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The article discusses the rapid evolution of artificial intelligence (AI) and related innovative technologies in clinical pharmacy practice and education. It highlights the potential benefits of AI in enhancing patient care, optimizing therapeutic outcomes, and advancing research. The use of machine learning in clinical decision support systems, drug discovery, and medication adherence is explored. The article also mentions the emergence of large language models (LLM) and their potential applications in clinical pharmacy. Ethical considerations, such as data privacy and algorithmic bias, are emphasized. The International Journal of Clinical Pharmacy is calling for submissions on AI-based solutions and other innovative technologies in clinical pharmacy practice and research to promote excellence and better equip pharmacy practitioners. [Extracted from the article]

The future of innovative robotic technologies and artificial intelligence (AI) in pharmacy and medicine is promising, with the potential to revolutionize various aspects of health care. These advances aim to increase efficiency, improve patient outcomes, and reduce costs while addressing pressing challenges such as personalized medicine and the need for more effective therapies. This review examines the major advances in robotics and AI in the pharmaceutical and medical fields, analyzing the advantages, obstacles, and potential implications for future health care. In addition, prominent organizations and research institutions leading the way in these technological advancements are highlighted, showcasing their pioneering efforts in creating and utilizing state-of-the-art robotic solutions in pharmacy and medicine. By thoroughly analyzing the current state of robotic technologies in health care and exploring the possibilities for further progress, this work aims to provide readers with a comprehensive understanding of the transformative power of robotics and AI in the evolution of the healthcare sector. Striking a balance between embracing technology and preserving the human touch, investing in R&D, and establishing regulatory frameworks within ethical guidelines will shape a future for robotics and AI systems. The future of pharmacy and medicine is in the seamless integration of robotics and AI systems to benefit patients and healthcare providers. [ABSTRACT FROM AUTHOR]

Hospital pharmacy managers make inventory decisions for thousands of different perishable drugs. Commonly, these managers do not have the resources to implement advanced mathematical models. Closed-form solutions are attractive because they provide the inventory policy quickly and are easy to implement. However, when deriving these solutions, one must consider that pharmaceutical supply chains experience disruptions. We first derive closed-form solutions for a non-perishable lost-sales (R,S) periodic review inventory system with supply chain disruptions. We then extend the solutions to incorporate perishability and apply the solutions to a hospital pharmacy inventory system. We find that (i) it is important to account for perishability and supply chain disruptions simultaneously as only accounting for supply chain disruptions increases both drug shortages [possible 65% increase] and waste [possible waste equivalent to 50% of the daily demand], (ii) it is critical to consider the duration of and time between supply chain disruptions, (iii) the expected number of shortages is insensitive to changes in the standard deviation when demand is normally distributed, but for short expiration lifetimes, the expected number wasted increases linearly as the standard deviation of demand increases, and (iv) not accurately depicting the supply chain disruption process can triple the number of shortages. [ABSTRACT FROM AUTHOR]

Community pharmacies have made significant advances in digital technology; however, mobile systems are only emerging in this sector and mostly focusing patient-centric connections. This study reveals a case of digital transformation in a mobile connected pharmacy, balancing efficient pharmaceutical services and digital innovation. A mobile connected pharmacy solution (mPharmaCare) is developed for a community of near 100.000. The first stage includes a bibliometric analysis and a structured literature review of the mobile connected pharmacy. In the second stage, action research was conducted to evaluate mPharmaCare adoption. A dual organizational structure was tested to cope with innovation and efficient exploration of pharmacy services. Community Pharmacy 5.0 is an inspiring vision that will take advantage of mobility. However, there are tensions between the core pharmacy business and the new technology layers of community connections. Community pharmacies require both client-centric and community-centric approaches to achieve individualization of patient care and horizontal and end-to-end digital integration of pharmacy data. Digital transformation can remove silos in the community pharmacy. Creating an - internal or outsourced - innovation division may be suitable for medium and large community pharmacies. Moreover, pharmacies must consider shifting to a product-service system offer, deploying synchronization mechanisms with different stakeholders. [ABSTRACT FROM AUTHOR]

