Recently trans-resveratrol (trans-RSV) has received great attention due to its prophylactic and therapeutic properties. Its limited bioavailability provides compelling evidence of the need for more suitable formulations in order to attain better clinical effectiveness. Some physicochemical properties of trans-RSV are still unknown or research findings are contradictory. Therefore, this paper presents newly determined trans-RSV solubility and stability at various pH and temperatures, and the importance of such data for the studies of novel trans-RSV-loaded nanofibers. In acidic pH trans-RSV was stable, whereas its degradation started to increase exponentially above pH 6.8. Consequently, it is worthwhile to note that special consideration has to be dedicated to long dissolution testing or biological assays on cell lines in order to obtain relevant data. Measurements were done by validated UV/VIS spectroscopy, HPLC, and newly developed UPLC methods. Specificity was confirmed for HPLC and UPLC method, where as UV/VIS spectroscopy resulted in false higher trans-RSV concentrations in conditions under which it was not stable (alkaline pH, light, increased temperature). The study is of interest because it draws attention to the importance of careful selected experimental conditions, their influence on the trans-RSV stability and the implications this has for formulation development, storage, and maintenance of therapeutic doses.
COBISS.SI-ID: 3848561
The purpose of this study was to compare different solidification techniques (i.e. adsorption technique,spray-drying process, high-shear granulation, fluid-bed granulation) for preparing solid SMEDDS powders by using solid carriers identified as appropriate and to produce a single (tablets) or multi unit (minitablets) solid dosage form based on prepared solid SMEDDS loaded with naproxen in a dissolved (6% w/w) or supersaturated (18% w/w) state. Among the solidification techniques and carriers tested, the powders produced using the spray-drying process and maltodextrin (MD) as a carrier exhibited the best self-microemulsifying properties, comparable with liquid SMEDDS. Furthermore, DoE (Design of Experiments) showed that pressure at the nozzle and pump speed (regulating feed flow rate) applied during spray drying had a major and significant influence on self-microemulsifying properties (mean droplet size and PDI) of the solid SMEDDS prepared. Furthermore, it was shown that compression of solid SMEDDS into (mini) tablets influences its self-microemulsifying properties in a negative direction. This resulted in lowering the dissolution profile of naproxen from tablets and minitablets in comparison with liquid and solid SMEDDS. However, all compressed SMEDDS formulations still had considerable influence on the dissolution profile and solubility enhancement of naproxen.
COBISS.SI-ID: 3915121
The aim of the present study is to evaluate the influence of factors such as biopharmaceutical properties and study protocol on the emptying of pellets from the human stomach in a fed state. A systematic literature search for data on human gastric emptying of pellets from a fed stomach state investigated by g-scintigraphy was carried out. After selection of comparable data, a joint statistical analysis on the basis of multiple linear regression with 132 individual t50 values (time for 50% of the pellets to be emptied from the stomach) was performed. Parameters such as a second meal administration that can influence t50 values were also examined and included into the interpretation of the results. The results showed that an increase in the caloric value of the meal in the interval between 1200 and 3600 kJ increased the mean t50 value. Pellets with a density of 2.8 g/cm3 remained in the stomach longer than pellets of usual density with the same caloric value of the meal. Pellets incorporated in a tablet are emptied faster from the stomach than encapsulated pellets. A 45-min delay in the application of pellets after the start of the meal significantly diminished the mean t50 value, compared with application immediately after consuming the meal. Thus, in the development of non-disintegrating pellets intended for fed-state application, all of these cited factors should be considered because of their potential influence on the gastric residence time.
COBISS.SI-ID: 3846769
There is a lack of comparative effectiveness research among Attention deficit hyperactivity disorder (ADHD) drugs in terms of efficacy and acceptability, where bupropion is compared with atomoxetine, lisdexamfetamine and methylphenidate. The main aim of this work was to compare the efficacy and acceptability of these drugs in children and adolescents using a metaanalysis. A literature search was conducted to identify double-blind, placebo-controlled, noncrossover studies of ADHD. PubMed/Medline and Clinicaltrials.gov were searched. Comparative drug efficacy to placebo was calculated based on the standardized mean difference (SMD), while the comparative drug acceptability (all cause discontinuation) to placebo was estimated on the odds ratio (OR). In total 28 trials were included in the meta-analysis. Efficacy in reducing ADHD symptoms compared to placebo was small for bupropion (SMD = -0.32, 95% CI; -0.69, 0.05), while modest efficacy was shown for atomoxetine (SMD = -0.68, 95% CI; -0.76, -0.59) and methylphenidate (SMD = -0.75, 95% CI; -0.98, -0.52) and highefficacy was observed for lisdexamfetamine (SMD = -1.28, 95%CI; -1.84, -0.71). Compared to placebo treatment discontinuation was statistically significantly lower for methylphenidate (OR=0.35, 95% CI; 0.24, 0.52), while it was not significantly different for atomoxetine (OR = 0.91, 95% CI; 0.66, 1.24), lisdexamfetamine (OR = 0.60, 95% CI, 0.22, 1.65), and bupropion (OR = 1.64, 95% CI; 0.5, 5.43). Limitations The heterogeneity was high, except in a tomoxetine trials. The crossover studies were excluded. The effect sizes at specific time points were not computed. Studies with comorbid conditions, except those reporting on oppositional defiant disorder, were also excluded. All studies involving MPH were combined. The results suggest that lisdexamfetamine has the best benefit risk balance and has promising potential for treating children and adolescents with ADHD. More research is needed for a better clinical evaluation of bupropion.
COBISS.SI-ID: 3827569
Purpose: Several electronic databases which report the prevalence of drug-druginteractions (DDIs) are used as a tool for evaluation of potentially harmful DDIs. The aim of our review was to evaluate the usability and appropriateness of commercially available electronic databases which assess the prevalence of potential DDIs. Methods: The systematic electronic literature search was conducted with the following search terms: "database" AND "software," and "drug-drug interactions" AND "database," and the inclusion and exclusion criteria were applied in order to identify the publications of interest. Results: A total of 3766 papers were identified by systematic search. After applying inclusion and exclusion criteria, 38 publications were included in the analysis. The most commonly used software in the included studies was Micromedex Drug-Reax, for which some authors argue to be the most reliable due to highest sensitivity. It gives information about clinical consequences of DDIs, classifies underlying mechanism and onsetof the adverse outcome (either rapid, or delayed) as well as severity (such as minor, moderate, or major), and provides the level of evidence which supports this information. This data is also provided by Drug Interaction Facts", Lexi-Interact", and Pharmavista". A small number of studies which compared assessment of DDIs with electronic database and the clinicianʼs assessment showed large discrepancy in number and relevance of detected DDIs. The overlap was in some cases as low as 11 %.
COBISS.SI-ID: 3795313