Background:Colour plays an important role in shaping consumer experiences, and in the context of medicines, it may influence patients' expectations, behaviours, and treatment adherence. There is limited research on how children respond to medicine colour, despite their increased sensitivity to sensory cues. A previous literature review indicated that colour may affect medicine acceptability in children but highlighted the need for further research. This cross-sectional study aimed to fill that gap by directly collecting children's opinions on the colour of oral medicines through an online survey, targeting a diverse paediatric population across age, health status, and countries in Europe. Methods:The survey, developed by UCL School of Pharmacy UCL REC (ID 26765/001) and reviewed by experts of the European Young Persons Advisory Group Network (eYPAGnet), was translated into five languages and distributed via QR codes and anonymous links. Response collection occurred between September 2024 and April 2025. Participants included children aged 3 to 18, with parental assistance when needed and parental consent. Responses were analysed using the software R Studio. Results:Out of 669 people who accessed the survey, 382 completed it. For liquids, pink (23%), colourless (16.5%), and blue (15.2%) were most preferred. Reasons included appealing look and taste associations (e.g., strawberry for pink). For solids, white (29.1%), pink (18%), and blue (12.5%) led, with neutral appearance and berry-related flavours cited. Statistically significant gender and age differences in preferences emerged, while variations by health, or country were not always significant. Ratings for previously used medicines highlighted preference for purple, pink, and blue, while white and colourless received moderate scores. A statistically significant link between taste and colour emerged (ρ = 0.42, p-value 2.2 × 10-16), suggesting that the colour of a medicine may influence children's anticipation of its taste and shape their overall expectations of the treatment experience. Conclusion:This study offers valuable insight into children's preferences for medicine colour. Pink and blue were associated with sweet/flavourful tastes, while neutral colours were perceived as tasteless, particularly by participants aged 12-18 years. These findings can inform paediatric formulation strategies, particularly the selection and use of colouring agents, in alignment with current regulatory requirements when their inclusion is considered necessary.
The aim of this study was to develop an age-appropriate tablet of mebendazole 500 mg to be used in large donation programs by the World Health Organization (WHO) for preventive chemotherapy of soil-transmitted helminth (STH) infections in pre-school and school-age children living in tropical and subtropical endemic areas. To that end, a new oral tablet formulation was developed that can be either chewed or given to young (& GE;1 year old) children by spoon after rapid disintegration to a soft mass with the addition of a small amount of water directly on the spoon. Although the tablet was manufactured using conventional fluid bed granulation, screening, blending, and compression processes, one of the main challenges was to combine properties of a chewable, dispersible, and regular (solid) immediate release tablet to meet the predefined requirements. The tablet disintegration time was below 120 s, allowing for administration by the "spoon method". The tablet hardness was higher (160-220 N) than normally applicable for chewable tablets, permitting shipment along a lengthy supply chain in a primary 200-tablet count bottle packaging. In addition, the resulting tablets are stable for 48 months in all climatic zones (I-IV). In this article, several aspects of the development of this unique tablet are described, including formulation, process development, stability, clinical acceptability testing, and regulatory filing.
The colour of a product plays an important role in consumer experiences, and in the context of pharmaceutical products, this could potentially affect a patient's expectations, behaviours, and adherence. Several studies have been conducted on adults, but little is known about children's opinions on colours of medicines and to what extent medicines' colour affects their acceptability. To address this gap, a systematic search in PubMed, Scopus, MEDLINE, and Web of Science was conducted. Two authors independently screened the titles, abstracts, and references of all articles and selected studies conducted on children (0-18 years old), assessing children's preferences or opinions about colour of oral dosage forms as either a primary or secondary objective or as an anecdotal record. A total of 989 publications were identified and, after screening, 18 publications were included in the review. Red and pink were the most liked colours and there appeared to be a relationship between the colour of a medicine and expected taste/flavour. The review also highlighted a scarcity of information, usually collected as an anecdotal record. Several gaps in the current knowledge were underlined, emphasizing the need of patient-centred studies to understand if the use of certain colours can improve or worsen the acceptability of a paediatric medicine. This will help inform pharmaceutical manufacturers and regulators on the role and need of colours in children's medicines beyond quality purposes.
Improved global access to novel age‐appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age‐appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children‐centric formulation design for new chemical entities, or to repurpose/reformulate off‐patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age‐appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however, the proposed paediatric Quality Target Product Profile could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product.