Aim: To evaluate in a laboratory study, the effect of different canal irrigant solutions and activation techniques on transforming growth factor (TGF‐β1), insulin growth factor‐1 (IGF‐1), bone morphogenetic protein‐7 (BMP‐7) and vascular endothelial growth factor‐A (VEGF‐A) release levels from the dentine of extracted premolar teeth. Methodology: Seventy premolar teeth with single root and canal were used. The lengths of the root segments were standardized to 12 mm, and the root canals were prepared up to size 100 with hand files. All surfaces of the teeth were covered with nail polish except the inner root canal surface. The root canals were irrigated with 1.5% NaOCl. Ten teeth were allocated to the control group. The remaining sixty teeth were divided into 2 main groups according to the chelating agent used (17% EDTA, 10% Citric acid; CA) and 3 subgroups (n = 10) according to irrigation activation technique (conventional syringe irrigation (CSI), passive ultrasonic irrigation (PUI) and Er:YAG laser activation). After the activation procedure, the root segments were placed into eppendorf tubes containing 1 mL of phosphate‐buffered saline solution and kept at 37℃. TGF‐β1, IGF‐1, BMP‐7 and VEGF‐A release levels from dentine were measured using the enzyme‐linked immunosorbent assay (ELISA) method at 24 h and at day 7. The volume of root canals was calculated using cone‐beam computed tomography. The growth factor levels were calculated in ng/mL except VEGF‐A (pg/ml). Normality analysis of the data was evaluated with the Kolmogorov–Smirnov test. Statistical analysis was performed using the Mann–Whitney‐U and Wilcoxon tests. Results: Regardless of the activation type and sampling time, EDTA caused significantly more IGF release than did CA, whereas EDTA and CA were equally effective for the release of the other growth factors. For either EDTA or CA, the lowest and highest growth factor release levels were observed in the CSI and Er:YAG laser groups, respectively (p <.05). All of the growth factors were released significantly more at 24 h than on day 7 (p <.05). Conclusions: Irrigation activation techniques with EDTA or CA increased the release levels of all growth factors from the dentine of canal walls in extracted premolar teeth. [ABSTRACT FROM AUTHOR]

The investigators of the present study have identified Georgia as an area that could potentially have spatial equity issues with pharmacy deserts in rural areas and small cities. However, limited studies have been conducted for spatial equity of pharmacies in Georgia. Fewer studies have investigated these phenomena at the state level, and few have performed spatial correlations. Spatial equity refers to the idea that people should have equal or near-equal access to certain services (Hu et al., 2019). To fill in the gap of the literature and aid in forming solutions to pharmacy deserts in Georgia, the present study analyzed geographical patterns of spatial equity of pharmacy. Because large portions of Georgia are rural, such an analysis will elucidate how spatial equity affects such rural communities. Correlational analyses, logical regressions, and spatial analyses using Geographic Information Systems (GIS) were performed to understand the relationship between variables such as race, income level, poverty rate, and the total number of pharmacies. The study applied spatial autocorrelation and cluster analyses in ArcGIS, and statistical correlational analyses, and logical regressions in SPSS. Furthermore, the study used the 5-year (2014-2018) American Community Survey (ACS) database. At the county level, the results showed that a dense population, high median family income, and low poverty rate--among other variables--correlated with more pharmacies. In particular, total population (r(148) = .95) and population density (r(148) = .83) had a strong, positive relationship with the number of pharmacies in each county. Furthermore, the county level logical regression showed that total population and poverty rate significantly predict the number of pharmacies in each county, F(2, 146) = 648.91, P < .001, R2 = .95. At the census tract level, a low unemployment rate, high percentage of Hispanic Americans, and high median family income--among other variables--were associated with more pharmacies. In particular, total population (r(1967) = .28) had the strongest positive relationship with the number of pharmacies in each census tract. GIS global spatial autocorrelation and high-low cluster analyses further confirmed the spatial clustering of pharmacies in urban areas. Overall, results showed that counties and census tracts with lower populations and lower population densities tended to have fewer pharmacies. Because small populations and small population densities tend to couple with rurality, the results indicate that rural Georgia has less access to pharmacies than urban and suburban Georgia. In general, many pharmacy deserts exist in Georgia, and large urban areas have more access to pharmacies than rural areas and small cities. Rural areas of Georgia could experience the adverse effects of pharmacy deserts more than other non-rural areas. Overall, this analysis showed that there is a clear, positive relationship between rural counties and a lower number of pharmacies. Policy suggestions were proposed to increase access in pharmacy deserts. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the dentine wettability of different endodontic irrigation solutions by measuring the contact angle. Methods: Fifteen roots of recently extracted mandibular premolars were used, and cementum was eliminated. Root canals were instrumented according to the step-back technique using distilled water as an irrigant. The apical and coronal thirds of the roots were eliminated and the middle thirds were transversally sectioned. The 30 segments were embedded in acrylic resin and ground smooth and polished using 400-1200 grit papers. The dentine segments were randomly divided into six groups according to the irrigating solution they were put into contact with at 37oC for 5 mins: distilled water, 1% sodium hypochlorite, 1% citric acid, 17% EDTA, 1% citric acid + 1% sodium hypochlorite, 17% EDTA + 1% sodium hypochlorite. Then a 3 μl drop of distilled water was laid on each dentine surface with a micro-syringe and images were immediately captured with a super steady shot camera and digitalised. The contact angles were measured using ruler software. Results were analysed using one-way ANOVA and Tukey's test. Results: The contact angles were significantly reduced after pre-treatment of the dentine samples with 17% EDTA or 1% citric acid (P < 0.05), either alone or in combination with 1% sodium hypochlorite. The latter showed no significant difference compared to the control (P > 0.05). Conclusion: It was discovered that 1% citric acid and 17% EDTA, alone or in combination, increased the surface free energy of dentine. [ABSTRACT FROM AUTHOR]

