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We revisit our prior work on clock skew compensation immune to floating-point precision loss and provide practical as well as theoretical bounds on the initial value of the skew-compensated clock based on a systematic analysis of the errors of floating-point operations; by practical bounds, we mean the actual values of the theoretical bounds calculated at resource-constrained computing platforms like WSN nodes equipped with 32-bit single-precision floating-point format. Numerical examples demonstrate that the proposed practical bounds on single-precision floating-point format do not violate the theoretical bounds and thereby can guarantee the correctness of the clock skew compensation on resource-constrained computing platforms. [ABSTRACT FROM AUTHOR]

In a wireless sensor network (WSN), reducing the energy consumption of battery-powered sensor nodes is key to extending their operating duration before battery replacement is required. Message bundling can save on the energy consumption of sensor nodes by reducing the number of message transmissions. However, bundling a large number of messages could increase not only the end-to-end delays and message transmission intervals, but also the packet error rate (PER). End-to-end delays are critical in delay-sensitive applications, such as factory monitoring and disaster prevention. Message transmission intervals affect time synchronization accuracy when bundling includes synchronization messages, while an increased PER results in more message retransmissions and, thereby, consumes more energy. To address these issues, this paper proposes an optimal message bundling scheme based on an objective function for the total energy consumption of a WSN, which also takes into account the effects of packet retransmissions and, thereby, strikes the optimal balance between the number of bundled messages and the number of retransmissions given a link quality. The proposed optimal bundling is formulated as an integer nonlinear programming problem and solved using a self-adaptive global-best harmony search (SGHS) algorithm. The experimental results, based on the Cooja emulator of Contiki-NG, demonstrate that the proposed optimal bundling scheme saves up to 51.8% and 8.8% of the total energy consumption with respect to the baseline of no bundling and the state-of-the-art integer linear programming model, respectively. [ABSTRACT FROM AUTHOR]

Based on the reverse asymmetric time synchronization framework, we have proposed several schemes with a major focus on the energy efficiency and computational complexity of a large number of battery-powered, low-cost sensor nodes in wireless sensor networks (WSNs). To address the cumulative end-to-end synchronization error, we have also introduced an idea of compensating for the processing delays at packet-relaying gateways as an energy-efficient way of multi-hop extension of WSN time synchronization schemes. In this paper, we present a comprehensive analysis of the multi-hop extension of WSN time synchronization schemes based on packet-relaying gateways with the per-hop delay compensation and the results of extensive experiments for the energy-efficient time synchronization schemes based on the reverse asymmetric time synchronization framework together with the flooding time synchronization protocol as a representative of existing schemes. Experimental results based on a real testbed demonstrate that the multi-hop extension based on packet-relaying gateways with the per-hop delay compensation greatly improves the performance of time synchronization of all the schemes considered compared to the multi-hop extension based on the conventional time-translating gateways. [ABSTRACT FROM AUTHOR]

Node identification based on unique hardware features like clock skews has been considered an efficient technique in wireless sensor networks (WSNs). Spoofing attacks imitating unique hardware features, however, could significantly impair or break down conventional clock-skew-based node identification due to exposed clock information through broadcasting. To defend against Spoofing attacks, we propose a new node identification scheme called node identification against Spoofing attack (NISA). It utilizes the reverse time synchronization framework, where sensor nodes’ clock skews are estimated at the head of a WSN, and the spatially-correlated radio link information to achieve simultaneous node identification and attack detection. We further provide centralized and distributed NISA for covering both single-hop and multi-hop scenarios, the former of which employs a single-input and multiple-output convolutional neural network. With a real WSN testbed consisting of TelosB sensor nodes running TinyOS, we investigate the identifiability of clock skews under temperature and voltage variations and evaluate the performance of both centralized and distributed NISA. Experimental results demonstrate that both centralized and distributed NISA could provide accurate node identification and Spoofing attack detection. [ABSTRACT FROM AUTHOR]

Large-scale multi-building and multi-floor indoor localization has recently been the focus of intense research in indoor localization based on Wi-Fi fingerprinting. Although significant progress has been made in developing indoor localization algorithms, few studies are dedicated to the critical issues of using existing and constructing new Wi-Fi fingerprint databases, especially for large-scale multi-building and multi-floor indoor localization. In this paper, we first identify the challenges in using and constructing Wi-Fi fingerprint databases for large-scale multi-building and multi-floor indoor localization and then provide our recommendations for those challenges based on a case study of the UJIIndoorLoc database, which is the most popular publicly available Wi-Fi fingerprint multi-building and multi-floor database. Through the case study, we investigate its statistical characteristics with a focus on the three aspects of (1) the properties of detected wireless access points, (2) the number, distribution and quality of labels, and (3) the composition of the database records. We then identify potential issues and ways to address them using the UJIIndoorLoc database. Based on the results from the case study, we not only provide valuable insights on the use of existing databases but also give important directions for the design and construction of new databases for large-scale multi-building and multi-floor indoor localization in the future. [ABSTRACT FROM AUTHOR]