A workshop on "Pediatric Formulation Development: Challenges of Today and Strategies for Tomorrow" was organized jointly by the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI), the U.S. Food and Drug Administration (FDA) and the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Drug Product Pediatric Working Group (PWG). This multidisciplinary, pediatric focused workshop was held over a two-day period (18-19 Jun 2019) and consisted of participants from industry, regulatory agencies, academia and other organizations from both US and Europe. The workshop consisted of sequential sessions on formulation, analytical, clinical, and regulatory and industry lessons learned and future landscape. Each session began with a series of short framing presentations, followed by facilitated breakout sessions and panel discussion. The formulation session was dedicated to three main topics pertaining to drug product acceptability, excipients in pediatrics and oral administration device considerations. The analytical session discussed key considerations for dosing vehicle selection and analytical strategies for testing of different dosage forms, specifically mini-tablets (multiparticulates). The clinical session highlighted the influence of pediatric pharmacokinetics prediction on formulation design, pediatric drug development strategies and clinical considerations to support pediatric formulation design. The regulatory and industry lessons learned and future landscape session explored the regional differences that exist in regulatory expectations, requirements for pediatric formulation development, and key patient-centric factors to consider when developing novel pediatric formulations. This session also discussed potential collaboration opportunities and tools for pediatric formulation development. This manuscript summarizes the key discussions and outcomes of all the sessions in the workshop with a broadened review and discussion of the topics that were covered.
PURPOSE:The compatibility of doripenem diluted for infusion with 82 other drugs during simulated Y-site administration was studied.METHODS:Five-milliliter samples of doripenem 5 mg/mL in 5% dextrose injection and separately in 0.9% sodium chloride injection were combined with 5 mL of 82 other drugs, undiluted or diluted in 5% dextrose injection or 0.9% sodium chloride injection. Visual examinations were performed with the unaided eye in fluorescent light and using a Tyndall beam to enhance visualization of small particles and low-level turbidity. The turbidity of each sample was measured, and particulate content was evaluated. Samples were inspected initially and one and four hours after preparation.RESULTS:Of the drugs tested, doripenem 5 mg/mL in 5% dextrose injection and in 0.9% sodium chloride injection was incompatible with diazepam, potassium phosphates, and undiluted propofol. Doripenem 5 mg/mL in 0.9% sodium chloride injection but not in 5% dextrose injection was incompatible with amphotericin B-containing drugs due to the diluent. Doripenem was found to be compatible when combined with the other 75 drugs for at least four hours.CONCLUSION:Doripenem 5 mg/mL in 5% dextrose injection or in 0.9% sodium chloride injection was physically compatible for four hours at room temperature with 75 drugs during simulated Y-site administration. Three drugs combined with doripenem in 5% dextrose injection or 0.9% sodium chloride injection and 7 drugs combined with doripenem in 0.9% sodium chloride injection resulted in unacceptable precipitation or an increase in measured haze and should not be simultaneously administered with doripenem admixtures.
Abstract A reversed-phase high performance liquid chromatographic (RP-8; acetonitrile-water gradient) separation procedure was developed for detecting bryostatins 1–12, using a photodiode array detector system. While bryostatins 6 and 9 were found to co-elute they were easily separated using a silica gel column with 9:1 n-hexane-n-propanol as eluent.
A capillary electrophoresis (CE) method has been developed as an alternative method for the determination of the inorganic degradation products sulfate and sulfamate in topiramate drug product and drug substance, currently performed by ion chromatography. The anions are separated in a background electrolyte containing potassium chromate and boric acid, followed by indirect UV detection. By adding tetradecyltrimethylammonium bromide to the electrolyte, analysis is performed under co-electroosmotic flow conditions. Variations in injection volumes and migration times are compensated for by use of an internal standard. The validation of the method, which was performed according to ICH guidelines (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) [1], comprises specificity, accuracy, linearity, precision, sensitivity and robustness. In addition, the results of an actual tablet sample analysis obtained by this CE method are statistically shown to be in close agreement with those obtained by an ion chromatographic method.
In today's world, we face a significant degree of miniaturization in many aspects of technology. Wonders of miniaturization are also occurring in the areas of physical and biological sciences. The development of a 21st-century technology has enabled investigations and processes to be performed at concentration levels that were previously unimaginable. Unfortunately, as the concentration levels and quantities of samples involved become progressively smaller, chemical-scale analytical technology rapidly approaches its limit of usefulness.