The gelation of physically associating triblock copolymers in a good solvent was investigated by means of the Monte Carlo simulation and a gelation process based on the conformation transition of the copolymer that was described in detail. In our simulative system, it has been found that the gelation is closely related with chain conformations, and there exist four types of chains defined as free, dangling, loop, and bridge conformations. The copolymer chains with different conformations contribute to the formation of gel in different ways. We proposed a conformational transition model, by which we evaluated the role of these four types of chains in sol-gel transition. It was concluded that the free chains keeping the conformation transition equilibrium and the dangling conformation being the hinge of conformation transition, while the chain with loop conformation enlarges the size of the congeries and the chain with bridge conformations binds the congeries consisted of the copolymer chains. In addition, the effects of temperature and concentration on the physical gelation, the association of the copolymer congeries, and the copolymer chain conformations’ distribution were discussed. Furthermore, we employed the structure factor analysis to study the association of copolymer conformations and long-range order of the simulation system and found our results are in agreement with the previous experimental conclusions. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Of 26 patients (17 male; nine female) with a median age of 30 years (range 6-54), 18 had eyebrow AA, four had eyelash AA and nine had beard AA (Table 1). Additionally, facial hair bulbs are more superficial than their scalp counterparts and may therefore be more accessible to topical therapies.8 Only four patients (two with eyebrow AA and two with beard AA) had been on concomitant systemic treatments for moderate-to-severe scalp AA for > 6 months with failure of any facial hair regrowth. Five patients had AA affecting two facial hair-bearing sites (two with eyebrow/beard; three with eyebrow/eyelash). [Extracted from the article]

