Mine Orlu

Patient acceptability of 3D printed medicines

Patient-centric medicine is a derivative term for personalised medicine, whereby the pharmaceutical product provides the best overall benefit by meeting the comprehensive needs of the individual; considering the end-user from the beginning of the formulation design process right through development to an end product is a must. One way in which to obtain personalised medicines, on-site and on-demand is by three-dimensional printing (3DP). The aim of this study was to investigate the influence of the shape, size and colour of different placebo 3D printed tablets (Printlets™) manufactured by fused deposition modelling (FDM) 3DP on end-user acceptability regarding picking and swallowing. Ten different printlet shapes were prepared by 3DP for an open-label, randomised, exploratory pilot study with 50 participants. Participant-reported outcome (PRO) and researcher reported outcome (RRO) were collected after picking and swallowing of selected printlet geometries including sphere, torus, disc, capsule and tilted diamond shapes. The torus printlet received the highest PRO cores for ease of swallowing and ease of picking. Printlets with a similar appearance to conventional formulations (capsule and disc shape) were also found to be easy to swallow and pick which demonstrates that familiarity is a critical acceptability attribute for end-users. RRO scores were in agreement with the PRO scores. The sphere was not perceived to be an appropriate way of administering an oral solid medicine. Smaller printlet sizes were found to be preferable; however it was found that the perception of size was driven by the type of shape. Printlet colour was also found to affect the perception of the end-user. Our study is the first to guide the pharmaceutical industry towards developing patient-centric medicine in different geometries via 3DP. Overall, the highest acceptability scores for torus printlets indicates that FDM 3DP is a promising fabrication technology towards increasing patient acceptability of solid oral medicines.

Orodispersible Films: Towards Drug Delivery in Special Populations

Orodispersible films (ODF) hold promise as a novel delivery method, with the potential to deliver tailored therapies to different patient populations. This article reviews the current strides of ODF technology and some of its unmet quality and manufacturing aspects. A topic highlights opportunities and limitations of inkjet printed ODF as a population-specific drug delivery. Overall, this article aims to stimulate further research to fill the current knowledge gap between manufacturing and administration requirements of ODF targeting specific patient subpopulations such as geriatrics.

Acceptability of placebo multiparticulate formulations in children and adults

Patient acceptability is an important consideration in the design of medicines for children. The aim of this study was to investigate acceptability of multiparticulates in healthy children and adults. A randomised, single-blind acceptability testing was performed involving 71 children (4–12 years) and 61 adults (18–37 years). Each participant received three 500 mg samples of microcrystalline cellulose pellets administered on a medicine spoon with water at 5–10 minutes intervals. Acceptability was measured based on voluntary intake of the samples, facial expressions, ratings on hedonic scales and reported willingness to take multiparticulates everyday as a medicine. Multiparticulates were voluntarily swallowed by 92% of children and 100% of adults. However, palatability issues were identified, with emphasis on textural aspects. Grittiness perception received negative ratings on hedonic scales by 60% of children and 51% of adults. Researcher observations revealed that 72% of children and 42% of adults displayed negative facial expressions towards the samples. Children reported their willingness to take multiparticulates as a medicine in 30% of the cases, compared to 74% in adults. This study demonstrates that multiparticulates may be a suitable formulation platform for children and adults, although palatability concerns have been highlighted. Additional work is required to define acceptability criteria and to standardise methodologies.

Acceptability of orodispersible films for delivery of medicines to infants and preschool children

Abstract Orodispersible films (ODFs) possess potential to facilitate oral drug delivery to children; however, documentation of their acceptability in this age group is lacking. This study is the first to explore the initial perceptions, acceptability and ease of use of ODFs for infants and preschool children, and their caregivers through observed administration of the type of dosage form. Placebo ODFs were administered to children stratified into aged 6 to 12 months, 1 year, 2 years, 3 years, 4 years and 5 years old and into those with an acute illness or long-term stable condition in hospital setting. Acceptability of the dosage form and end-user views were assessed by (a) direct observation of administration, (b) questionnaires to caregivers and nurses, and (c) age-adapted questionnaires for children aged 3 years and over. The majority of children (78%) aged 3 years and over gave the ODF a positive rating both on verbal and non-verbal scales. Despite little prior experience, 78% of caregivers expressed positive opinion about ODFs before administration. After the ODFs were taken, 79% of infant caregivers and 86% caregivers of preschool children positively rated their child’s acceptance of the ODF. The intraclass correlation coefficient value was 0.92 showing good agreement between ratings of caregivers and nurses. ODFs showed a high degree of acceptability among young children and their caregivers. If drug loading permits, pharmaceutical companies should consider developing pediatric medicines in this format. The methodology described here is useful in assessing the acceptability of active ODF preparations and other dosage forms to children.

CHAPTER 10:Paediatric Pharmaceutics—The Science of Formulating Medicines for Children

Paediatrics (also spelled pediatrics) deals with the medical care of neonates, infants, children, and adolescents, from birth up to 18 years of age. Child health is key to overall human life expectancy, as paediatric diseases may have a lifelong effect on quality of life. On a global scale nearly 5.8 million children under the age of five died in 2015, representing a 52% decline in the number of under-five deaths since 1990. Neonatal deaths fell at a slower pace since 1990, decreasing 42% to 2.6 million; stillbirths declined 47% to 2.1 million. Although life expectancy has improved around the world between 1990 and 2015, it still remains the case that people in more developed countries can look forward to longer and healthier lives than people in less developed countries. One of the factors driving the increases in life expectancy at birth is better health outcomes for young children, implying urgent need for medicines that keep children healthy. Children have the right to access medicines that are appropriate to their unique needs and to have adequate assurance of their quality, safety and efficacy. This has been widely acknowledged on a worldwide platform and prompted global initiatives and legislative changes that have transformed this once niche area into an integral part of the drug development process. This chapter discusses the specific needs of children, how the implementation of paediatric regulations has influenced/promoted the research into this previously neglected population and key attributes to consider during the designing and development of paediatric dosage forms to provide adequate paediatric therapies.