The use capillary electrophoresis (CE) for clinically relevant assays in attractive since it often presents many advantages over contemporary methods. The small-diameter tubing that holds the separation medium has led to the development of multicapillary instruments, and simultaneous sample analysis. Furthermore, CE is compatible with a wide range of detectors, including UV-Vis, fluorescence, laser-induced fluorescence, electrochemistry, mass spectrometry, radiometric, and more recently nuclear magnetic resonance, and laser-induced circular dichroism systems. Selection of an appropriate detector can yield highly specific analyte detection with good mass sensitivity. Another attractive feature of CE is the low consumption of sample and reagents. However, it is paradoxical that this advantage also leads to severe limitation, namely poor concentration sensitivity. Often high analyte concentrations are required in order to have injection of sufficient material for detection. In this regard, a series of devices that are broadly termed ‘analyte concentrators’ have been developed for analyte preconcentration on-line with the CE capillary. These devices have been used primarily for non-specific analyte preconcentration using packing material of the C18 type. Alternatively, the use of very specific antibody-containing cartridges and enzyme-immobilized microreactors have been demonstrated. In the current report, we review the likely impact of the technology of capillary electrophoresis and the role of the CE analyte concentrator-microreactor on the analysis of biomolecules, present on complex matrices, in a clinical laboratory. Specific examples of the direct analysis of physiologically-derived fluids and microdialysates and presented, and a personal view of the future of CE in the clinical environment is given.
Electrochromatography is a chromatographic method in which the mobile phase (liquid or supercritical fluid) is “pumped” through a stationary phase in a microbore or capillary column by electroosmosis using an electric field. The technique permits separation of charged and uncharged compounds with higher resolution and superior efficiency when compared with micro-HPLC with an identical column. It is desirable to work with packed capillary columns with wide diameter in electrochromatography in order to improve detectability and column loadability. This study shows that we have moved a step forward towards this goal in spite of problems and difficulties, due to Joule heating, frit making and column packing in using wide-diameter columns. The paper demonstrates that the pressure pump of micro-HPLC with a commercially available 320 μm I.D. column can be replaced by the electroosmotic “pump” of capillary zone electrophoresis. Experiments were carried out in a chromatographic system under both electroosmosis and pressure-driven flow with 320 and 50 μm I.D. columns packed with 3- and 5-μm ODS. The advantage of electrochromatography over conventional micro-HPLC is shown.
During a large‐scale isolation of bryostatin 1, NMR measurements indicated that parts of the published 13 C and 1 H NMR assignments had to be revised. These reassignments were based on extensive homonuclear and heteronuclear one‐ and two‐dimensional NMR techniques performed at 500 MHz. These independently obtained assignments are also in good agreement with the revised assignments and structure of bryostatin 3.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRevised structure of bryostatin 3 and isolation of the bryostatin 3 26-ketone from Bugula neritina [Erratum to document cited in CA115(3):26268m]Daniel E. Schaufelberger, Gwendolyn N. Chmurny, John A. Beutler, Mary P. Koleck, A. Belinda Alvarado, Brigitte W. Schaufelberger, and Gary M. MuschikCite this: J. Org. Chem. 1991, 56, 19, 5736Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://pubs.acs.org/doi/10.1021/jo00019a058https://doi.org/10.1021/jo00019a058research-articleACS PublicationsRequest reuse permissionsArticle Views36Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Bryostatin 3 and the corresponding 26-ketone 5, which represents a new bryostatin, were isolated from the marine bryozoan Bugula neritina (Bugulidae). Spectroscopic data from 2D NMR studies indicate that the structure of bryostatin 3 (3) has to be revised to structure 4. Bryostatin 3 showed [H-3]phorbol dibutyrate receptor displacement activity similar to that of bryostatin 1, whereas the corresponding 26-ketone 5 was significantly less active.
Lyngbya majuscula and Croton cuneatus were used as prototypes for the dereplication of phorbol ester receptor binding activity using a combination of hplc-uv and online phorbol dibutyrate (PDBu) receptor binding and batch fractionation over either Si gel or diolbonded Si gel. Debromoaplysiatoxin was responsible for the bioactivity of Lyngbya, whereas a complex of potent phorbol esters was detected in C. cuneatus.
A novel process was designed for the large-scale isolation of bryostatin 1 from the bryozoan Bugula neritina L. in order to obtain multigram quantities of highly pure material for formulation studies, preclinical toxicology, and clinical trials in cancer patients. Multigram quantities of bryostatin 1 were obtained from a collection of approximately 10,000 gallons of wet animal. A phorbol dibutyrate (PDBu) receptor binding assay and hplc with photodiode array detection were used for the design, validation, and control of the isolation process.
AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.