Formulation and development of paediatric orally disintegrating carbamazepine tablets.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine.

Impact of flow and temperature on non-dyspnoeic dogs' tolerance undergoing high-flow oxygen therapy.

OBJECTIVES: To prospectively describe the impact of gas flow rate and temperature on dog's tolerance of high-flow nasal oxygen therapy during recovery from anaesthesia, hypothesizing that higher flow rates and temperatures will decrease tolerance. MATERIALS AND METHODS: Twelve non-dyspnoeic client-owned dogs recovering from general anaesthesia were included in this study. After extubation, a nasal cannula was positioned and high-flow nasal oxygen therapy was initiated. Two flow rates (two or four time the theoretical minute ventilation: HF2 and HF4), each of them combined with two temperatures (31 and 37°C: T31 and T37), were randomly applied (four conditions per dog). For each condition, cardiovascular and respiratory parameters (heart rate, respiratory rate, systolic arterial blood pressure and pulse oximeter oxygen saturation), sedation score and tolerance score were recorded at initiation (T0 ) and after 10 minutes of accommodation (T10 ). RESULTS: Sedation scores were not significantly different between the four conditions. Cardiovascular and respiratory parameters were not significantly different between any condition at both T0 and T10 . Tolerance scores were good and not significantly different between any flow rate or temperature (HF2-T31: 4 (2-4), HF4-T31: 4 (2-4), HF2-T37: 4 (2-4), HF4-T37: 4 (1-4)). CLINICAL SIGNIFICANCE: The gas flow rates and temperatures studied have no impact on tolerance during the recovery period of non-dyspnoeic dogs, and high-flow nasal cannula is well tolerated. Further studies are required to confirm these results in dyspnoeic dogs.

Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges.

World population growth and aging are posing unprecedented challenges in sustaining the health of 9.1 billion people that will be occupying the planet by 2050. Although noncommunicable diseases such as cardiovascular and neurodegenerative diseases, cancer, and diabetes are among the top 10 global causes of death, they can be prevented by risk factor reduction, early detection, and adequate treatment. Since a healthy diet along with dietary supplementation could play an important role to reduce morbidity and cut off its associated health care costs, research in the food and nutrition area is required to find solutions to global challenges affecting health. As a result of the healthy living trend, dietary supplements category is growing fast, leading to an urgent need for dietitians, physicians, and policy makers to broaden the scientific evidence on the efficacy and safety of a wide range of active ingredients. Coenzyme Q10 (CoQ10), as the third most consumed dietary supplement, and as a potential candidate for the treatment of various noncommunicable diseases that are among the global top 10 causes of death, has gained interest over years. Scientific evidence regarding mainly CoQ10 efficacy and safety, as well as formulation challenges, is addressed in this review.

Study of tocopherol content and its potential antioxidant activity in commercial lipid emulsions for parenteral nutrition.

The objective of this study was to determine the content and evaluate the potential antioxidant effect of tocopherols in commercially available lipid emulsions, using a simple validated method adequate for further routine use. During the study, variability between manufacturers as well as between three non-consecutive batches of the same emulsion was observed. Furthermore, addition of α-tocopherol to lipid emulsions as excipient yields more stable emulsions and potentially a beneficial clinical effect. It was concluded that the variation of the tocopherol content between batches implies the importance of control and specification of tocopherol content by the manufacturers.

Therapeutic potential of nicotinamide adenine dinucleotide (NAD).

