pseudo hematoma in the cervical spinal canal (pseudo-HCSC)." In this retrospective study, we performed statistical analysis to distinguish true from pseudo-HCSC. The cervical spinal canal was dissected in 35 autopsy cases with a hematoma-like high-attenuation area (CT values 60-100 Hounsfield Unit (HU)) in the spinal canal from the first to the fourth cervical vertebrae in axial slices of PMCT images. Of these 22 had a hematoma and 13 did not (pseudo-HCSC). The location and length of the hematoma-like high-attenuation and spinal cord areas were assessed on reconstructed PMCT images, true HCSC cases had longer the posterior hematoma-like area and shorter the spinal cord area in the midline of the spinal canal (P < 0.05). Furthermore, we found that true HCSC cases were more likely to have fractures and gases on PMCT while pseudo-HCSC cases were more likely to have significant facial congestion (P < 0.05). We suggest that pseudo-HCSC on PMCT is related to congestion of the internal vertebral venous plexus. This study raises awareness about the importance of distinguishing true HCSC from pseudo-HCSC in PMCT diagnosis, and it also presents methods for differentiation between these two groups.

Progressive Thymic Hyperplasia With Graves' Disease: A Case Report.

We treated a 36-year-old man with thymic hyperplasia complicated with Graves' disease. Thymic hyperplasia was observed on thoracic computed tomography (CT) three months after the onset of thyrotoxicosis symptoms. One month after thiamazole initiation, he displayed drug-induced liver injury and underwent a total thyroidectomy. Seven months after surgery, we observed a dramatic reduction of thymic size associated with normalizing the soluble interleukin-2 receptor (sIL-2R) levels. The rapid development of hyperplasia after the onset of thyrotoxicosis and the restoration in thymus volume after total thyroidectomy associated with suppression of sIL-2R, in this case, suggests the complexity of the pathogenesis of thymic hyperplasia in the thyrotoxicosis.

[Microtaggant Technology for Ensuring Traceability of Pharmaceutical Formulations: Potential for Anti-counterfeiting Measures, Distribution and Medication Management].

The globalization of drug trade has led to the increased production of falsified medicines. In addition, poor medication adherence increases the costs of healthcare. The need to manage medication has given rise to marketing of highly functional networked digital medicine. Therefore, a growing need has emerged to ensure the traceability of pharmaceutical products from shipment to patient distribution. Microtaggant technologies that can encode individual numbers on pharmaceutical products are expected to serve achieving this goal. Taggants are a class of materials that can be applied to an object to make it identifiable, like barcodes and holograms. Since the smaller size of microtaggant make it invisible to naked eyes, it is more difficult to reverse-engineer than conventional taggants. The U.S. Food and Drug Administration (FDA) has established guidelines for the use of microtaggants. Many studies have explored the use of various analytical technologies and materials as the microtaggants. However, the advantages and disadvantages of each method have not been established yet. In this review, recent research on the use of microtaggants for anti-counterfeiting is summarized and compared to current anti-counterfeiting technologies with spectrographic methods, distribution management systems with barcodes, and medication management systems with sensor devices. We also discuss the microtaggants implementation costs and security level.

Physical stability of stealth nanobeacon using surface-enhanced Raman scattering for anti-counterfeiting and monitoring medication adherence: Deposition on various coating tablets.

Microtaggant technologies can encode individual numbers on coating tablet to authenticate pharmaceutical products and, therefore, combat the global spread of falsified medicine. In this study, a novel microtaggant, stealth nanobeacon (NB), with surface-enhanced Raman scattering (SERS) activity was applied to various coating tablets and its physical stability was evaluated. The NBs were composed of a reporter molecule (AH, adenine hydrochloride) and prepared with different sizes of gold nanoparticles (AuNPs). The NBs were directly deposited on the surface of various model coatings (e.g., hydroxypropyl cellulose, hydroxypropyl methyl cellulose, Eudragit® RS30D, ethyl cellulose). To investigate physical stability of the NB on the coating tablets, SERS spectra of the NB after friability test and acceleration test (store at 75% RH, 40 °C) were evaluated using a portable Raman spectrometer. After the friability test, there was no significant decrease in the peak intensity of the SERS signal (PH) for authentication in all samples. In the acceleration test, the SERS signals of the samples were attenuated, but sufficient SERS signal intensity (PH > 70) was maintained in the seven types of coating for authentication. These results demonstrate that the microtaggant NB has the potential to be used for a wide range of coating tablets.