The ever-increasing number of WSN deployments based on a large number of battery-powered, low-cost sensor nodes, which are limited in their computing and power resources, puts the focus of WSN time synchronization research on three major aspects of accuracy, energy consumption, and computational complexity. In the literature, the latter two aspects haven’t received much attention compared to the accuracy of WSN time synchronization. Especially in multi-hop WSNs, intermediate gateway nodes are overloaded with tasks for not only relaying messages but also a variety of computations for their offspring nodes as well as themselves. Therefore, not only minimizing the energy consumption but also lowering the computational complexity while maintaining the synchronization accuracy is crucial to the design of time synchronization schemes for resource-constrained sensor nodes. In this paper, focusing on the three aspects of WSN time synchronization, we introduce a framework of reverse asymmetric time synchronization for resource-constrained multi-hop WSNs and propose a beaconless energy-efficient time synchronization scheme based on reverse one-way message dissemination. Experimental results with a WSN testbed based on TelosB motes running TinyOS demonstrate that the proposed scheme conserves up to 95% energy consumption compared to the flooding time synchronization protocol while achieving microsecond-level synchronization accuracy. [ABSTRACT FROM AUTHOR]

Location fingerprinting using Received Signal Strength Indicators (RSSIs) has become a popular technique for indoor localization due to its use of existing Wi-Fi infrastructure and Wi-Fi-enabled devices. Artificial intelligence/machine learning techniques such as Deep Neural Networks (DNNs) have been adopted to make location fingerprinting more accurate and reliable for large-scale indoor localization applications. However, the success of DNNs for indoor localization depends on the availability of a large amount of pre-processed and labeled data for training, the collection of which could be time-consuming in large-scale indoor environments and even challenging during a pandemic situation like COVID-19. To address these issues in data collection, we investigate multi-dimensional RSSI data augmentation based on the Multi-Output Gaussian Process (MOGP), which, unlike the Single-Output Gaussian Process (SOGP), can exploit the correlation among the RSSIs from multiple access points in a single floor, neighboring floors, or a single building by collectively processing them. The feasibility of MOGP-based multi-dimensional RSSI data augmentation is demonstrated through experiments using the hierarchical indoor localization model based on a Recurrent Neural Network (RNN)—i.e., one of the state-of-the-art multi-building and multi-floor localization models—and the publicly available UJIIndoorLoc multi-building and multi-floor indoor localization database. The RNN model trained with the UJIIndoorLoc database augmented with the augmentation mode of "by a single building", where an MOGP model is fitted based on the entire RSSI data of a building, outperforms the other two augmentation modes and results in the three-dimensional localization error of 8.42   m. [ABSTRACT FROM AUTHOR]

We report the results of our investigation on the use of deep neural networks (DNNs) for building/floor classification and floor-level location estimation based on Wi-Fi fingerprinting. We propose a new DNN architecture based on a stacked autoencoder for feature space dimension reduction and a feed-forward classifier for multi-label classification with arg max functions to convert multi-label classification results into multi-class classification ones. We also demonstrate a prototype system for floor-level location estimation using received signal strengths measured on XJTLU campus. Our results show the strengths of DNN-based approaches, providing near state-of-the-art performance with less parameter tuning and higher scalability. [ABSTRACT FROM AUTHOR]

The chemical stability of 1-palmitoyl-2-linoleoyl-3-acetyl- rac -glycerol (PLAG), a therapeutic agent for neutropenia, was investigated using a validated stability-indicating reversed phase high-performance liquid chromatographic (RP-HPLC) method. The forced degradation of PLAG was carried out under the stress conditions of hydrolysis (alkaline, acidic and various pH buffers), oxidation, photolysis and heat. A simple, sensitive, specific, robust, precise and accurate RP-HPLC method was developed and validated for evaluating the degradation kinetics of PLAG. The chromatographic validation of various parameters, such as system suitability, detection limit, quantification limit, linearity, accuracy, precision, specificity, robustness and stability, was achieved. The method was validated for linearity, accuracy and precision over the concentration range of 0.7813–100 μg/mL ( r 2 = 0.9999). The proposed method provided excellent stability study of PLAG indicated by the resolution of degradation products from the drug. Degradation of PLAG provided first order kinetics under all experimental conditions. PLAG was catalysed more rapidly in alkaline and acidic conditions than in neutral conditions. PLAG was relatively stable in photolytic and oxidative conditions compared to hydrolysis and thermal conditions, although this drug was not also stable in these conditions. Exposed to high temperature, PLAG was more rapidly catalysed. The activation energy evaluated from the Arrhenius plot was about 110 kJ/mol in the thermal conditions. Additionally, PLAG with a t 1/2 of about 400 h was very stable at room temperature. Therefore, PLAG was considerably influenced by alkaline and acidic hydrolysis, and thermal degradation. [ABSTRACT FROM AUTHOR]