This paper presents the design and fabrication of a potentiometric sensor for the determination of carbachol in ophthalmic solutions. Carbachol is the active ingredient in certain ophthalmic solutions and its concentration must be maintained to provide its expected therapeutic result during the treatment of glaucoma. Carbachol is an analytically challenging molecule to measure because it lacks a detectable chromophore and is redox-inactive. This work demonstrates the first use of potentiometry to measure carbachol using an ion-selective electrode (ISE). Incorporating calix[4]resorcinarene as an ionophore resulted in a lower limit-of-detection (0.12 μM), larger linear response range (1 μM-10 mM), and enhanced selectivity when compared to the ionophore-free ISE. The ISE was used for direct detection of carbachol in a commercially available ophthalmic solution (without sample separation and pre-treatment steps), and the results were validated using the official US pharmacopeia benchmark method. To expand the application of this sensor, we performed real-time monitoring of carbachol's degradation, allowing for the calculation of the activation energy of its hydrolysis, an important parameter when estimating a drug's shelf-life. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A novel ant colony optimization with an automatic adjustment mechanism (AA-ACO) is proposed. • Automatic adjustment mechanism automatically can adjust the behaviour of artificial ants according to the real-time feedback information. • AA-ACO can improve the diversity of solutions and reduce the probability of falling into local optima, so that the epistasis detection power of the method is enhanced in the large-scale data set. • Detail experiment design has been given for evaluating the proposed method based on a set of simulated data sets and a real genome-wide data. Abstract Single Nucleotide polymorphisms (SNPs) are usually used as biomarkers for research and analysis of genome-wide association study (GWAS). Moreover, the epistatic interaction of SNPs is an important factor in determining the susceptibility of individuals to complex diseases. Nowadays, the detection of epistatic interactions not only attracts attention of many researchers but also brings new challenges. It is of great significance to mine epistatic interactions from large-scale data for the combinatorial explosion problem of loci. Hence, it is necessary to improve an efficient algorithm for solving the problem. In this article, a novel ant colony optimization based on automatic adjustment mechanism (AA-ACO) is proposed. The mechanism automatically adjusts the behaviour of artificial ants according to the real-time feedback information so that the algorithm can run at its best. This study also compares AA-ACO with ACO, AntEpiSeeker, AntMiner, MACOED and epiACO in a set of simulated data sets and a real genome-wide data. As shown by the experimental results, the proposed algorithm is superior to the other algorithms. [ABSTRACT FROM AUTHOR]

The article presents information on a study conducted on the subgingival penetration of a solution. It is stated that bacterial plaque is the main etiologic factor in gingivitis and periodontis, and all treatments are aimed at controlling subgingival plaque accumulation. However, it is stated that there is no evidence of complete subgingival penetration of a solution. By applying disclosing solutions to teeth before their extraction, it was found that mouthrinse applications did not penetrate subgingivally. This study was conducted to determine the relationship between sulcus depth and the degree of subgingival penetration of a solution. In the study, fluorescein solution was applied at the orifice of the gingiva in fourteen patients with gingivitis or periodontitis.

The article describes the application techniques to improve the Caries Detector, developed over the past ten years. The Caries Detector is a dental solution that helps examine infected dentin. Earlier it included basic fuchsin solution in propylene glycol, but now it has a substitute dye in place of fuchsin. The usage of this Detector allows greater accuracy in removing infected tissues. The Caries Detector is also used as a guide in removing carious enamel. It is used to disclose carious root surfaces and dental plaque. In cases of acute caries, the detector is used throughout the procedure as it stains carious enamel as well as the outer carious dentin.

The article discusses a comparative study of chlorhexidine and bisdequalinium acetate tested to groups of students who were ask to rinse their mouths with various test solutions. The findings show that only the application of bisdequalinium acetate in lozenge form provides the best result in preventing plaque formation completely, however, using the chlorhexidine solution the bisdequalinium acetate solution form obtained the poorest result. Moreover, it suggests that the way to provide the population with antiplaque agents is to provide a more convenient method which is easily used and presents no limitations of time and location.

This paper takes a longitudinal view of literature to explain the current period as disruptive technology drives an evolutionary adaptation of the construction industry in a historical socio-technological process. The authors argue the way Internet of Things (IoT) solutions are conceived as singularly focused “point solutions” undermine future opportunities. An evolutionary view is overlooked because extant literature describes technology in a particular epoch. An ecosystem perspective needs to influence IT strategy as an emerging “digital layer” transcends a smart city and continues to function long after a traditional construction project completes. We describe innovation as a succession of transformational waves in an evolutionary process that is currently manifesting as “Industry 4.0” and changing expectations for the construction industry. The paper concludes by listing emerging trends and warns existing UK construction companies must understand the transformational process they are in and learn how to adapt with a stronger drive for R&D. [ABSTRACT FROM AUTHOR]

