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Accurate dosing of the right medicine to the right patient is a key element of safe and efficacious pharmacotherapy, yet prone to technical challenges and human error when dosing involves the administration of small volumes of liquid medicines. For this reason, the topic has gained increased attention over the last decade from multiple stakeholder parties e.g. academia, hospital pharmacy, the medical device and pharmaceutical industry, and regulatory agencies. It is now well acknowledged that spoons and cups are not suitable for the measurement of small volumes of oral liquid medicines and that syringes are a better alternative, but syringes for parenteral use should not be used for oral dosing in order to avoid accidental parenteral delivery of oral products. However, dosing accuracy of very small volumes of liquid medicines to young children, and especially pre-term neonates, is still not sufficiently ensured. A workshop was organised in 2018 by the European Paediatric Formulation Initiative to reflect on current status and challenges (first part) and possible strategies to improve the present situation (second part). A voting system (n = 24) was used to consider the most favourable solutions. The harmonisation and/or standardisation of the technical design of oral syringes (including e.g. female/male connection) was considered a key priority.

Patients play an important role in achieving the desired therapeutic outcomes, as they are frequently responsible for their own medication management. To facilitate drug administration and overcome medication issues, the patients’ needs and preferences should be considered in the pharmaceutical drug product design. With the aim to evaluate the current state of evidence for patient appropriateness, acceptability, usability and preference for aspects of this design, a literature search was performed. Comparative clinical studies that assessed such endpoints for different patient populations were included and summarized descriptively. The search identified 45 publications that met the inclusion criteria. A detailed analysis of the studies identified two main areas investigating either packaging design ( n = 10) or dosage form design ( n = 35). Studies on packaging design showed preferences for wing top and screw cap openings, push-through blisters and suppositories with slide system. Additionally, child-resistant containers should be avoided concerning specific patient populations. Regarding dosage form design, sprinkles and minitablets were the most preferred in studies involving young patients, while preferences varied considerably depending on route of administration and geographical region in studies with adult patients. Review of the methodology used in the studies revealed that ten studies had used well-defined protocols and observational endpoints to investigate patient appropriateness. Studies focusing on methodology for testing the appropriateness and usability of drug products by patients were not found. In conclusion, more interdisciplinary scientific efforts are required to develop and increase research in understanding patient needs and preferences.

AIMS: Medication safety requires urgent attention in hospital pharmacy. This study evaluated the medication-related problems/errors as reported to the Dutch medication incident registry and disseminated for information to pharmacists. Through analysis by an expert panel we aimed to better understand which problems could have been mitigated by the drug product design. Additionally, the (wider) implications of the problems for current hospital/clinical practice were discussed.METHODS: Items were extracted from the public Portal for Patient Safety. Items were included if relevant for older people and connected with the drug product design and excluded if they should reasonably have been intercepted by compliance to routine controls or well-known professional standards in pharmaceutical care. To explore any underreporting of well-known incidents, it was investigated if different medication-related problems could be observed in a regional hospital practise over a 1-month period. For 6 included items (cases), the implications for hospital/clinical practise were discussed in an expert panel.RESULTS: In total, 307 items were identified in the Portal for Patient Safety; all but 14 were excluded. Six cases were added from daily hospital practice. These 20 cases commonly related to confusing product characteristics, packaging issues such as the lack of a single unit package for an oncolytic product, or incorrect or incomplete user instructions.CONCLUSION: Medication registries provide important opportunities to evaluate real-world medication-related problems. However, underreporting of well-known problems should be considered. The product design can be used as an (additional) risk mitigation measure to support medication safety in hospital practice.

The aging population and the growing multimorbidity of the major patient population as well as the advanced (pharmaco)therapeutic treatment options are increasing the complexity of independent drug therapy management and administration. The increased complexity may have an impact on drug adherence (including any need for patients initiated coping strategies), and consequently on the safety and efficacy of the medicine. To overcome adherence issues caused by the design of the medicine, it is crucial that developers consider the age appropriateness of the medicine (route of administration, dosage form, excipients in the composition, frequency of dosing) in meeting patients’ needs to manage their therapy without the support of a care giver. In order to understand the scientific evidence on such age appropriately designed medicines for use by older adults, a literature search was performed in the Medline database (all languages included). The search produced 34 publications that met the inclusion and exclusion criteria for the patient population of 65 years an older. An in-depth analysis of the included publications with respect to the methodological quality (study design, data collection, endpoints chosen) and results showed that none of these publications had adequately investigated the age appropriateness of the medicine for use by older adults. The authors consider that the knowledge gap in this area requires attention of all stakeholders in the healthcare community.