In the past decade, the self-immolative biodegradable polymer arose as a novel paradigm for its efficient degradation mechanism and vast potential for advanced biomedical applications. This study reports successful synthesis of a novel biodegradable polymer capable of self-immolative backbone cleavage. The monomer is designed by covalent conjugations of both pendant redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), which serves as the structural backbone. The polymerization of the monomer with hexamethylene diisocyanate yields a linear redox-sensitive polymer that can systemically degrade via sequential 1,6-elimination and 1,5-cyclization reactions within an effective timeframe. Ultimately, the polymer's potential for biomedical application is simulated through in vitro redox-triggered release of paclitaxel from polymeric nanoparticles. [ABSTRACT FROM AUTHOR]

We consider energy-efficient time synchronization in a wireless sensor network where a head node is equipped with a powerful processor and supplied power from outlet, and sensor nodes are limited in processing and battery-powered. It is this asymmetry that our study focuses on; unlike most existing schemes to save the power of all network nodes, we concentrate on battery-powered sensor nodes in minimizing energy consumption for time synchronization. We present a time synchronization scheme based on asynchronous source clock frequency recovery and reverse two-way message exchanges combined with measurement data report messages, where we minimize the number of message transmissions from sensor nodes while achieving sub-microsecond time synchronization accuracy through propagation delay compensation. We carry out the performance analysis of the estimation of both measurement time and clock frequency with lower bounds for the latter. Simulation results verify that the proposed scheme outperforms the schemes based on conventional two-way message exchanges with and without clock frequency recovery in terms of the accuracy of measurement time estimation and the number of message transmissions and receptions at sensor nodes as an indirect measure of energy efficiency. [ABSTRACT FROM PUBLISHER]

To develop a novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for a water-insoluble oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) with improved stability and oral bioavailability, numerous S-SNEDDS were prepared with surfactant, hydrophilic polymer, antioxidant, and calcium silicate (porous carrier) using the spray-drying method. Their physicochemical properties were evaluated using emulsion droplet size analysis, SEM and PXRD. Moreover, the solubility, dissolution, stability, and pharmacokinetics of the selected S-SNEDDS were assessed compared with the drug and a commercial soft capsule. Sodium lauryl sulfate (SLS) and hydroxypropyl methylcellulose (HPMC) with the highest drug solubility were selected as surfactant and hydrophilic polymer, respectively. Among the antioxidants tested, only butylated hydroxyanisole (BHA) could completely protect the drug from oxidative degradation. The S-SNEDDS composed of PLAG/SLS/HPMC/BHA/calcium silicate at a weight ratio of 1: 0.25: 0.1: 0.0002: 0.5 provided an emulsion droplet size of less than 300 nm. In this S-SNEDDS, the drug and other ingredients might exist in the pores of carrier and attach onto its surface. It considerably improved the drug stability (about 100 vs. 70%, 60 °C for 5 d) and dissolution (about 80 vs. 20% in 60 min) compared to the commercial soft capsule. Moreover, the S-SNEDDS gave higher AUC, Cmax, and Tmaxvalues than the commercial soft capsule; in particular, the former improved the oral bioavailability of PLAG by about 3-fold. Our results suggested that this S-SNEDDS provided excellent stability and oral bioavailability of PLAG. Thus, this S-SNEDDS would be recommended as a powerful oral drug delivery system for an oily drug, PLAG. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a novel prasugrel base microsphere-loaded tablet (PBMST) with enhanced stability as a bioequivalent to the commercial prasugrel hydrochloride-loaded tablet. Numerous prasugrel base-loaded microspheres were prepared with hydroxypropylmethyl cellulose (HPMC), colloidal silica and various acidifying agents using a spray-drying process, and the physicochemical properties, solubility and stability were investigated. The PBMSTs were prepared and their dissolution, pharmacokinetics in beagle dogs and stability were evaluated compared to commercial prasugrel hydrochloride-loaded tablets. Among the acidifying agents tested, phosphoric acid provided the greatest increase in drug solubility, by as much as 110-fold. The prasugrel base-loaded microspheres composed of prasugrel base, HPMC, colloidal silica and phosphoric acid at a weight ratio of 10/10/5/2.5 provided an amorphous drug and reduced particle size of about 11.3 μm. Moreover, it exhibited excellent solubility and improved stability compared to prasugrel base and hydrochloride. Moreover, PBMST drug dissolution was improved in comparison to the prasugrel base-loaded tablet (PBT), with similar dissolution to the commercial prasugrel hydrochloride-loaded tablet at pH 1.2 and 4.0. PBMST provided significantly higher plasma concentrations of AUC and C max in beagle dogs compared to PBT. In particular, the AUC of PBMST was approximately four times greater than PBT, leading to improved oral bioavailability. There were no significant differences observed for all pharmacokinetic parameters between PBMST and the commercial prasugrel hydrochloride-loaded tablet, suggesting their bioequivalence in beagle dogs. Furthermore, the prepared PBMSTs were stable for at least six months. Therefore, this novel prasugrel base microsphere-loaded tablet could be a potential alternative for enhancing the stability and bioavailability of prasugrel. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop HM30181 mesylate salt (HM30181M)-loaded microcapsules as a novel P-glycoprotein inhibitor for enhancing the oral absorption of paclitaxel. The effect of various carriers including hydrophilic polymers and solvents on the solubility of HM30181M were evaluated. Among the hydrophilic polymers and solvents tested, HPMC and methylene chloride (and ethanol) provided the highest HM30181M solubility. Numerous HM30181M-loaded microcapsules were prepared with HPMC, silicon dioxide and acidifying agents using a spray-drying technique, and their solubility, dissolution and physicochemical properties were evaluated. Furthermore, a pharmacokinetic study was performed after oral administration of paclitaxel alone, simultaneously with HM30181M powder or HM30181M-loaded microcapsules to rats. Among the acidifying agents investigated, phosphoric acid provided the best improvement in the solubility and dissolution of HM30181M. Moreover, the microcapsule composed of HM30181M, HPMC, silicon dioxide and phosphoric acid at a weight ratio of 3:6:3:2 remarkably enhanced the solubility and dissolution of HM30181M compared with the HM30181M powder alone. The microcapsules were spherical in shape, had a reduced particle size of about 7 μm, and contained HM30181M in an amorphous state. Furthermore, this microcapsule significantly enhanced HM30181M absorption, making it about 1.7-fold faster and 1.6-fold greater after simultaneous administration, leading to about 70- and 2-fold improved oral bioavailability of paclitaxel compared with paclitaxel alone and the simultaneous administration with HM30181M powder, respectively. Thus, this novel microcapsule could be a potential candidate for effective P-glycoprotein inhibition during oral administration of paclitaxel. [ABSTRACT FROM AUTHOR]