Sticking and picking during tablet manufacture has received increasing interest recently, as it causes tablet defects, downtime in manufacturing, and yield losses. The capricious nature of the problem means that it can appear at any stage of the development cycle, even when it has been deemed as low risk by models, tests, and previous experience. In many cases, the problem manifests when transferring the process from one manufacturing site to another. Site transfers are more common now than in previous times because of the multinational nature of drug product manufacturing and the need for redundancy in manufacturing networks. Sticking is a multifactorial problem, so one single “fix” is unlikely to solve it completely, and “solutions” addressing one problem may exacerbate another. A broad-based strategy involving the API, formulation, tablet tooling, and the manufacturing process is the most likely approach to provide a robust and lasting solution. When faced with a sticking problem for the first or subsequent time, the formulator should address, in a structured way, a range of possible causes and remedies. In this article, we focus on current research and practice; on some of the common causes of sticking; mitigation and resolution strategies and solutions; and possible future directions in research. [ABSTRACT FROM AUTHOR]

[Objectives] To optimize the pet dog dyeing process of plant hair dye. [ Methods] Three factors affecting dyeing were selected including pH, concentration of dye and dyeing time. The L9(3³) orthogonal design was used to evaluate the hair colorng effect and the absorbance of cleaning solution after hair was dyed. [Results] The optimum pet dog dyeing process of plant hair dye was dye concentration of 50 mg/mL, dye pH of 7.5 and dyeing time of 1 h. [Conclusions] The coloring and fixing effects of the dye and dyeing process are good, which can lay a foundation for the development and utilization of plant dyes. [ABSTRACT FROM AUTHOR]

Abstract: Rifampicin, a semisynthetic broad‐spectrum antibiotic with antibacterial activity for a variety of pathogenic microorganisms, has three crystal forms, namely, I, II, and SV. Forms I and II are bioavailable. Solid‐state polymorphic transformation (SST) from Form II to I and solution‐mediated polymorphic transformation (SMT) from Form I to II were investigated by offline X‐ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR), respectively. Solubility and supersolubility of rifampicin Forms I and II in different solvents were obtained using the static method and turbidity meter method separately. The thermodynamic study of rifampicin proved that crystal Form I was more stable than Form II. These studies were necessary to optimize the crystallization process and crystal form controlling. The bulk density which influences significantly the drug loading capacity was clearly developed. [ABSTRACT FROM AUTHOR]

Objective: To perform a cost-effectiveness analysis of skin antiseptic solutions (chlorhexidine-alcohol (CHG) versus povidone iodine-alcohol solution (PVI)) for the prevention of intravascular-catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) in France based on an open-label, multicentre, randomised, controlled trial (CLEAN). Design: A 100-day time semi-markovian model was performed to be fitted to longitudinal individual patient data from CLEAN database. This model includes eight health states and probabilistic sensitivity analyses on cost and effectiveness were performed. Costs of intensive care unit stay are based on a French multicentre study and the cost-effectiveness criterion is the cost per patient with catheter-related bloodstream infection avoided. Patients: 2,349 patients (age≥18 years) were analyzed to compare the 1-time CHG group (CHG-T1, 588 patients), the 4-time CHG group (CHG-T4, 580 patients), the 1-time PVI group (PVI-T1, 587 patients), and the 4-time PVI group (PVI-T4, 594 patients). Intervention: 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) compared to 5% povidone iodine-69% ethanol (povidone iodine-alcohol). Results: The mean cost per alive, discharged or dead patient was of €23,798 (95% confidence interval: €20,584; €34,331), €21,822 (€18,635; €29,701), €24,874 (€21,011; €31,678), and €24,201 (€20,507; €29,136) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. The mean number of patients with CRBSI per 1000 patients was of 3.49 (0.42; 12.57), 6.82 (1.86; 17.38), 26.04 (14.64; 42.58), and 23.05 (12.32; 39.09) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. In comparison to the 1-time PVI solution, the 1-time CHG solution avoids 22.55 CRBSI /1,000 patients, and saves €1,076 per patient. This saving is not statistically significant at a 0.05 level because of the overlap of 95% confidence intervals for mean costs per patient in each group. Conversely, the difference in effectiveness between the CHG-T1 solution and the PVI-T1 solution is statistically significant. Conclusions: The CHG-T1 solution is more effective at the same cost than the PVI-T1 solution. CHG-T1, CHG-T4 and PVI-T4 solutions are statistically comparable for cost and effectiveness. This study is based on the data from the RCT from 11 French intensive care units registered with (). [ABSTRACT FROM AUTHOR]