Nicotinamide adenine nucleotide (NAD) is a small ubiquitous hydrophilic cofactor that participates in several aspects of cellular metabolism. As a coenzyme it has an essential role in the regulation of energetic metabolism, but it is also a cosubstrate for enzymes that regulate fundamental biological processes such as transcriptional regulation, signaling and DNA repairing among others. The fluctuation and oxidative state of NAD levels regulate the activity of these enzymes, which is translated into marked effects on cellular function. While alterations in NAD homeostasis are a common feature of different conditions and age-associated diseases, in general, increased NAD levels have been associated with beneficial health effects. Due to its therapeutic potential, the interest in this molecule has been renewed, and the regulation of NAD metabolism has become an attractive target for drug discovery. In fact, different approaches to replenish or increase NAD levels have been tested, including enhancement of biosynthesis and inhibition of NAD breakdown. Despite further research is needed, this review provides an overview and update on NAD metabolism, including the therapeutic potential of its regulation, as well as pharmacokinetics, safety, precautions and formulation challenges of NAD supplementation.

Trends in the food and sports nutrition industry: A review.

This revision intends to provide an overview on the major and emerging trends in food and nutrition. Food scientists and dietitians should keep an eye on the trends shaping the food industry in order to understand consumer changes in preferences, expectations and dietary patterns; and to identify those areas that should be added to the research agenda. In addition, to comprehend the major drivers of change in the food industry, global consumer trends are also reviewed in this article. Global concerns are shaping consumer attitudes, and with an easier access to information and an unprecedented consumer power through social media, the food industry should quickly adapt to meet consumer needs. In order to meet these objectives, this review is organized in three different but interrelated sections: global consumer trends, food and nutrition trends, and trends in sports foods and nutrition. This last one is also included due to its influence over food trends, and its significant relevance as a category and food trend.

Prospective pilot study for evaluation of high-flow oxygen therapy in dyspnoeic dogs: the HOT-DOG study.

OBJECTIVES: To describe the use, effectiveness and tolerance of high-flow oxygen therapy in dyspnoeic dogs. MATERIALS AND METHODS: Prospectively, dogs in acute respiratory distress admitted to an intensive care unit between January and May 2018 that failed to respond to nasal oxygen therapy and medical stabilisation after 30 minutes were transitioned to high-flow oxygen therapy. High-flow oxygen therapy, delivered an inspired oxygen fraction of 100% using an air/oxygen blender, active humidifier, single warmed tube and specific nasal cannula. Respiratory rate, pulse oximetry (SpO2 ), heart rate and a tolerance score were assessed every 15 minutes from T0 (under nasal oxygen) to 1 hour (T60 ), and PaO2 and PaCO2 at T0 and T60 . Complications were recorded for each dog. RESULTS: Eleven dogs were included. At T60 , PaO2 , flow rate and SpO2 were significantly greater than at T0 (171 ± 123 versus 73 ± 24 mmHg; P=0.015; 18 ±12 L/minute versus 3.2 ± 2.0 L/minute, P<0.01; 97.7 ±2.3% versus 91.6 ±7.2%, P=0.03, respectively). There was no significant difference in PaCO2 , respiratory rate or heart rate between T0 and T60 . Tolerance was excellent, and there were no complications. CLINICAL SIGNIFICANCE: High-flow oxygen therapy improves markers of oxygenation in dyspnoeic dogs and is an effective means to deliver oxygen with comfort and minimal complications.

Topical Analgesia with Lidocaine Plus Diclofenac Decreases Pain in Benign Anorectal Surgery: Randomized, Double-blind, and Controlled Clinical Trial.

OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a topical formulation containing lidocaine plus diclofenac (CLIFE1) compared to lidocaine (CLIFE2), to decrease pain in benign anorectal surgery (BARS) to date not evaluated. More than 50% of patients undergoing BARS, especially hemorrhoidectomy, suffer from moderate and severe postoperative pain. This remains an unresolved problem that could be addressed with the new CLIFE1 topical treatment. METHODS: A multicenter, randomized double-blind, active-controlled parallel-group superiority trial, was conducted in two Spanish hospitals. Patients undergoing BARS (hemorrhoids, anal fistula and anal fissure) were randomized at the end of surgery at a 1:1 ratio to receive first dose either CLIFE1 (n = 60) or CLIFE2 (n = 60) anorectal topical treatment, and after every 12 h for the first three postoperative days and once a day from the fourth to sixth. The primary outcome was average of pain decrease after topical treatment, measured with visual analogue scale (VAS) by the patients themselves, the evening in the surgery day and four times daily for the first three postoperative days. RESULTS: The results of 120 patients included out of 150 selected undergoing BARS show a decrease in pain after CLIFE1 topical treatment (7.47 ± 13.09) greater than with CLIFE2 (4.38 ± 6.75), difference -3.21 95% CI (-5.75; -0.68), p = 0.008, decreasing significantly postoperative pain ( ≥ 9 mm, VAS) in 35% of patients undergoing benign anorectal surgery, compared to 18.33 % treated with lidocaine. CONCLUSIONS: The CLIFE1 topical treatment shows better analgesic efficacy than CLIFE2 in BARS.

Improving tablet coating robustness by selecting critical process parameters from retrospective data.

CONTEXT: Although tablet coating processes are widely used in the pharmaceutical industry, they often lack adequate robustness. Up-scaling can be challenging as minor changes in parameters can lead to varying quality results. OBJECTIVE: To select critical process parameters (CPP) using retrospective data of a commercial product and to establish a design of experiments (DoE) that would improve the robustness of the coating process. MATERIALS AND METHODS: A retrospective analysis of data from 36 commercial batches. Batches were selected based on the quality results generated during batch release, some of which revealed quality deviations concerning the appearance of the coated tablets. The product is already marketed and belongs to the portfolio of a multinational pharmaceutical company. RESULTS: The Statgraphics 5.1 software was used for data processing to determine critical process parameters in order to propose new working ranges. DISCUSSION AND CONCLUSIONS: This study confirms that it is possible to determine the critical process parameters and create design spaces based on retrospective data of commercial batches. This type of analysis is thus converted into a tool to optimize the robustness of existing processes. Our results show that a design space can be established with minimum investment in experiments, since current commercial batch data are processed statistically.

Study of imaging plate detector sensitivity to 5-18 MeV electrons.

Imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. We calibrated at the ELSA electron beam facility (CEA DIF) the five different available types of IPs (namely, MS-SR-TR-MP-ND) to electrons from 5 to 18 MeV. In the context of diagnostic development for the PETawatt Aquitaine Laser (PETAL), we investigated the use of stacks of IP in order to increase the detection efficiency and get detection response independent from the neighboring materials such as X-ray shielding and detector supports. We also measured fading functions in the time range from a few minutes up to a few days. Finally, our results are systematically compared to GEANT4 simulations in order to provide a complete study of the IP response to electrons over the energy range relevant for PETAL experiments.

Return to work after general surgery: A comparative study.

PURPOSES: There is scarce information on the time to return to work after general surgery. The aim of this study was to analyze time off work after elective cholecystectomy and to compare the results with those in patients undergoing other surgical interventions. METHODS: Observational and comparative study. Inclusion criteria were: being of working age and undergoing elective laparoscopic cholecystectomy (group 1) or unilateral inguinal hernia or haemorrhoidectomy (group 2). RESULTS: 36 patients were included: 18 patients in each group. Overall, return to work occurred at a mean of 35.7 days, with no significant differences (p=0.656) between groups (group 1: 36.6 days vs. group 2: 35.44 days). The reasons for not returning to work earlier were fear of complications (37.5%), pain control (37.5%), surgeon recommendation (12.5%), and general practitioner recommendation (12.5%). CONCLUSIONS: Time to recovery after laparoscopic cholecystectomy is prolonged. No statistically significant differences with less complex surgical procedures were detected.

Relationships between surface free energy, surface texture parameters and controlled drug release in hydrophilic matrices.