To develop a novel sodium fusidate-loaded triple polymer hydrogel dressing (TPHD), numerious polyvinyl alcohol-based (PVA) hydrogel dressings were prepared with various hydrophilic polymers using the freeze-thaw method, and their hydrogel dressing properties were assessed. Among the hydrophilic polymers tested, sodium alginate (SA) improved the swelling capacity the most, and polyvinyl pyrrolidone (PVP) provided the greatest improvement in bioadhesive stength and mechanical properties. Thus, PVA based-TPHDs were prepared using different ratios of PVP:SA. The effect of selected PVP:SA ratios on the swelling capacity, bioadhesive strength, mechanical properties, and drug release, permeation and deposition characteristics of sodium fusidate-loaded PVA-based TPHDs were assessed. As the ratio of PVP:SA increased in PVA-loaded TPHD, the swelling capacity, mechanical properties, drug release, permeation and deposition were improved. The TPHD containing PVA, PVP, SA and sodium fusidate at the weight ratio of 10/6/1/1 showed excellent hydrogel dressing properties, release, permeation and deposition of drug. Within 24 h, 71.8 ± 1.3% of drug was released. It permeated 625.1 ± 81.2 μg/cm 2 through the skin and deposited of 313.8 ± 24.1 μg/cm 2 within 24 h. The results of in vivo pharmacodynamic studies showed that sodium fusidate-loaded TPHD was more effective in improving the repair process than was a commercial product. Thus, this sodium fusidate-loaded TPHD could be a novel tool in wound care. [ABSTRACT FROM AUTHOR]

A comprehensive research framework for a comparative analysis of candidate network architectures and protocols in the clean-slate design of next-generation optical access is proposed. The proposed research framework consists of a comparative analysis framework based on multivariate non-inferiority testing and a notion of equivalent circuit rate taking into account user-perceived performances and a virtual test bed providing a complete experimental platform for the comparative analysis. The capability of the research framework is demonstrated through numerical results from the study of the elasticity of hybrid time division multiplexing/wavelength division multiplexing–passive optical network based on tunable transceivers. [ABSTRACT FROM PUBLISHER]

Features a study which considered the issue of source clock frequency recovery (SCFR) in packet networks and proposed an adaptive clock method based on the Kalman filter (KF) with low-pass filtering, Kalman filter-based Adaptive clock method with Low-pass prefiltering (KALP). KALP algorithm; Comparative study of SCFR performances between KALP scheme and buffer-based adaptive clock method.