Administration of retinoic acid to pregnant mice increases the number of fetal mouse glomeruli.

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and CKD is a serious global health problem. Low glomerular number is one of the risk factors for CKD; therefore, the glomerular number is associated with the risk of CKD. Increasing the glomerular number above normal levels may reduce the risk of CKD. It has been reported that, in vitro, the addition of retinoic acid (RA) to the culture medium increases the glomerular number. However, there is no report of an increase in glomerular number above normal levels with the addition of RA in vivo. In this study, RA (20 mg/kg) was administered intraperitoneally to pregnant mice once at embryonic day (E) 10.5, E12.5, E14.5, or E16.5. The fetuses were harvested at E18.5 and fetal mouse kidneys were evaluated. Fetal kidney volume and weight were significantly increased in the E16.5 group compared to the control group. The total glomerular number in the E16.5 group was also approximately 1.46 times higher than that in the control group. In summary, we established a method to increase the glomerular number in the fetal kidney by administration of RA to pregnant mice at E16.5. These results will facilitate the investigation of whether CKD risk is reduced when the glomerular number increases above normal.

Design and preparation of nanocomposite acrylate coating agents for binder-free dry coating of 100 µm-sized drug-containing particles and their coating performance.

For binder-free dry particulate coating to prepare controlled-release micron-sized particles, we designed nanocomposite coating agents with the intention to form a core-shell structure composed of two types of acrylic polymers with different glass transition temperatures (Tg) and evaluated their coating performance. A series of nanocomposite acrylic latexes synthesized by emulsion polymerization was freeze-dried after salting-out to create the powder form. An ion-exchange resin loaded with diclofenac sodium (DS, a model drug) (IER-DS) with a median diameter of approximately 100 µm was used as the core particle. Dry coating of the IER-DS with nanocomposite coating agents was carried out using a laboratory-made coating apparatus assisted with mild-intensity vibration and zirconia bead impaction. The coated particles were cured by heating at a temperature 20 °C higher than the Tg for 12 h to complete the film-forming process. It was found that the highest coating efficiency (more than 70%) and a remarkably prolonged release period of the drug (the time required for 50% release reached approximately 12 h) could be achieved when nanocomposite coating agents with a soft polymeric core (Tg = 30 °C) and a hard polymeric shell (Tg = 80 °C) were applied. In contrast, nanocomposite coating agents with a combination of a hard polymeric core and a soft polymeric shell resulted in lower coating efficiency. These results demonstrate that nanocomposite polymeric coating agents composed of a soft core and a hard shell are effective for the production of drug-loaded microparticles with a prolonged release function by a binder-free dry-coating process.

Global pattern of interkinetic nuclear migration in tracheoesophageal epithelia of the mouse embryo: Interorgan and intraorgan regional differences.

Interkinetic nuclear migration (INM) is an apicobasal (AB) polarity-based regulatory mechanism of proliferation/differentiation in epithelial stem/progenitor cells. We previously documented INM in the endoderm-derived tracheal/esophageal epithelia at embryonic day (E) 11.5 and suggested that INM is involved in the development of both organs. We here investigated interorgan (trachea vs esophagus) and intraorgan regional (ventral vs dorsal) differences in the INM mode in the tracheal and esophageal epithelia of the mouse embryo. We also analyzed convergent extension (CE) and planar cell movement (PCM) in the epithelia based on cell distribution. The pregnant C57BL/6J mice were intraperitoneally injected with 5-ethynyl-2'-deoxyuridine at E11.5 and E12.5 and were sacrificed 1, 4, 6, 8, and 12 hours later to obtain the embryos. The distribution of labeled cell nuclei along the AB axis was chronologically analyzed in the total, ventral, and dorsal sides of the epithelia. The percentage distribution of the nuclei population was represented by histogram and the chronological change was analyzed statistically using multidimensional scaling. The interorgan comparison of the INM mode during E11.5-E12.0, but not E12.5-E13.0, showed a significant difference. During E11.5-E12.0 the trachea, but not the esophagus, showed a significant difference between ventral and dorsal sides. During E12.5-E13.0 neither organ showed regional differences. CE appeared to occur in both organs during E11.5-E12.0 while PCM was unclear in both organs. These findings suggest a difference between the trachea and esophagus, and a regional difference in the trachea, not in the esophagus, in the INM mode, which may be related with the later differential organogenesis/histogenesis of these organs.