Objective Liquid medicines are easy to swallow. However, they may have disadvantages, such as a bad taste or refrigerated storage conditions. These disadvantages may be avoided by the use of oral solid medicines, such as powders or tablets. The aim of this study was to investigate the acceptability of and preference among four oral formulations in domiciliary infants and preschool children in The Netherlands. Methods Parents administered four oral placebo dosage forms that were aimed at a neutral taste, at home, to their child (1–4 years of age) twice on one day following a randomised cross-over design: small (4 mm) tablet, powder, suspension and syrup. They were asked to report the child's acceptability by a score on a 10 cm visual analogue scale (VAS score) and by the result of the intake. At the end of the study, they were asked to report the preference of the child and themselves. Results 183 children were included and 148 children were evaluated. The data revealed a period/cross-over effect. The estimate of the mean VAS score was significantly higher for the tablet than for the suspension (tablet 9.39/9.01; powder 8.84/8.20, suspension 8.26/7.90, syrup 8.35/8.19; data day 1/all days). The estimate of the mean number of intakes fully swallowed was significantly higher for the tablet than for the other formulations (all p values

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Children are entitled to safe, efficacious, child and parent friendly (i.e. age-appropriate) medicines. However, off-label and unlicensed paediatric prescription rates in hospital range from 36% (surgical and medical wards) to 93% (neonatal wards), which indicates a general lack of age-appropriate medicines for children. In 2007, the European Union issued the Paediatric Regulation aiming at better medicines for children by, for example, increasing the number of authorized paediatric medicines. WHAT THIS STUDY ADDS • This study reviews the availability and age-appropriateness of medicines for children in the Netherlands, herewith providing a baseline for an estimation of the effect of the European Paediatric Regulation in the near future. This study also provides a tool for the evaluation of the child authorization status of medicines on the basis of the information in the Summary of Product Characteristics (SPC) and for the assessment of key aspects of the age-appropriateness of paediatric formulations. AIM To study the number of medicines and active chemical entities that are authorized and commercially available for children in the Netherlands and to evaluate the age-appropriateness of the available paediatric medicines. METHODS The availability of paediatric medicines and active chemical entities was studied with the help of a Dutch medicines database and the Summary of Product Characteristics. Medicines were categorized with respect to their route of administration, type of oral dosage form and therapeutic category. The age-appropriateness was assessed on three aspects: dose capability, suitability of the dosage form and inclusion of potentially harmful excipients. RESULTS Three thousand five hundred and forty-two paediatric medicines containing 703 different active chemical entities were identified. This equalled half of all the medicines and chemical entities available for human use. The percentage of paediatric medicines increased with age and varied for the route of administration from 22% (dermal) to 81% (inhalation) and for the therapeutic category from 11% (uro-genital, sex hormones) to 89% (anti-parasites). The appropriateness of the paediatric medicines with respect to their authorization status, dose capability and dosage form increased with age from 27–88%. Fifty-two percent of all oral paediatric liquid formulations contained a potentially harmful excipient. CONCLUSION This study confirms the limited availability of paediatric medicines for a broad range of therapeutic areas and shows that paediatric medicines may not be age-appropriate, even if authorized. While confirming the need for a legislative incentive, the results also provide baseline information for an estimation of the effect of the European Paediatric Regulation in the near future.

In view of the high rates of off-label and unlicensed prescribing of drugs in children, the US Food and Drug Administration and the European Union have implemented legislative regulations for the pharmaceutical industry to increase the number of drugs with approved pediatric labeling. However, the extent to which the effects of pharmaceutical technologic aspects of pediatric oral drugs (eg, taste, route and frequency of administration, user instructions) on patient-related outcomes (eg, efficacy, tolerability, preference, adherence) can be based on clinical evidence from the available literature is unknown.This systematic literature review aimed to identify the nature, volume, and quality of comparative studies that have assessed the effects of pharmaceutical technologic aspects of oral pediatric drugs on patient-related outcomes.The Cochrane, EMBASE, and MEDLINE databases were searched from their start through December 31, 2009. Studies were eligible for inclusion if they were published in English; included search terms for child, study design, medicine, formulation aspects, dosage form, routes of administration, patient acceptance, adherence, side effects and tolerability, and/or efficacy; reported onor = 10 children aged 0 to18 years; and described the effects ofor = 1 of 3 pharmaceutical technologic aspects of an oral pediatric drug (formulation and dosage form; route and frequency of administration; and/or packaging, administration device, and user instruction) onor = 1 of 6 patient-related outcomes (clinical efficacy, side effects and tolerability, patient preference, patient acceptance, administration errors, and/or adherence). Studies were excluded if they concerned a nonallopathic drug (ie, homeopathic remedy, anthroposophic drug, herbal supplement, or food supplement); related to asthma (because modern asthma treatment protocols strongly favor the use of drug inhalation above oral medication); and/or related to analgesics. The characteristics of each of the included publications were assessed with respect to pharmaceutical technologic aspect studied; patient-related outcomes studied; pharmacotherapeutic indication; year of publication; geographic location; number and age of the included subjects; and sponsorship by industry and/or author affiliation with the pharmaceutical industry. The electronic search was supplemented with a manual search of the cited references.Ninety-four publications were identified as eligible for inclusion. These publications reported on 176 assessments of the effects ofor = 1 pharmaceutical technologic aspect onor = 1 patient-related outcome. Fifty-five percent of the studies were conducted in children aged 2 or 3 years, and 69% in children aged 4 or 5 years. Forty-three percent of the publications includedor = 100 patients. Fifty-one percent of the studies were conducted in the United States or Canada, and 29% in Europe. Antibacterials for systemic use were the subject of 30% of the included publications. Two of the 94 publications were of appropriate methodologic quality (Jadad scoreor = 4). Forty-nine percent of the studies were sponsored by the pharmaceutical industry or were written byor = 1 author affiliated with the industry. Sixty-eight percent of the included studies had Jadad scores of 0 or 1 (poor quality). The proportion of industry-sponsored or industry-authored studies with a Jadad scoreor = 2 or inor = 100 children was not significantly different from that of non-industry-sponsored or-authored studies. The proportion of industry-sponsored or industry-authored studies conducted in the United States/Canada (48 [51%]) was not significantly different from that of studies conducted elsewhere (46 [49%]). The distribution of technologic aspects assessed in the included studies were formulation and dosage form, 48%; route and frequency of administration, 44%; and packaging, administration device, and user instruction, 8%. Seventy-six assessments includedor = 100 patients. Twenty-one of these assessments addressed patient acceptance or patient preference; 17, clinical efficacy; and 14, side effects and tolerability.This systematic review identified 94 articles on oral drugs for use in children and adolescents, which reported on a total 176 assessments of the effects of 3 pharmaceutical technologic aspects (formulation and dosage form; route and frequency of administration; and packaging, administration device, and user instruction) on 6 patient-related outcomes (clinical efficacy, side effects and tolerability, patient preference, patient acceptance, administration errors, and adherence). Only 2 of the 94 publications were of appropriate methodologic quality. These results suggest that published clinical evidence to support pharmaceutical development programs is limited.