Most of the current formulations of the optimal scheduling of appliance energy consumption use the vectors of appliances' scheduled energy consumption over equally divided time slots of a day as optimization variables, which does not take into account the atomicity of certain appliances' operations, i.e., the non-interruptibility of appliances' operations and the non-throttleability of the energy consumption patterns specific to their operations. In this paper, we provide a new formulation of atomic scheduling of energy consumption based on the optimal routing framework; the flow configurations of users over multiple paths between the common source and destination nodes of a ring network are used as optimization variables, which indicate the starting times of scheduled energy consumption, and optimal scheduling problems are now formulated in terms of the user flow configurations. Because the atomic optimal scheduling results in a Boolean-convex problem for a convex objective function, we propose a successive convex relaxation technique for efficient calculation of an approximate solution, where we iteratively drop fractional-valued elements and apply convex relaxation to the resulting problem until we find a feasible suboptimal solution. Numerical results for the cost and peak-to-average ratio minimization problems demonstrate that the successive convex relaxation technique can provide solutions close to and often identical to global optimal solutions. [ABSTRACT FROM AUTHOR]

Energy efficiency and end-to-end delay are two of the major requirements for the monitoring and detection applications based on resource-constrained wireless sensor networks (WSNs). As new advanced technologies for accurate monitoring and detection—such as device-free wireless sensing schemes for human activity and gesture recognition—have been developed, time synchronization accuracy becomes an important requirement for those WSN applications too. Message bundling is considered one of the effective methods to reduce the energy consumption for message transmissions in WSNs, but bundling more messages increases the transmission interval of bundled messages and thereby their end-to-end delays; the end-to-end delays need to be maintained within a certain value for time-sensitive applications like factory monitoring and disaster prevention, while the message transmission interval affects time synchronization accuracy when the bundling includes synchronization messages as well. Taking as an example a novel WSN time synchronization scheme recently proposed for energy efficiency, we investigate an optimal approach for message bundling to reduce the number of message transmissions while maintaining the user-defined requirements on end-to-end delay and time synchronization accuracy. Formulating the optimal message bundling problem as integer linear programming, we compute a set of optimal bundling numbers for the sensor nodes to constrain their link-level delays, thereby achieving and maintaining the required end-to-end delay and synchronization accuracy. Extensive experimental results based on a real WSN testbed using TelosB sensor nodes demonstrate that the proposed optimal bundling could reduce the number of message transmissions about 70% while simultaneously maintaining the required end-to-end delay and time synchronization accuracy. [ABSTRACT FROM AUTHOR]

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development. [ABSTRACT FROM AUTHOR]

This study aimed to isolate the proteolytic fraction from the silkworm thorn fruit (Cudrania tricuspidata) through ethanol precipitation at different ratios, and to determine its proteolytic activity and optimal activity conditions. Furthermore, the hydrolysis characteristics and antioxidant activity of soy protein isolate (SPI) and whey protein concentrate (WPC) hydrolyzates obtained through the enzymatic hydrolysis of freeze-dried silkworm thorn fruit powder (SF) were evaluated. For isolation and partial purification of proteolytic fraction, the water-solubilized fraction of the silkworm thorn fruit was purified through ethanol precipitation at four different ratios of 1:1, 1:2, 1:4, and 1:6 (v/v). The protein recovery rate, caseinolytic activity, protein pattern, and optimal activity (pH, temperature, and inhibitors) of fractional ethanol precipitate obtained from the silkworm thorn fruit (ESF) were evaluated. The proteolytic fraction obtained from silkworm thorn fruit exhibited a major protein band around 65–70 kDa and showed the highest proteolytic activity at a 1:4 ratio of ethanol precipitation (p < 0.05). The optimal activity of the measured enzyme fraction was determined to be at pH 9.0 and 50 °C, and the proteolytic activity of ESF was almost inhibited by phenyl methyl sulphonyl fluoride (PMSF, 2 mM), a serine protease inhibitor. Compared to Alcalase and papain, extensively used as commercial enzymes, the silkworm thorn fruit powder was less effective in hydrolyzing SPI and WPC. Nevertheless, SPI and WPC hydrolyzates mediated with silkworm thorn fruit powder showed even better antioxidant activities than those mediated with Alcalase and papain. Thus, our results show the potential application of silkworm thorn fruit as a novel source of plant protease for producing human-grade protein hydrolyzates. [ABSTRACT FROM AUTHOR]

The purpose of this study is to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral absorption of poorly water-soluble enzalutamide (ENZ). Considering the rapid recrystallization of the drug, based on solubility and crystallization tests in various oils, surfactants and co-surfactants, Labrafac PG 10%, Solutol HS15 80%, and Transcutol P 10%, which showed the most stable particle size and polydispersity index (PDI) without drug precipitation, were selected as the optimal SNEDDS formulation. The optimized SNEDDS formulation showed excellent dissolution profiles for all the drugs released at 10 min of dissolution due to the increased surface area with a small particle size of approximately 16 nm. Additionally, it was confirmed to be stable without significant differences in physical and chemical properties for 6 months under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) and stressed conditions (60 ± 2 °C). Associated with the high dissolutions of ENZ, pharmacokinetic parameters were also greatly improved. Specifically, the AUC was 1.9 times higher and the Cmax was 1.8 times higher than those of commercial products (Xtandi® soft capsule), resulting in improved oral absorption. Taken together with the results mentioned above, the SNEDDS could be an effective tool as a formulation for ENZ and other similar drugs. [ABSTRACT FROM AUTHOR]