Poor Walking Speed Is Associated With Higher Segment-Specific Arterial Stiffness in Older Adult Japanese Community Dwellers: A Cross-Sectional Study.

Walking speed as one index of gait ability is an important component of physical fitness among older adults. Walking speed-arterial stiffness relationships have been studied, but whether poor walking speed is associated with higher segment-specific arterial stiffness in older adults is unclear. We thus aimed to examine the relationship between walking speed and segmental arterial stiffness among older community dwellers. This study was a cross-sectional study of 492 older Japanese community dwellers (age range, 65 to 96 years). Heart-brachial PWV (hbPWV), brachial-ankle PWV (baPWV), heart-ankle PWV (haPWV), and cardio-ankle vascular index (CAVI) were used as arterial stiffness indices. Walking speed, strength, flexibility, and cognitive function were also assessed. The participants were categorized into low (Slow), middle (Middle), and high (Fast) tertiles according to walking speed. The CAVI and baPWV were significantly lower in Fast than in Slow. Significant decreasing trends in CAVI and baPWV and a tendency toward decreasing trend in haPWV were observed from Slow to Fast, whereas hbPWV did not significantly differ among tertiles and no trend was evident. The results remained significant after normalizing CAVI and PWVs for multicollinearity of arterial stiffness indices and major confounding factors, such as age, gender, body mass index, blood pressure, cognitive function, and each physical fitness. Therefore, these findings suggest that poor walking speed is associated with higher segment-specific arterial stiffness of the central and lower limbs, but not of upper, in older adult community dwellers.

Crystallographic evaluation of the conformation of quetiapine included in ß-cyclodextrin.

Single-crystal X-ray diffraction and theoretical calculations were conducted for insights into the ß-cyclodextrin (ß-CD)-quetiapine inclusion complex structure. ß-CD and quetiapine form a host-guest inclusion complex at a ratio of 2:1 in which the ß-CD molecules form head-to-head dimers with their secondary hydroxyl groups linked by multiple hydrogen bonds. Quetiapine is totally contained within the ß-CD cavity and exhibits two kinds of disorder (parts 1 and 2) in opposite directions in the ß-CD complex. To clarify the mobility of the guest molecule in the ß-CD cavity, theoretical molecular conformational calculations, crystal optimization and crystal energy calculations were conducted using CONFLEX software. The results of theoretical molecular conformation calculations showed that the mobility of quetiapine is restricted because its tricyclic structure is covered by ß-CD. The results of crystal energy calculations indicated that the conformation of disorder part 1, which has high occupancy, was more stable.

Negative Mood States Are Related to the Characteristics of Facial Expression Drawing: A Cross-Sectional Study.

An assessment of mood or emotion is important in developing mental health measures, and facial expressions are strongly related to mood or emotion. This study thus aimed to examine the relationship between levels of negative mood and characteristics of mouth parts when moods are drawn as facial expressions on a common platform. A cross-sectional study of Japanese college freshmen was conducted, and 1,068 valid responses were analyzed. The questionnaire survey consisted of participants' characteristics, the Profile of Mood States (POMS), and a sheet of facial expression drawing (FACED), and the sheet was digitized and analyzed using an image-analysis software. Based on the total POMS score as an index of negative mood, the participants were divided into four groups: low (L), normal (N), high (H), and very high (VH). Lengths of drawn lines and between both mouth corners were significantly longer, and circularity and roundness were significantly higher in the L group. With increasing levels of negative mood, significant decreasing trends were observed in these lengths. Convex downward and enclosed figures were significantly predominant in the L group, while convex upward figures were significantly predominant and a tendency toward predominance of no drawn mouths or line figures was found in the H and VH groups. Our results suggest that mood states can be significantly related to the size and figure characteristics of drawn mouths of FACED on a non-verbal common platform. That is, these findings mean that subjects with low negative mood may draw a greater and rounder mouth and figures that may be enclosed and downward convex, while subjects with a high negative mood may not draw the line, or if any, may draw the line shorter and upward convex.