Infliximab is a monoclonal antibody widely used for the treatment of inflammatory diseases. Over the past few years, many studies have assessed that monoclonal antibodies are prone to aggregation under stress conditions. The aim of this study was to investigate the stability of solutions of an infliximab biosimilar (Inflectra ® ) at different concentrations (0.4, 2 and 10 mg/mL). These solutions were separately submitted to three temperature conditions that are likely to happen during the drug dispensing system: −20 °C, 5 °C and 25 °C. To perform a complete characterization of infliximab physicochemical and structural stability, a wide range of analytical techniques was employed including: visual inspection, subvisible particles counting (HIAC), dynamic light scattering (DLS), size exclusion chromatography (SEC), cation exchange chromatography (CEX), and analysis of primary, secondary and tertiary structure. When stored at 25 °C, chemical instability was the main limiting factor (highlighted by CEX), while SEC showed only some acceptable variations. After a single freeze-thawing cycle, the amount of subvisible particles was significantly increased. Some variations were also visible in CEX and the hydrodynamic diameter was increased after thawing 10 mg/mL samples. In regard of these results, infliximab (Inflectra ® ) solutions should not be used after a single freeze-thawing cycle between reconstitution and administration to the patient. The results showed stability at 5 °C of up to 14 days for 10 mg/mL solutions and 90 days for 0.4 and 2 mg/mL solutions, whilst samples stored at 25 °C were stable only 7 days at 10 mg/mL and 30 days when diluted. [ABSTRACT FROM AUTHOR]

Background: Few clinical trials evaluating the efficacy of oral sweet solutions for procedures in the emergency department (ED) have been published.Objectives: To compare the efficacy of an oral sucrose solution vs. a placebo in reducing pain in infants undergoing venipuncture without cannulation.Methods: A randomized, double-blinded clinical trial was conducted in a pediatric ED. Infants 1 to 3 months old were randomly allocated to receive 2 mL of 88% sucrose or 2 mL of placebo, 2 min prior to venipuncture. The outcome measures were the difference in pain levels as assessed by the Face, Legs, Activity, Cry and Consolability Pain Scale (FLACC) and Neonatal Infant Pain Scale (NIPS) scores, crying time, and variations in heart rate.Results: Eighty-two participants were recruited. Data were analyzed for 38 patients from each group (excluding protocol deviations). The mean difference in FLACC scores 1 min post venipuncture compared with baseline was 2.84 ± .64 (sucrose) vs. 2.71 ± .62 (placebo) (p = 0.98). For the NIPS score, it was 2.32 ± .47 (sucrose) vs. 1.63 ± .49 (placebo) (p = 0.60). The difference in the median crying time was not statistically significant between the two groups: 63.0 ± 3 (sucrose) vs. 48.5 ± 5 s (placebo) (p = 0.17). No significant difference was found in participants' heart rates 1 min post venipuncture compared with baseline: 33 ± 6 (sucrose) vs. 24 ± 5 beats per minute (placebo) (p = 0.44).Conclusions: In infants 1 to 3 months of age undergoing simple venipuncture, administration of an oral sweet solution did not statistically decrease pain scores, and participants' heart rate variations and crying time were not significantly changed. [ABSTRACT FROM AUTHOR]

Solubility of drug plays major role in the process of formulation development. Solubility is the amount of solute that goes in to the solvent to form solution at given conditions of temperature, pressure and pH. Low aqueous solubility is the major problem associated with poorly water soluble drugs. Water is always the solvent of choice for liquid pharmaceuticals formulations. Most of the drugs are weakly acidic or weakly basic with poor aqueous solubility. About 40% of the drugs from newly developed chemical entities currently being discovered are poorly water soluble. The biopharmaceutical classification system of drugs suggests low water solubility, poor dissolution, and low bioavailability of Class II and IV drugs. This review article explain the various techniques used to enhance solubility of poorly water soluble drugs such as complexation of drugs, use of cosolvents, preparation of polymeric fast dissolving film, solid dispersion techniques, polymeric micelles, emulsion formation, polymeric micelles, microemulsions, pharmaceutical salts, nanomorph technology, pro-drugs, particle size reduction technologies. [ABSTRACT FROM AUTHOR]