Pet owners think of their animals as part of their family, which further promotes the growth of the pet food market, encouraging pet owners to select nutritious, palatable, and high-quality foods for pets. Therefore, the evaluation of taste and volatile compounds in pet foods is essential to improve palatability. In this study, the sensory characteristics of taste and odor compounds in 10 commercially available dry dog foods were investigated using electronic tongue (E-tongue), electronic nose (E-nose), gas chromatography–mass spectrometry (GC-MS), and gas chromatography–olfactometry (GC-O). Dry dog foods were separated based on the sensory properties of taste and volatile compounds through the multivariate analysis of integrated results of the E-tongue and E-nose. A total of 67 odor active compounds were detected through GC-MS and GC-O, and octanal, nonanal, 2-pentyl furan, heptanal, and benzaldehyde were identified as key odor compounds which may have positive effects on food intake. The multivariate analysis was used to classify samples based on key odor compounds. Volatile compounds responsible for aroma properties of samples were evaluated using GC-O and multivariate analysis in this present study for the first time. These results are expected to provide fundamental data for sensory evaluation in producing new dog foods with improved palatability. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the effect of d -α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on the physicochemical characterization and oral bioavailability of a novel l -sulpiride-loaded quaternary microcapsule (QMC). The effect of carriers on drug solubility was investigated. Among the carriers tested, polyvinyl pyrrolidone (PVP), sodium lauryl sulphate (SLS) and TPGS were selected as polymer, surfactant and absorption enhancer, respectively, due to their high drug solubility. Using the solvent evaporation method, numerous QMCs with different ratios of l -sulpiride, PVP, SLS and TPGS were prepared, and their physicochemical properties, solubility and release were evaluated. In addition, the influence of TPGS concentration on the oral bioavailability of various drug doses was evaluated. All QMCs converted the crystalline drug to the amorphous form and remarkably improved the solubility, release and oral bioavailability of the drug. Furthermore, the TPGS concentration in the QMCs hardly affected the crystallinity, particle size and release, but considerably increased the solubility and oral bioavailability of the drug. In particular, as the dose of administered drug was increased, TPGS provided a greater improvement in oral drug bioavailability. Thus, TPGS played an important role in improving the oral bioavailability of l -sulpiride. Moreover, the QMC with a drug/PVP/SLS/TPGS weight ratio of 5:12:1 :20 with approximately 3.3-fold improved oral bioavailability would be recommended as a commercial pharmaceutical product for oral administration of l -sulpiride. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the influence of different hydrophilic polymers on the swelling, bioadhesion and mechanical strength of hydrocolloid wound dressings (HCDs) in order to provide an appropriate composition for a hydrocolloid wound dressing system. In this study, the HCDs were prepared with styrene-isoprene-styrene copolymer (SIS) and polyisobutylene (PIB) as the base using a hot melting method. Additionally, numerous SIS/PIB-based HCDs were prepared with six hydrophilic polymers, and their wound dressing properties were assessed. Finally, the wound healing efficacy of the selected formulations was compared to a commercial wound dressing. The swelling ratio, bioadhesive force and mechanical strengths of HCDs were increased in the order of sodium alginate > sodium CMC = poloxamer = HPMC > PVA = PVP, sodium alginate > sodium CMC = poloxamer > PVA> HPMC = PVP and sodium alginate ≥ PVA >PVP = HPMC = sodium CMC > poloxamer, respectively. Among the hydrophilic polymers tested, sodium alginate most enhanced the swelling capacity, bioadhesive force and mechanical strengths. Thus, the hydrophilic polymers played great role in the swelling, bioadhesion and mechanical strength of SIS/PIB-based HCDs. The HCD formulation composed of PIB, SIS, liquid paraffin and sodium alginate at the weight ratio of 20/25/12/43 gave better wound dressing properties and more excellent wound healing efficacy than the commercial wound dressing. Therefore, the novel HCD formulation could be a promising hydrocolloid system for wound dressings. [ABSTRACT FROM AUTHOR]