The study of controlled release and drug release devices has been dominated by considerations of the bulk or average properties of material or devices. Yet the outermost surface atoms play a central role in their performance. The objective of this article has been to characterize the surface of hydrophilic matrix tablets using the contact angle (CA) method to ascertain the surface free energy, and atomic force microscopy (AFM) and confocal microscopy (CM) for the physical characterization of the surface of the hydrophilic matrix. The surface free energy results obtained show that hydroxypropylmethylcellulose K15M hinders the spreading of water on the surface of the tablet, such that the concentration of HPMC K15M increases the reaction rate of the hydrophobic interactions between the chains of HPMC K15M which increases with respect to the rate of penetration of water into the tablet. In this study, we developed a new method to characterize the swelling of the tablets and established a relationship between the new method based on microswelling and the swelling ratio parameter. The surface texture parameters have been determined and the morphology of the tablets of the different formulations and the evolution of the surface morphology after interacting with the water, swelling and forming a gel layer were characterized. This work represents significant progress in the characterization of matrix tablets.

Quality by Design approach to understand the physicochemical phenomena involved in controlled release of captopril SR matrix tablets.

The aim of this study is to obtain swelling controlled release matrix tablets of captopril using the Quality by Design methodology (ICH Q8) and to know the transport mechanisms involved in captopril release. To obtain the area of knowledge, the design of experiments studying the effect of two components (HPMC K15M and ethylcellulose) at different levels has been applied, with the captopril dissolution profile as the product's most important critical quality attribute (CQA). Different dissolution profiles have been obtained with the design of experiments performed, which is a key factor in the development of controlled release matrix tablets. Kinetic analysis according to the equations of Higuchi and Korsmeyer-Peppas demonstrates that the release mechanism is a mechanism of erosion when the whole percentage of the polymer is ethylcellulose, and a diffusion mechanism when the whole percentage of the polymer is HPMC K15M. The physico-chemical characteristics of the gel layer determine the release rate of captopril. The thickness of the gel layer, the porosity which is formed in the matrix upon contact with water, pore size, the swelling rate, the erosion rate of the matrix, and the physico-chemical characteristics of captopril, are factors related to the kinetic equations described and that allow us to predict the release mechanism of captopril. A new relationship of the kinetic equations governing the in vitro behavior with the physical characteristics of the gel layer of the different formulations has been established. This study shows that the size of water-filled pores and the degree of crosslinking between the chains of HPMC K15M of the matrix are related to the exponent n of the Korsmeyer-Peppas equation and the type of transport of the captopril from within the matrix to the dissolution medium, that is, if the transport is only through water-filled pores, or if a combination of diffusion occurs through water-filled pores with a transport through continuous polymeric networks.

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression.

The SeDeM diagram expert system has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril direct compression SR matrix tablets. The application of the SeDeM diagram expert system enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM diagram expert system as system responses.

Characterization of alginate beads loaded with ibuprofen lysine salt and optimization of the preparation method.

The parameters influencing alginate ionotropic gelation and the production of alginate beads loaded with hydrosoluble ibuprofen lysine salt (IBU-L) were studied, as well as the optimization of the method for its attainment. A three-factor and three-level factorial design (3(3)) was carried out to determine the influence of three experimental variables: polymer concentration, CaCl2 concentration, and curing time on the dependent variables drug load and encapsulation efficiency. The effect of the pH used in the preparation bath was also evaluated. Concentrations of CaCl2 and pH of gelling bath were seen to affect bead formation and stability as well as their ability to properly entrap the drug. In this work, IBU-L was used as a model of a non-steroidal anti-inflammatory drug with good solubility in alginate solutions. IBU-L was successfully encapsulated in alginate beads obtained by the ionotropic gelation method. The obtained alginate matrixes are able to modify the release of the entrapped IBU-L and this occurs in a pH-sensitive way that can be correlated with the swelling behaviour of the alginate-produced beads. Morphological characteristics were evaluated by means of scanning electron microscopy.

[Waiting list in general and digestive surgery: patient expectations, quality of life during waiting time and overall satisfaction]. / Lista de espera en Cirugía General y Digestiva: expectativas del paciente, calidad de vida durante la espera y grado de satisfacción.