Optimization of ionic liquid-incorporated PLGA nanoparticles for treatment of biofilm infections.

Ionic liquids (ILs) containing imidazolium cations have a number of useful properties, such as high permeability to cells, high antimicrobial activity, and good biocompatibility. With the aid of ILs, transdermal delivery, solubilization of poorly soluble drugs were developed and therapeutic effects were improved. In this work, 1­butyl­3­methylimidazolium hexafluorophosphate-incorporated, chitosan-modified, submicron-sized poly(dl­lactide­co­glycolide) (PLGA) nanoparticles (NPs) were prepared using the emulsion solvent diffusion method for the treatment of biofilm infections. Prepared IL-incorporated PLGA NPs using surfactants such as Tween-80 and poloxamer-188 showed a high antibacterial activity to the bacterial cells under the biofilm. Additionally, antibacterial mechanism of IL-incorporated PLGA NPs was revealed by annular dark field scanning transmission electron microscopy combined a simple sample pretreatment method. We established a drug delivery system using IL-incorporated PLGA NPs to enhance the potential of polymeric nanocarriers for treating biofilm infections.

Evaluation of Tumor Tissue Fixation Effects of Formulation Modified Mohs Pastes in Mice and Their Water-Absorbing Properties.

Mohs paste (MP) is a hospital preparation containing zinc hydrochloride and zinc oxide starch. It is a topical medication used to fixate tissues for the removal of inoperable skin tumors and the management of hemorrhage and exudates, and to prevent foul odor resulting from secondary infections. However, it has problems, such as changes in hardness and viscoelasticity with time and liquefaction by exudate. It has been reported that the modified MP with D-sorbitol (S-MP) and the modified MP using the cellulose instead of starch (C-MP) have excellent physicochemical stability and better handling than original MP (O-MP). In this study, the effect of prescription improvement of MP on the pharmacological effect was examined with reference to water absorbing property, and its tumor tissue invasion fixation depth as an indicator. In the S-MP and C-MP, the amounts of water absorption did not differ significantly from those in the O-MP. The hardness of S-MP was decreased and liquefied like O-MP after absorbing water. In contrast, C-MP retained its form even after water absorption. The subcutaneous tumors in mice treated with modified MP formulations were measured for invasion fixation depth at 6 and 24 h after application. And the tissue status was observed using computed tomography. In all MPs, invasion fixation depth increased depending on application time. S-MP and O-MP depths did not differ significantly. The invasion depths of the C-MP significantly increased compared with those in the O-MP. These results suggest that C-MP had a high tissue fixation rate.

Increasing levels of daily physical activity for arterial stiffness reduction in older women: a community-based pilot study.

BACKGROUND: The recent Japanese official physical activity (PA) guidelines for health promotion recommend increasing PA by 10 minutes per day (Plus 10), which generally corresponds to about 1000 steps per day. However, whether habitually increasing PA in daily life improves arterial stiffness in older people is unclear. The present study aimed to examine the effects of habitually increasing PA during an intervention on arterial stiffness in older women. METHODS: Twenty-one older women (age, 76±1 years) participated in supervised group activity and seated exercise for 60 min per session, once each week during an 8-week intervention. The women wore an activity monitor for 1 week to determine baseline values and for the 8 weeks of intervention. Arterial stiffness was assessed before and after the intervention using the Cardio-Ankle Vascular Index (CAVI). RESULTS: Based on changes in steps between baseline and the intervention, the participants were assigned to control (<1000 steps/day, N.=14) or PA-increased (≥1000 steps/day, N.=7) groups with changes of -138±198 steps/day and 2,047±580 steps/day, respectively. The CAVI was significantly reduced only in the PA-increased group (Pre, 9.2±0.2; Post, 9.0±0.2 units), and changes in CAVI were significantly inversely correlated with changes in step counts (rs=-0.62). CONCLUSIONS: Habitually increasing PA in daily life during 8-week intervention can induce a small but significant reduction in arterial stiffness among older women.

