114 research outputs found
Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results
Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor
SeDeM as a Tool to Validate Drug Substance Manufacturing Processes and Assess Scalability and Suitability for Direct Compression: Supplier Screening
During the development of an oral solid form of a drug substance, a thorough understanding of the critical material attributes is necessary, as the physical properties of the active pharmaceutical ingredient (API) can profoundly influence the drug product's manufacturability, critical quality attributes, and bioavailability. The objective of this study was to validate the manufacturing process of the drug Linezolid from three different sources at both the pilot and industrial scale and to identify differences in critical material attributes between the API manufacturers. Furthermore, the scalability factor between the pilot and industrial scale and the suitability of a process for direct compression were also evaluated. In the present study, the different sources of API were characterized by SeDeM methodology, particle size distribution, and scanning electron microscopy determinations. The statistical analysis revealed that no statistically significant differences were found for any of the parameters under study for the same API source analyzed on both scales. On the other hand, for most of the parameters evaluated, statistical differences were observed between the different sources. It was concluded that SeDeM was able to successfully validate the API manufacturing process, assess scalability, and distinguish between sources. Therefore, it could be highly valuable in the formulation phase to select the best API source. Keywords: Linezolid; SeDeM expert system; critical material attribute; critical quality attribute; direct compression; drug substance manufacturers; particle size; powder characterization; preformulation; process validation
Methods for Developing a Process Design Space Using Retrospective Data
Prospectively planned designs of experiments (DoEs) offer a valuable approach to preventing collinearity issues that can result in statistical confusion, leading to misinterpretation and reducing the predictability of statistical models. However, it is also possible to develop models using historical data, provided that certain guidelines are followed to enhance and ensure proper statistical modeling. This article presents a methodology for constructing a design space using process data, while avoiding the common pitfalls associated with retrospective data analysis. For this study, data from a real wet granulation process were collected to pragmatically illustrate all the concepts and methods developed in this article
Comparative Analysis of the Physicochemical and Biological Characteristics of Freeze-Dried PEGylated Cationic Solid Lipid Nanoparticles
Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs). Several parameters were analyzed, including the particle size, polydispersity index, zeta potential, shape, stability, cytotoxicity, and loading efficiency. Five different formulations with specific PEGs were developed and compared in both suspended and freeze-dried states. Small, homogeneous, and cationic suspended nanoparticles were obtained, with the Gelucire 50/13 (PEG-32 hydrogenated palm glycerides; Gelucire) and DSPE-mPEG2000 (1,2-distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjungate-2000; DSPE) formulations exhibiting the smallest particle size (similar to 170 nm). Monodisperse populations of freeze-dried nanoparticles were also achieved, with particle sizes ranging from 200 to 300 nm and Z potential values of 30-35 mV. Notably, Gelucire again produced the smallest particle size (211.1 +/- 22.4), while the DSPE and Myrj S100 (polyoxyethylene (100) stearate; PEG-100 Stearate) formulations had similar particle sizes to CO-cSLNs (similar to 235 nm). The obtained PEGylated nanoparticles showed suitable properties: they were nontoxic, had acceptable morphology, were capable of forming SLNplexes, and were stable in both suspended and lyophilized states. These PEG-cSLNs are a potential resource for in vivo assays and have the advantage of employing cost-effective PEGs. Optimizing the lyophilization process and standardizing parameters are also recommended to maintain nanoparticle integrity
Robustness Optimization of an Existing Tablet Coating Process Applying Retrospective Knowledge (rQbD) and Validation