Abstract: Ability of any formulation to keep the drug in solubilized form in vivo is essential for bioavailability (BA) enhancement rather than the solubility of drug in the formulation vehicle/matrix itself. Besides, utilization of an excess amount of surfactants/co-surfactants to solubilize the drug in the lipid formulation poses potential pharmaceutical as well as health problems. To address this problem, self-emulsifying phospholipid suspension (SEPS) consisting of high amount of phospholipid (an endogenous lipid with efficient in vivo emulsification capability) and relatively low amount of surfactant/co-surfactant has been proposed to enhance the bioavailability (BA) of lutein. In this study, the ability of SEPS formulation to enhance the BA of lutein was assessed from three SEPS formulations with various amounts of phospholipid (SEPS-0, SEPS-I, and SEPS-II with 0mg, 250mg, and 500mg of Phosal® 53 MCT, respectively) in beagle dogs following a single oral administration of lutein equivalent to 100mg, and were compared with commercial formulation (CF). In addition, the retinal accumulation of lutein in Sprague Dawley (SD) rats’ eyes from SEPS-II formulation (lutein dose of 100mg/kg/day) was investigated following single daily oral administration for a period of 14 days. CF and placebo (vegetable oil without lutein) were also administered for the same period of time and were compared with the SEPS-II formulation. In the relative BA study in beagle dogs, no significant differences were observed between the pharmacokinetic (PK) parameters of formulation SEPS-O and CF. However, the C max in comparison to CF was 3.70 folds and 11.76 folds higher for SEPS-I and SEPS-II, respectively. Relative BA compared to CF was 178.88% and 473.13% for SEPS-I and SEPS-II, respectively. The retinal lutein accumulation was 0.91±0.31ng/g, 3.45±1.63ng/g, and 14.72±2.02ng/g for placebo, CF, and SEPS-II, respectively. This enhancement was about 16.1 folds and 4.27 folds compared to placebo and CF, respectively. The relative BA study in dogs and retinal accumulation study in rats demonstrated the excellent ability of SEPS to enhance the BA of lutein. For this reason, SEPS containing lutein could be a promising lipid based delivery system for the prevention of ocular diseases. [Copyright &y& Elsevier]

Decidualization of the endometrial stroma is an essential differentiation process for embryo implantation and maintenance of pregnancy. We previously reported that protein phosphatase 2A (PP2A) acts as a key mediator during cAMP‐induced decidualization of human endometrial stromal cells (hESCs). However, the mechanism underlying its activation has remained obscure in hESCs. In the present study, we aimed to reveal the mechanism that induces the nitration of PP2A catalytic subunit (PP2Ac) during cAMP‐induced decidualization of hESCs. First, cAMP‐induced PP2Ac nitration was significantly repressed using L‐NAME, an inhibitor of nitric oxide synthase (NOS). Among several NOS isoforms, only inducible NOS (iNOS) was highly expressed in hESCs, indicating that iNOS directly induces the nitration of PP2Ac. Second, cAMP‐induced iNOS expression and PP2Ac nitration were decreased by treatment with TSA, an inhibitor of histone deacetylase 5 (HDAC5). cAMP‐induced phosphorylation of CaMKII and HDAC5 was suppressed by treatment with U73122 (an inhibitor of phospholipase C) or transfection of PLCε siRNA. Finally, small G protein Rap1 and its guanine nucleotide exchange factor Epac1 were found to be involved in cAMP‐induced PP2A activation. Taken together, our results suggest that PP2Ac nitration during cAMP‐induced decidualization of hESCs is induced through the Epac1‐Rap1‐PLCε‐CaMKII‐HDAC5‐iNOS signaling pathway. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a novel d‐cycloserine tablet with improved stability and dissolution equivalent to the d‐cycloserine‐loaded commercial hard capsule. The effect of alkalizing agents on the d‐cycloserine was investigated. Numerous d‐cycloserine tablets were prepared with various calcium hydroxide contents, using direct or wet granulation compression, and their stability and dissolution were assessed compared to the commercial d‐cycloserine‐loaded hard capsule. Long‐term stability of the selected d‐cycloserine tablet in aluminum polyvinylchloride blister were conducted at 25 °C/60% RH or 40 °C/75% RH for 6 months. Amongst the stabilizers tested, calcium hydroxide gave the best stability at 60 °C/75% RH for 2 days due to its alkaline and waterproofing properties. Calcium hydroxide hardly affected dissolution of drug from the tablets but considerably increased stability of drug in the tablets. Particularly, the tablet prepared with d‐cycloserine, calcium hydroxide, polyvinylpyrrolidone, and talc in the weight ratio of 250/250/40/7.5 using direct compression gave similar dissolution but significantly improved stability compared to the commercial hard capsule. This tablet, packaged in aluminum polyvinylchloride blister, was stable in the above accelerated conditions for 6 months. Therefore, this novel d‐cycloserine tablet with enhanced stability and dissolution equivalent to the commercial hard capsule would be recommended as an alternative. [ABSTRACT FROM AUTHOR]