Improvement in the water solubility of drugs with a solid dispersion system by spray drying and hot-melt extrusion with using the amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and d-mannitol.

The aim of this study was to prepare and characterize solid dispersion particles with a novel amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, as a water-soluble carrier. Solid dispersion particles were prepared by hot-melt extrusion and spray drying. Indomethacin (IMC) was used as a model comprising drugs with low solubility in water and d-mannitol (MAN) was used as an excipient. The physicochemical properties of prepared particles were characterized by scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, FTIR spectra analysis, and drug release studies. Stability studies were also conducted under stress conditions at 40°C, 75% relative humidity. We found that dissolution behavior of the original drug crystal could be improved by solid dispersion with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer. The PXRD pattern and thermal analysis indicated that the solid dispersion prepared with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC was in an amorphous state. FTIR spectra analysis indicated that the interaction manner between the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC may differ with the preparation method and formulation of solid dispersions. Stability studies proved that the amorphous state of IMC in solid dispersion particles was preserved under stress conditions for more than two weeks.

Interkinetic nuclear migration in the tracheal and esophageal epithelia of the mouse embryo: Possible implications for tracheo-esophageal anomalies.

Interkinetic nuclear migration (INM) is a cell polarity-based phenomenon in which progenitor cell nuclei migrate along the apico-basal axis of the pseudostratified epithelium in synchrony with the cell cycle. INM is suggested to be at least partially cytoskeleton-dependent and to regulate not only the proliferation/differentiation of stem/progenitor cells but also the localized/overall size and shape of organs/tissues. INM occurs in all three of the germ-layer derived epithelia, including the endoderm-derived gut. However, INM has not been documented in the esophagus and respiratory tube arising from the anterior foregut. Esophageal atresia with or without trachea-esophageal fistula (EA/TEF) is a relatively common developmental defect. Transcription factors and signaling molecules have been implicated in EA/TEF, but the etiology of EA/TEF-which has been suggested to involve cell polarity-related mechanisms-remains highly controversial. In the present study, we first examined whether INM exists in the trachea and esophagus of mouse embryos at embryonic day 11.5 (E11.5), just after separation of the two tubes from the anterior foregut. By labeling the DNA-synthesizing stem cell nuclei with 5-ethynyl-2'-deoxyuridine, a nucleotide analogue, and statistically analyzing chronological changes in the distribution pattern of the labeled nuclei by using multidimensional scaling, we showed the existence of INM in both the esophagus and trachea, with differences in the INM magnitude and cycle pattern. We further showed morphological changes from the INM-based pseudostratified single layer to the stratified multilayer in the esophageal epithelium in association with a temporal loss/perturbation of AB polarity, suggesting a possible relation with the pathogenesis of EA/TEF.

Cyclodextrins: structure, physicochemical properties and pharmaceutical applications.

Since their discovery over 100 years ago cyclodextrins (CDs) have been the subject of numerous scientific publications. In 2016 alone CDs were the subject of over 2200 research articles published in peer-reviewed journals and mentioned in over 2300 patents and patent applications, many of which were on pharmaceutical applications. Natural CDs and their derivatives are used as enabling pharmaceutical excipients that enhance aqueous solubility of poorly soluble drugs, increase drug permeability through biological membranes and improve drug bioavailability. Unlike conventional penetration enhancers, their hydrophilic structure and high molecular weight prevents them from penetrate into lipophilic membranes leaving biological membranes intact. The natural CDs and some of their derivatives have monographs in pharmacopeias and are also commonly used as food additives and in toiletry products. CDs form inclusion complexes with lipophilic moieties of hydrophobic drugs. Furthermore, CDs are able to form non-inclusion complexes and self-assembled aggregates; small and large complex aggregates with micellar-like structures that can enhance drug solubility. Excipients commonly used in pharmaceutical formulations may have additive or inhibiting effect on the CD solubilization. Here various methods used to investigate CD aggregate formation are reviewed as well as techniques that are used to increase the solubilizing effects of CDs; methods that enhance the apparent intrinsic solubility of drugs and/or the complexation efficacy and decrease the amount of CD needed to develop CD-containing pharmaceutical formulations. It will be explained how too much or too little CD can hamper drug bioavailability, and the role of CDs in solid dosage forms and parenteral formulations, and examples given on how CDs can enhance drug delivery after ocular, nasal and pulmonary administration.

