Colour of Medicines and Children's Acceptability? A Systematic Literature Review of Children's Perceptions about Colours of Oral Dosage Forms.

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.

Complete genome sequence of zoysia mosaic virus, a novel member of the genus Poacevirus.

Here, we report the detection and characterization of the genome of a novel poacevirus isolated from Zoysia matrella (Merrill) imported into the United States from Japan. The novel virus, tentatively named "zoysia mosaic virus" (ZoMV), is a single-stranded RNA virus with a genome of 9,728 nucleotides (nt) in length, encoding a large putative polyprotein of 3,119 amino acids (aa). The ZoMV genome is closely related to the triticum mosaic virus (TriMV; FJ263671) genome, with 57.18% nt and 51.74% aa sequence identity in the polyprotein region. Moreover, phylogenetic analysis showed that ZoMV is closely related to all other members of the genus Poacevirus. A survey of imported grasses showed that ZoMV was detected only in zoysiagrass. This is the first report of the complete genome sequence of a novel viral pathogen of zoysiagrass of the genus Poacevirus, for which we propose the binomial species name "Poacevirus zoisiae".

Path towards efficient paediatric formulation development based on partnering with clinical pharmacologists and clinicians, a conect4children expert group white paper.

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.

Genomic characterization of silvergrass cryptic virus 1, a novel partitivirus infecting Miscanthus sinensis.

In the present study we report the identification of a novel partitivirus recovered from Miscanthus sinensis, for which the provisional name "silvergrass cryptic virus 1" (SgCV-1) is proposed. High-throughput sequencing (HTS) and rapid amplification of cDNA ends (RACE) allowed the assembly of the complete sequence of each double-stranded RNA genome segment of this novel virus. The largest dsRNA segment, dsRNA1 (1699 bp), was predicted to encode a viral RNA-dependent RNA polymerase protein (RdRp) with 478 aa, and dsRNA2 (1490 bp) and dsRNA3 (1508 bp) were predicted to encode putative capsid proteins (CPs) with 347 and 348 aa, respectively. SgCV-1 has the highest amino acid sequence identity (≤ 70.80% in RdPp and ≤ 34.5% in CPs) to members of the genus Deltapartitivirus, family Partitiviridae, especially to unclassified viruses related to members of this genus. Its genome segment and protein lengths are also within the range of those of deltapartitiviruses. Moreover, phylogenetic analysis based on RdRp amino acid sequences also showed clustering of this novel virus with the related unclassified deltapartitiviruses. An RT-PCR survey of 94 imported M. sinensis samples held in quarantine identified seven additional samples carrying SgCV-1. This new virus fulfils all ICTV criteria to be considered a new member of the genus Deltapartitivirus.

Rats can predict aversiveness of Active Pharmaceutical Ingredients.

Taste is crucial for patient acceptability and compliance with prescribed medicines, in particular with pediatric patients. Evaluating the taste of new active pharmaceutical ingredients (APIs) is therefore essential to put in place adequate taste-masking techniques, if needed, which will lead to acceptable palatable formulations. Thus, there is an urgent need to develop and optimize taste assessment methods that could be used at different stages of the drug development process. The aim of this study was to investigate the suitability of the rat brief-access taste aversion (BATA) model as a screening tool for assessment of APIs aversiveness that could predict human taste responses. Presently, the taste intensity of nine marketed APIs known to have different levels of bitter intensity (quinine hydrochloride dihydrate, 6-n-propylthiouracil, sildenafil citrate, diclofenac sodium, ranitidine hydrochloride, caffeine citrate, isoniazid, telbivudine and paracetamol) was investigated at different overlapping concentrations with two in vivo taste assessment methods: the rat BATA model and human taste panels with the intention of determining the drugs' concentrations to produce half of the maximal rating. Overall there was a strong correlation (R2 = 0.896) between rats IC50 and humans EC50 values. This correlation verifies the BATA model as a rapid and reliable tool for quantitative assessment of API aversiveness. A comparable ranking order was obtained mainly for high and medium aversive compounds, whereas it was less aligned for weakly aversive compounds. It was nonetheless possible to propose a classification of poor taste intensity determined in rats that would predict human taste tolerability.

European Paediatric Formulation Initiative (EuPFI)-Formulating Ideas for Better Medicines for Children.

The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research and information dissemination. It brings together the capabilities of the industry, academics, hospitals, and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want.The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group have grown since its inception in 2007 and continue to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore, EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders have proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further research and identify issues that need more attention and analysis in the future.