INTRODUCTION: The structural resources of the National Health system are limited, and therefore early surgery cannot be performed on all patients. The objective was to analyse the satisfaction perceived by the patient as regards the delay of treatment by waiting list of three types of surgery. The influence of expectations on waiting times, and impaired quality of life due to the clinical symptoms during the delay, were studied. MATERIAL AND METHODS: A prospective study was conducted using a postal questionnaire. We compared the expectations (scale of 1 to 5), the impact on quality of life for symptoms (scale of 1 to 5) and the level of patient satisfaction (scale of 1 to 5) with respect to time on the waitng list for cholelithiasis, inguinal hernia and haemorrhoids. The predictors of patient dissatisfaction were analysed. RESULTS: A total of 57 patients were included. When comparing the characteristics of patients with and without satisfaction over time on the waiting list, days on the waiting list (P=.044), the change in the quality of life due to the symptoms (P=.028), and expectations (P<.001) were significantly different between the two groups. In the multivariate analysis, the expectation was associated with patient dissatisfaction as regards the time on waiting list (OR: 3.14 95% CI: 5.91 to 220.73, P<.001). CONCLUSIONS: The level of patient dissatisfaction is associated with expectations about time in waiting list.

Impact of physical parameters on particle size and reaction yield when using the ionic gelation method to obtain cationic polymeric chitosan-tripolyphosphate nanoparticles.

Ionic gelation is the most frequently used method to obtain chitosan-tripolyphosphate nanoparticles due to its simplicity and because it does not generate waste solvents in the samples prepared. This paper presents a study of the physical factors involved in this method for obtaining nanoparticles in order to determine which of them significantly influences the particle size of polymeric nanoparticles made from low-molecular-weight chitosan, without any additional chemical treatment, with the aim of standardising and optimising the method conditions, in addition to establishing the reaction yield. The results indicate that stirring speed during ionic gelation reaction is decisive for the size of the nanoparticles obtained. Furthermore, it thus follows that the stirring speed during ionic gelation significantly affects reaction yield, and therefore, by manipulating this parameter a greater proportion of nanoparticles of a given size range can be obtained.

Total organic carbon (VCSN and VWP) and HPLC analysis for cleaning validation in a pharmaceutical pilot plant.

This paper presents a useful method using total organic carbon analyzers employing both combustion and wet oxidation for validating equipment cleaning procedures and verifying cleaning in a pharmaceutical pilot plant. The results are compared with those obtained using high-performance liquid chromatography. The study summarizes the initial steps that should be taken into account and focuses particularly on the solutions to some of the most critical considerations (e.g., glass material, detection and quantification limits, recovery). Also described are the calculation of control limits and the good results obtained.

In vitro evaluation of the effectiveness and cytotoxicity of meglumine antimoniate microspheres produced by spray drying against Leishmania infantum.

The aim of the present study was to evaluate the in vitro activity and cytotoxicity of meglumine antimoniate microspheres produced by spray drying on Leishmania infantum and the effect of the excipients used in them. The parasite strain shows sensitivity to the meglumine antimoniate microspheres prepared. All the antimony IC50 values from encapsulated meglumine antimoniate (3.80 +/- 0.34 to 9.53 +/- 0.70 microg SbV/ml for promastigotes assay) are considerably lower compared to the mean value of IC50 in Glucantime solution (112 +/- 12.74 microg SbV/ml). Interesting IC50 values for the excipient chitosan (112.64 +/- 0.53 mg/ml for promastigotes and 100.81 +/- 26.45 mg/ml for amastigotes) were obtained (without cytotoxic activity), whereas the rest of the excipients did not show any activity. This new delivery system could offer a new pharmacological tool for the treatment of leishmaniosis that reduces the doses required, lowering toxic side effects because of meglumine antimoniate.