Crystallographic and theoretical studies of an inclusion complex of ß-cyclodextrin with fentanyl.

The crystal structure of an inclusion complex of ß-cyclodextrin (ß-CD) with fentanyl was determined by single crystal X-ray diffraction analysis. The crystal belongs to the triclinic space group P1 and the complex comprises one fentanyl, two ß-CD, and several water molecules. ß-CD and fentanyl form a host-guest inclusion complex at a ratio of 2:1 and the asymmetric unit of the complex contains two host molecules (ß-CDs) in a head-to-head arrangement that form dimers through hydrogen bonds between the secondary hydroxyl groups of ß-CD and one guest molecule. Fentanyl is totally contained within the ß-CD cavity and the structure of the phenylethyl part of fentanyl inside the dimeric cavity of the complex is disordered. Furthermore, theoretical molecular conformational calculations were conducted to clarify the mobility of the guest molecule in the ß-CD cavity using CONFLEX software. Crystal optimization and crystal energy calculations were also conducted. The results of the theoretical calculations confirmed that the conformation of disorder part 1, which was high in occupancy by crystal structure analysis, was more stable. The phenylethyl part of fentanyl existed in several stable conformations.

Enhanced dissolution and skin permeation profiles of epalrestat with ß-cyclodextrin derivatives using a cogrinding method.

Epalrestat (EPL) is a water-insoluble drug (14µM) that inhibits aldose reductase. This study investigated the interactions between ß-cyclodextrin (CD) derivatives and EPL to determine the solubilizing effect on EPL from phase solubility diagrams. We improved the solubility of EPL in water by adding ß-CD derivatives. Moreover, the solubility of EPL mixed with ß-CD derivatives by cogrinding in a ball mill method was about 2-3 times higher than those of EPL with the same CD concentration (5mM) calculated from phase solubility diagrams. In addition, we investigated the effect of ß-CD derivatives on in vitro percutaneous absorption of EPL through hairless mouse skin. Among the coground mixtures of EPL and ß-CD derivatives, the mixture containing methyl (ME)-ß-CD showed the strongest enhancement of EPL skin permeation. Furthermore, adding 10wt% urea as a skin permeation enhancer after cogrinding with ME-ß-CD improved the flux of EPL 300 times compared to the flux of EPL alone. This result indicates the ME-ß-CD ground mixture system with urea has potential as a new transdermal drug delivery system of EPL for diabetic neuropathy.

Preparation and Evaluation of Modified Mohs Paste without Starch.

Mohs paste is an external preparation containing zinc hydrochloride and zinc oxide starch as the main ingredient, and it is used for the palliative treatment of patients with surgically untreatable malignant tumors. However, it has problems, such as changes in hardness and viscoelasticity with time and liquefaction by exudate. To overcome these problems, we modified the formulation of Mohs paste by excluding starch, which is the cause of physical changes, and investigated the base. In the modified Mohs paste using the macrogol ointment for the base, no marked change with time was noted in the hardness, malleability, or elongation property, and the water-absorbing properties were equivalent to those of Mohs paste immediately after preparation. The hardness did not decrease even after absorbing water. The drug release rate increased 1.5 times with the modified Mohs paste. Based on these findings, the risk of liquefaction-associated damage of the surrounding skin decreased on using the modified Mohs paste, and preparing in advance became possible. These results suggest that the modified Mohs paste using the macrogol ointment for the base exhibits an equivalent effect for control of exudate and a high effect for tissue fixation.