The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

Item does not contain fulltext This letter is a response to the comments of Kalleian Eserian et al. on our study relating to the accuracy, precision and sustainability of six tablet splitters and a kitchen knife as an alternative to breaking paracetamol 500mg tablets by hand. We would like to inform the readers of International Journal of Pharmaceutics that our study focused on splitting tablets with a mechanical tool rather than breaking tablets by hand. Although publications on hand breaking tablets were not cited for this reason, we are familiar with the conclusions of these publications. This is especially true for the publications that were written by direct colleagues from the department of the corresponding author e.g., Van Santen et al. and Van der Steen et al.

Contains fulltext : 136106.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Tablets are frequently subdivided to lower the dose, to facilitate swallowing by e.g. children or older people or to save costs. Splitting devices are commonly used when hand breaking is difficult or painful. METHODS: Three techniques for tablet subdivision were investigated: hand breaking, tablet splitter, kitchen knife. A best case drug (paracetamol), tablet (round, flat, uncoated, 500 mg) and operator (24-year student) were applied. Hundred tablets were subdivided by hand and by three devices of each of the following types: Fit & Healthy, Health Care Logistics, Lifetime, PillAid, PillTool, Pilomat tablet splitter; Blokker kitchen knife. The intra and inter device accuracy, precision and sustainability were investigated. The compliance to (adapted) regulatory requirements was investigated also. RESULTS: The accuracy and precision of hand broken tablets was 104/97% resp. 2.8/3.2% (one part per tablet considered; parts right/left side operator). The right/left accuracies of the splitting devices varied between 60 and 133%; the precisions 4.0 and 29.6%. The devices did not deteriorate over 100-fold use. Only hand broken tablets complied with all regulatory requirements. CONCLUSION: Health care professionals should realize that tablet splitting may result in inaccurate dosing. Authorities should undertake appropriate measures to assure good function of tablet splitters and, where feasible, to reduce the need for their use.

Ageing comes with an increased propensity in the alteration of human organ and body functions, which can e.g. result in multi-morbidity, frailty, polypharmacy, altered medication safety and/or efficacy, and problems with the practical use of medicines in a real world setting. Such problems may e.g. involve difficulties opening containers, swallowing large tablets, breaking tablets by hand, or correctly understanding the user instruction. This review aims to summarize the European regulatory activities towards better medicines for older people, with a main focus on formulation development and the overall drug product design. It addresses the ICH E7 guideline “Studies in support of special populations, geriatrics”, the ICH Q8 guideline “Pharmaceutical development”, the EMA good practice guide on “Risk minimisation and prevention of medication errors” and the forthcoming EMA CHMP QWP reflection paper on the “Quality aspects (pharmaceutical development) of medicines for older people”. In addition, three key aspects to the practical use of medicines by older people are discussed in a wider context: multi-particulates including small tablets (also referred to as mini-tablets), ease of opening and storage conditions. Furthermore, attention is paid to work in progress e.g. incentives by the European national drug regulatory authorities, and patient centric drug product development.