The objective of these studies is to verify and validate the improvement in the inter-tablet coating uniformity for an industrially commercialized coated tablet, without involving changes in the approved registration dossier. Using the CPP (critical process parameters) determined from previous retrospective statistical analysis, the recommended working ranges are identified. Retrospective analysis showed that the design of experiments (DoE) provided an improved process variable configuration. Therefore, it is decided to study two critical parameters: Product temperature and drum speed, with an additional 22 experimental design. The quality results of the samples analyzed show that the aesthetic defects of the batches made with the new working ranges have been reduced. These results have also been corroborated with the 42 industrial batches manufactured with the new ranges. With the optimized parameters, tablets have been coated and the suitability of the model determined. The results demonstrated the overall reliability and effectiveness of the proposed Quality by Design approach and provides a useful tool to help optimize the industrial coating process. This study confirms that it is possible to optimize and validate the manufacturing process of an existing commercial product by means of a DoE with retrospective data. Therefore, no variation in the dossier is required
Dialysis is a key factor modulating interactions between critical process parameters during the microfluidic preparation of lipid nanoparticles
Manufacturing lipid nanoparticles through microfluidic mixing can be approached from a Quality by Design perspective. Research involving critical process parameters seems to focus on the total flow and flow rate ratio, thus other process variables, such as dialysis, are underestimated. This study used a Design of Experiments to identify the influence of critical process parameters on particle size, polydispersity index, and zeta potential. A response surface Design of Experiments modeled the influence of: total flow (400 to 4000 ÎĽL min-1); flow rate ratio (3 to 9) and dialysis (yes/no). Results suggest that dialysis is a crucial parameter that strongly influences particle size and zeta potential and moderately affects polydispersity index. The flow rate ratio's relevance decreases when dialysis is performed. As the purification method can change the influence of other process parameters, it should be an integrated part of the microfluidic manufacturing of lipid nanoparticles instead of an extra step.This work was supported by the University of Costa Rica [OAICE-64-2019]; Spanish Ministry of Science and Innovation grant PID2020-118859GB-100; and the Andalusian Government grants P20_01269 and P20_01271
Food and Sports Nutrition Trends
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
Palatability and stability studies to optimize a carvedilol oral liquid formulation for pediatric use
Carvedilol (CARV) is a blocker of α- and β- adrenergic receptors, used as an “off-label” treatment for cardiovascular diseases in pediatrics. Currently, there is no marketed pediatric-appropriate CARV liquid formulation, so its development is necessary. Palatability (appreciation of smell, taste, and aftertaste) is a key aspect to be considered during the development of pediatric formulations since only formulations with good palatability also have adequate acceptability in this population. Consequently, the aim of this research was to assess the palatability and acceptability of different CARV formulations using an in vivo taste assessment (ID Number PR103/22) in order to select the highest palatability-rated CARV formulation. The preparation of CARV formulations was based on a reference 1 mg/mL CARV solution, which contains malic acid as a solubilizing agent. Subsequently, sucralose and flavoring agents were added and mixed until complete dissolution to the corresponding formulations. Adult volunteers participated in this study and evaluated the taste and odor of various CARV formulations through a questionnaire and a sensory test. The mean palatability score, measured on a 10-point scale, increased from 1.60 for the unflavored control to 7.65 for the highest-rated flavored formulation. Moreover, the bitterness of the optimized CARV formulation was reduced from 66.67% to 17.86%, and the taste pleasantness was increased from 25/100 to 73/100. This optimized CARV formulation contains a sweetening agent, sucralose, in addition to two flavoring agents at appropriate concentrations for pediatrics. Furthermore, the physicochemical and microbiological stability of the optimized CARV formulation were evaluated for 6 months at 25, 30, and 40 °C, in addition to in-use stability for 15 days at 25 °C, whose results were confirmed. Thus, we successfully developed a palatable CARV liquid solution that contains excipients appropriate for pediatrics and is stable under the studied conditions.</span
Excipients in the Paediatric Population: A Review
This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory agencies. On the one hand, this review describes the most frequent excipients used in paediatric medicine formulations, identifying the compounds that scientific literature has marked as potentially harmful regarding the side effects generated after exposure. On the other hand, this review also highlights the importance of carrying out safety -checks on the excipients, which, in most cases, are linked to toxicity studies. An excipient in the compilation of paediatric population databases is expected to target safety and toxicity, as in the STEP database. Finally, a promising pharmaceutical form for child population, ODT (Orally Disintegrating Tablets), will be studied
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