The purpose of this study was to improve the chemical stability of D‐cycloserine via tablet form containing an alkali stabilizer. The influence of alkalizing agents on the stability of D‐cycloserine was investigated at 60 °C/75% RH for 2 days. The drug stability was evaluated with the D‐cycloserine‐loaded tablets prepared with various amounts of magnesium oxide using direct compression method. Compared to D‐cycloserine powder and a commercial D‐cycloserine‐loaded product, the long‐term drug stability on the chosen tablet was assessed at 40, 60, and 40 °C/75% RH during 6 months. Amongst the stabilizers investigated, magnesium oxide most improved the stability of D‐cycloserine at the accelerated stress condition. The magnesium oxide/drug ratio of 1 and 2 showed higher remaining drug concentrations than those less than 0.5; however, two formers gave no significant difference in the remaining drug concentrations. Amongst the tablets tested, the formulation composed of D‐cycloserine, magnesium oxide, and talc at the weight ratio of 250/250/5 most increased the stability of D‐cycloserine. Additionally, due to the alkali and water‐proofing property of magnesium oxide, this tablet improved the stability of D‐cycloserine compared to the drug powder and commercial product. Hence, this novel tablet with enhanced drug stability would be a candidate for oral pharmaceutical product of D‐cycloserine. [ABSTRACT FROM AUTHOR]

SN-38 (7-ethyl-10-hydroxy-camptothecin) is an active metabolite of irinotecan (CPT-11) and the most potent camptothecin analogue. In this study, 2,4-dinitrobenzene sulfonyl (DNS) was covalently conjugated as a GSH-sensitive trigger to 10’–OH of SN-38 to yield a GSH-sensitive prodrug, denoted as DNS-SN38, with virtually quenched fluorescence due to donor-excited photo-induced electron transfer (d-PeT). By investigating DNS-SN38's activation properties upon fluorescence restoration and cytotoxic potency against ovarian cancer cell lines (A2780 and m-Cherry + OCSC1-F2), its potential applicability as a useful chemotherapeutic agent was demonstrated. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a novel dabigatran etexilate hemisuccinate (DEH) salt-loaded polycap with bioequivalence to the dabigatran etexilate mesylate (DEM)-loaded commercial product. DEH prepared with dabigatran etexilate base (DE) and succinic acid was less hygroscopic but less soluble than DEM. Numerous micronized DEHs and DEH-loaded solid dispersions were prepared employing the spiral jet-milling and spray-drying techniques, respectively. Among the formulations prepared, a micronized DEH prepared with the injection air at 1.5 bar and the grinding air at 2 bar, and a DEH-loaded solid dispersion prepared with 6 g HPMC most improved the drug solubility, respectively. Moreover, the micronized DEH provided more increased drug solubility and dissolution compared with the solid dispersion, even though its drug solubility was still lower than that of DEM. Unlike the situation in other studies, the enhanced solubility and dissolution of DEH was more due to particle size reduction than to a change to the amorphous form. The micronized DEH prepared with Myrj 52S had greater drug solubility than preparations with other surfactants. Among the organic acids investigated, only fumaric acid (128.8 mg) showed a similar pattern in pH changes to the DEM-loaded commercial product. Furthermore, in order to make the environment acidic while preventing the direct contact of the drug with fumaric acid, the polycap was composed of a tablet containing the micronized DEH, Myrj 52S and other ingredients, and separate fumaric acid. This micronized DEH-loaded polycap was dissolution- and bio-equivalent to the DEM-loaded commercial product in beagle dogs. Thus, the novel micronized DEH-loaded polycap would be a promising alternative to the DEM-loaded commercial product. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the powder properties, solubility, dissolution and oral absorption of solvent–wetted (SWSD) and kneaded (KNSD) l -sulpiride–loaded solid dispersions. The SWSD and KNSD were prepared with silicon dioxide, sodium laurylsulfate and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) using a spray dryer and high shear mixer, respectively. Their powder properties, solubility, dissolution and oral absorption were assessed compared to l -sulpiride powder. The drug in SWSD was in the amorphous state; however, in KNSD, it existed in the crystalline state. The SWSD with a drug/sodium laurylsulphate/TPGS/silicon dioxide ratio of 5/1/2/12 gave the higher drug solubility and dissolution compared to the KNSD with the same composition. The oral absorption of drug in the SWSD was 1.4 fold higher than the KNSD and 3.0 fold higher than the l -sulpiride powder ( p < 0.05) owing to better solubility and reduced crystallinity. Furthermore, the SWSD at the half dose was bioequivalent of commercial l -sulpiride–loaded product in rats. Thus, the SWSD with more improved oral absorption would be recommended as an alternative for the l -sulpiride–loaded oral administration. [ABSTRACT FROM AUTHOR]

Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na-CMC)/sodium lauryl sulfate (SLS) at 3/0.5/0.5 (w/w) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and Cmax were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTX-loaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability. [ABSTRACT FROM AUTHOR]