A cycle of dropping and shaking a vial containing antibody solution was reported to induce aggregation. In this study, antibody solutions in glass prefillable syringes with or without silicone oil lubrication were subjected to the combined stresses of dropping and shaking, using a friability testing apparatus. Larger numbers of subvisible particles were generated, regardless of silicone oil lubrication, upon combination stress exposure than that with shaking stress alone. Nucleation of antibody molecules upon perturbation by an impact of dropping and adsorption of antibody molecules to the syringe surface followed by film formation and antibody film desorption were considered key steps in the particle formation promoted by combination stress. A larger number of silicone oil droplets was released when silicone oil-lubricated glass syringes containing phosphate buffer saline were exposed to combination stress than that observed with shaking stress alone. Polysorbate 20, a non-ionic surfactant, effectively reduced the number of protein particles, but failed to prevent silicone oil release upon combination stress exposure. This study indicates that stress-stability assays using the friability testing apparatus are effective for assessing the stability of biopharmaceuticals under the combined stresses of dropping and shaking, which have not been tested in conventional stress-stability assays. [ABSTRACT FROM AUTHOR]

Purpose:Thickening polymers have been used as excipients in nasal formulations to avoid nasal run-off (nasal drip) post-administration. However, increasing the viscosity of the formulation can have a negative impact on the quality of the aerosols generated. Therefore, the study aims to investigate the use of a novel smart nano-cellulose excipient to generate suitable droplets for nasal drug delivery that simultaneously has only marginally increased viscosity while still reducing nasal drips. Methods:Nasal sprays containing nano-cellulose at different concentrations were investigated for the additive’s potential as an excipient. The formulations were characterized for their rheological and aerosol properties. This was then compared to conventional nasal spray formulation containing the single-component hydroxyl-propyl methyl cellulose (HPMC) viscosity enhancing excipient. Results:The HPMC-containing nasal formulations behave in a Newtonian manner while the nano-cellulose formulations have a yield stress and shear-thinning properties. At higher excipient concentrations and shear rates, the nano-cellulose solutions have significantly lower viscosities compared to the HPMC solution, resulting in improved droplet formation when actuated through conventional nasal spray. Conclusions:Nano-cellulose materials could potentially be used as a suitable excipient for nasal drug delivery, producing consistent aerosol droplet size, and enhanced residence time within the nasal cavity with reduced run-offs compared to conventional polymer thickeners. [ABSTRACT FROM PUBLISHER]

Phospholipids and cholesterols are being spotlighted as raw materials for preparing liposomes, one of the key compounds for drug delivery systems (DDS), and as base compounds for converting water-soluble drugs to fat-soluble drugs. Other applications of phospholipids also are being explored. Nippon Fine Chemical, aware of the future of such lipids, has developed new processes for synthesizing and purifying phospholipids and is supplying them on an industrial scale. These products – used worldwide – are highly regarded as raw materials for preparing liposomes. In particular, Nippon Fine Chemical’s innovative research led to the development of “Presome®”, a base agent that facilitates the preparation of liposome solutions. To further this research, Nippon Fine Chemical has established an “Advanced Lipid Technology”. [ABSTRACT FROM AUTHOR]