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells.

Electrosprayed microparticles for intestinal delivery of prednisolone

Single and coaxial electrospraying was used to prepare Eudragit L100-55 polymer microparticles containing prednisolone as the active pharmaceutical ingredient. Different compositions of prednisolone and Eudragit L100-55 were used to develop five different formulations with different polymer : drug ratios. The resultant microparticles had a toroidal shape with a narrow size distribution. Prednisolone was present in an amorphous physical state, as confirmed by X-ray diffraction analysis. Dissolution studies were carried out in order to investigate the feasibility of the proposed system for site-specific release of prednisolone. The release rates were interpreted in terms of diffusion-controlled release. It was shown that utilization of pH-responsive Eudragit L100-55 could minimize the release of prednisolone in the acidic conditions of the stomach, which was followed by rapid release as the pH of the release medium was adjusted to 6.8 after the first 2 h. This is especially desirable for the treatment of conditions including inflammatory bowel disease and colon cancer.

Educational potential of using virtual patients for promoting interprofessional learning between medical and pharmacy students: A qualitative study

ABSTRACT Interprofessional learning (IPL), involving various professions within healthcare, has been proven to improve the quality of patient care by encouraging collaboration between professionals. Careful consideration of appropriate educational tools and content is required in order to facilitate the effective IPL. This study aimed to explore medical and pharmacy students’ preconceptions of the role of virtual patients (VPs) as a learning tool for IPL within their education. A secondary aim was to elicit feedback to inform the development of new VP cases. Two focus groups (one with medical students and the other with pharmacy students), consisting of six students in each, were recruited. Participant perceptions regarding VP-based IPL were explored. Data were analysed using a thematic approach. Participants thought that there were some potential learning benefits of using VPs as part of their curriculum. Pharmacy students held increased value in VPs due to their limited access to patients during their education. Medical students challenged the role of VPs in their clinical development and concerned that VPs lack the flexibility required by doctors to use their judgement and work with uncertainty. Limited understanding of team members’ roles in patient care and self-reported ignorance of the overlap in curricula appear to be key barriers for students in valuing the knowledge base of each other’s profession and possible benefits of using VPs in joint learning. This study generated a number of key implications which need to be considered when introducing VP-based IPL.

Electrospun fixed dose formulations of amlodipine besylate and valsartan

Graphical abstract Figure. No Caption available. Abstract Increasing numbers of elderly people require multi‐drug therapies. One route to improve adherence rates is to prepare fixed dose combinations (FDCs), in which multiple active ingredients are loaded into a single formulation. Here, we report the use of electrospinning to prepare fast‐dissolving oral FDCs containing amlodipine besylate and valsartan, two drugs prescribed as FDCs for the treatment of hypertension. Electrospun fibers were prepared loaded with one or both drugs, using polyvinylpyrrolidone as the polymer matrix. The fibers were largely cylindrical in morphology and comprise amorphous solid dispersions except with the highest loadings of amlodipine besylate. HPLC demonstrated drug entrapment efficiencies of >85% of the theoretical dose. The mats have folding endurances and thicknesses suitable for use as oral films. The amlodipine besylate‐loaded systems are fast‐dissolving, with >90% release obtained within 120 s. In contrast, valsartan release from its single‐drug formulations took longer, ranging from 360 s to 24 min. With the FDC formulations, rapid release within 360 s was achieved when the loading was 5% w/w of each drug, but again the release time increased with drug loading. Electrospun fibers therefore have significant promise as FDCs, but the target drug and its loading need to be carefully considered.

The effect of administration media on palatability and ease of swallowing of multiparticulate formulations

Graphical abstract Figure. No Caption available. ABSTRACT Multiparticulate formulations based on pellets, granules or beads, could be advantageous for paediatrics, geriatrics and patients with swallowing difficulties. However, these formulations may require suitable administration media to facilitate administration. The aim of this work was to investigate the effect of administration media properties on palatability and ease of swallowing of multiparticulates. A range of vehicles were developed using xanthan gum (XG) and carboxymethyl cellulose (CMC) as model hydrocolloids. Such vehicles were prepared at three consistency levels (Level 1 – ‘syrup’, Level 2 – ‘custard’ and Level 3 – ‘pudding’) to investigate the effect of viscosity on their performance as administration media. A randomised, single‐blind sensory evaluation study was carried out in thirty healthy adult volunteers using microcrystalline cellulose pellets as model multiparticulates, dispersed in the hydrogels (and water as control) at a concentration of 250 mg in 5 ml. Samples were evaluated using 5‐point scales. The use of hydrogels as administration media improved a range of sample attributes compared to water formulations, including appearance, taste, mouthfeel, ease of swallowing and residue in the mouth (all improved by ca. 0,5 points) and oral grittiness perception (improved by ca. 1 point). Polymeric hydrogels thickened to medium consistency (Level 2, XG 0.5% and CMC 1.0% w/v) demonstrated the best performance.