Data for a pre-performance test of self-developed electronic tongue sensors.

This article presents data, which can be applied for a pre-performance test of self-developed electronic tongue sensors. Contained data is related to the research article "Impact of Sodium Lauryl Sulfate in oral liquids on E-Tongue Measurements" (http://dx.doi.org/10.1016/j.ijpharm.2016.10.045; (L.I. Immohr, R. Turner, M. Pein-Hackelbusch, 2016) [1]). Sensor responses were obtained from 10 subsequent measurements and four different concentrations of quinine hydrochloride by electronic tongue (TS-5000Z, Insent Inc., Atsugi-Shi, Japan) measurements. Based on the data for the pre-performance testing, which were calculated based on the fluctuation range of the sensor responses around the median, stability criteria and required preconditions cycles were defined.

Impact of sodium lauryl sulfate in oral liquids on e-tongue measurements.

During development of oral liquid medicines taste assessment is often required to evaluate taste and taste masking. Electronic tongue analysis can provide taste assessment of medicinal products but should only be conducted with medicines that interact with the instrument without damaging the sensor membranes or interfering with their electrical output so that robust data is generated. To explore the impact of a substance deemed unsuitable for electronic tongue analysis the influence of the anionic surfactant sodium lauryl sulfate (SLS), on the performance of the electronic tongue was conducted using electronic tongues equipped with self-developed PVC based sensors. The results showed a significant impact of SLS on all applied sensor types and an alteration of the sensor's sensitivity. Nevertheless, concentration dependent sensor responses could still be obtained and the sensor performance was not impacted negatively. Assessment of unsuitable substances should therefore be evaluated prior to performing electronic tongue analysis so that their impact is understood fully.

Towards the development of a paediatric biopharmaceutics classification system: Results of a survey of experts.

The aim of this research survey was to understand current global thinking around the need for and development of a paediatric biopharmaceutics classification system (pBCS) to be used for the development of paediatric medicines and regulatory purposes (e.g. Biowaivers). A literature review highlighted the paucity of data in this area and therefore a survey was developed to better understand this topic to identify areas of common thinking and highlight future research needs. Global experts in paediatric biopharmaceutics were identified from existing networks and public forums. An online survey was developed and circulated broadly to maximise participation. Sixty individuals (including academics, health care professionals, pharmaceutical industry scientists and regulators) completed the survey, bringing together their views on the need for a pBCS. The results highlighted that the area of greatest concern was the definition of BCS II and IV drugs within this population and additional research is required to generate evidence to underpin this issue. In questions relating to permeability and dissolution consensus was generally reached within the expert population suggesting that little additional research is required to define suitable criteria. More than 90% of those experts who participated agreed that a pBCS would be useful for paediatric populations with a greater need identified for the younger populations (newborn and infants compared to adolescents). The results presented will facilitate further discussion and research into the evidence to underpin a relevant pBCS. These results highlight the need for additional evidence and guidance in this area.

Playing hide and seek with poorly tasting paediatric medicines: do not forget the excipients.

The development of paediatric medicines can be challenging since this is a diverse patient population with specific needs. For example, the toxicity of excipients may differ in children compared to adults and children have different taste preferences. Acceptable palatability of oral paediatric medicinal products is of great importance to facilitate patient adherence. This has been recognised by regulatory authorities and so is becoming a key aspect of paediatric pharmaceutical development studies. Many active pharmaceutical ingredients (APIs) have aversive taste characteristics and so it is necessary to utilise taste masking techniques to improve the palatability of paediatric oral formulations. The aim of this review is to provide an overview of different approaches to taste masking APIs in paediatric oral dosage forms, with a focus on the tolerability of excipients used. In addition, where possible, the provision of examples of some marketed products is made.

The cerebellum in schizophrenia: a case of intermittent ataxia and psychosis--clinical, cognitive, and neuroanatomical correlates.

The contribution of cerebellar brain circuits to schizophrenia has been previously alluded to in the literature. This study examines current reappraisals of cerebellar involvement in cognition and behavior. An individual with documented developmental cerebellar anomalies who developed schizophrenic symptoms in late adolescence is described. Psychiatric, medical, and cognitive assessments were conducted to document the multifactorial contributions and manifestations of this dysfunction. Using this case as an example, the putative role of cerebellar dysfunction in the pathogenesis and clinical understanding of schizophrenic and psychotic illnesses is explored.