Introduction: Mass spectrometry based metabolomics has become a promising complement and alternative to transcriptomics and proteomics in many fields including in vitro systems pharmacology. Despite several merits, metabolomics based on liquid chromatography mass spectrometry (LC-MS) is a developing area that is yet attached to several pitfalls and challenges. To reach a level of high reliability and robustness, these issues need to be tackled by implementation of refined experimental and computational protocols. Objectives: This study illustrates some key pitfalls in LC-MS based metabolomics and introduces an automated computational procedure to compensate for them. Method: Non-cancerous mammary gland derived cells were exposed to 27 chemicals from four pharmacological classes plus a set of six pesticides. Changes in the metabolome of cell lysates were assessed after 24 h using LC-MS. A data processing pipeline was established and evaluated to handle issues including contaminants, carry over effects, intensity decay and inherent methodology variability and biases. A key component in this pipeline is a latent variable method called OOS-DA (optimal orthonormal system for discriminant analysis), being theoretically more easily motivated than PLS-DA in this context, as it is rooted in pattern classification rather than regression modeling. Result: The pipeline is shown to reduce experimental variability/biases and is used to confirm that LC-MS spectra hold drug class specific information. Conclusion: LC-MS based metabolomics is a promising methodology, but comes with pitfalls and challenges. Key difficulties can be largely overcome by means of a computational procedure of the kind introduced and demonstrated here. The pipeline is freely available on . [ABSTRACT FROM AUTHOR]

This paper deals with the question of blow-up of solutions to nonlocal reaction-diffusion systems under various boundary conditions. Specifically, conditions on data are introduced to avoid the blow-up of the solution and, when the blow-up occurs, explicit lower and upper bounds of blow-up time are derived. [ABSTRACT FROM AUTHOR]

In this paper, we study the existence of infinitely many solutions for a class of fourth-order partially sublinear elliptic problem with Navier boundary value condition by using an extension of Clark's theorem. [ABSTRACT FROM AUTHOR]

In this article, we consider the following boundary value problem of nonlinear fractional differential equation with p-Laplacian operator: where $1<\alpha\leq2$ is a real number, $D^{\alpha}$ is the conformable fractional derivative, $\phi_{p}(s)=\vert s\vert ^{p-2}s$ , $p>1$ , $\phi_{p}^{-1}=\phi_{q}$ , $1/p+1/q=1$ , and $f:[0, 1]\times[0,+\infty)\to[0,+\infty)$ is continuous. One of the difficulties here is that the corresponding Green's function $G(t, s)$ is singular at $s= 0$ . By the use of an approximation method and fixed point theorems on cone, some existence and multiplicity results of positive solutions are acquired. Some examples are presented to illustrate the main results. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a disease that affects millions of people worldwide. In order to be managed, it requires the individuals to measure their blood glucose level in an uncomfortable way several times every day. Thereby, a reliable non-invasive, non-painful blood glucose monitoring system is desirable. Microwave technology has been regarded previously to develop such a sensor by dielectric means, but no clear dielectric characterization of blood glucose dielectric behavior has been hitherto shown. In this paper, a novel study of the effect on the dielectric behavior of water when glucose is added is presented, as a simplified case of blood glucose dielectric behavior. Different water glucose solutions have been dielectrically characterized using a transmission/reflection line method and the effect of the changes of the glucose level in the dielectric behavior has been discussed. Conclusions concerning the development of a non-invasive blood glucose sensor are offered and their validity is discussed. [ABSTRACT FROM AUTHOR]

This work aimed at developing a large-scale modular production line, which referred to coenzyme Q 10 loaded-NLC as well as its continuous and scalable emulsification and homogenization process. The production line exhibited good control over the emulsification and homogenization process and enabled the particle size of NLC below 210 nm at a throughput of 25 kg/h (for lipid solution at a flow rate of 0.4 kg/min). Among the several process parameters investigated, the size of the NLC was mainly influenced by the pre-emulsification temperature, homogenization pressure and homogenization. Suitable emulsification temperature (70 °C), homogenization pressure (600, 800 bar), and homogenization cycle (3, 4 cycles) resulted in relatively smaller particles. These results proved that coenzyme Q 10 , a model active, had been successfully loaded into the NLC. Meanwhile, the large-scale production line can be effectively applied for continuous and modular production of NLC. The line had modern networking features-essential in the Internet age-and a modular design that was easily modified and upgraded. In addition, the long-term stability over 6 month was monitored at 30 °C and at 40 °C to assess a potential effect of the laboratory scale and large scale on stability. All batches at room temperature and below were stable, and only a negligible increase in size was observed. [ABSTRACT FROM AUTHOR]