Hannah Batchelor

Patient-Centred Pharmaceutical Design to Improve Acceptability of Medicines: Similarities and Differences in Paediatric and Geriatric Populations

Patient acceptability of a medicinal product is a key aspect in the development and prescribing of medicines. Children and older adults differ in many aspects from the other age subsets of population and require particular considerations in medication acceptability. This review highlights the similarities and differences in these two age groups in relation to factors affecting acceptability of medicines. New and conventional formulations of medicines are considered regarding their appropriateness for use in children and older people. Aspects of a formulation that impact acceptability in these patient groups are discussed, including, for example, taste/smell/viscosity of a liquid and size/shape of a tablet. A better understanding of the acceptability of existing formulations highlights opportunities for the development of new and more acceptable medicines and facilitates safe and effective prescribing for the young and older populations.

Paediatric oral biopharmaceutics: key considerations and current challenges.

The complex process of oral drug absorption is influenced by a host of drug and formulation properties as well as their interaction with the gastrointestinal environment in terms of drug solubility, dissolution, permeability and pre-systemic metabolism. For adult dosage forms the use of biopharmaceutical tools to aid in the design and development of medicinal products is well documented. This review considers current literature evidence to guide development of bespoke paediatric biopharmaceutics tools and reviews current understanding surrounding extrapolation of adult methodology into a paediatric population. Clinical testing and the use of in silico models were also reviewed. The results demonstrate that further work is required to adequately characterise the paediatric gastrointestinal tract to ensure that biopharmaceutics tools are appropriate to predict performance within this population. The most vulnerable group was found to be neonates and infants up to 6 months where differences from adults were greatest.

Determination of formulation factors that affect oral medicines acceptability in a domiciliary paediatric population.

UNLABELLED Acceptability of medicines for children is a challenge, yet critical to ensure adherence to treatment. There is very little literature on formulation factors that influence acceptability of medicines, particularly in the domiciliary environment. This pragmatic study was conducted at University Hospital Coventry and Warwickshire (UHCW) with the aim of identifying the prevalence and nature of oral formulation-related barriers to medicines administration in children suffering from long-term conditions. This study used semi-structured face-to-face interviews with 221 parents/carers of children (0-18 years) and 57 young people (12-18 years). RESULT showed significant medicines refusal and manipulation in the domiciliary environment. Nearly one-third (71/232) of respondents reported medicines refusal. This was associated significantly with the age of child (p=0.016), socioeconomic status (IMD 2010 score) (p=0.002), taste (p<0.001), texture (p=0.017), and volume (of liquid/powder) or quantity (of solid dosage form) (p<0.001). 29% (74/252) of respondents reported manipulating medicines. P-values are based on multivariable statistical analysis models. This study has indicated that formulations prescribed to children with chronic conditions are not meeting the needs of a significant number of patients based on self-report. Age-appropriate medicines are required to provide suitable dose units with an acceptable taste for children. This study should aid pharmaceutical companies to prioritise paediatric formulation work.

Application of in vitro biopharmaceutical methods in development of immediate release oral dosage forms intended for paediatric patients.

Biopharmaceutics is routinely used in the design and development of medicines to generate science based evidence to predict in vivo performance; the application of this knowledge specifically to paediatric medicines development is yet to be explored. The aim of this review is to present the current status of available biopharmaceutical tools and tests including solubility, permeability and dissolution that may be appropriate for use in the development of immediate release oral paediatric medicines. The existing tools used in adults are discussed together with any limitations for their use within paediatric populations. The results of this review highlight several knowledge gaps in current methodologies in paediatric biopharmaceutics. The authors provide recommendations based on existing knowledge to adapt tests to better represent paediatric patient populations and also provide suggestions for future research that may lead to better tools to evaluate paediatric medicines.

Bioadhesive Dosage Forms for Esophageal Drug Delivery

No HeadingThe esophagus as a site for drug delivery has been much overlooked in comparison to the remainder of the gastrointestinal tract. The low permeability and transient nature of the esophagus means that it is unsuitable for delivery of drugs for systemic action. However, esophageal disorders including fungal infection, cancers, motility dysfunction, and damage due to gastric reflux may be treated using locally acting agents that offer benefits of reduced dosage and decreased side effects. Bioadhesive dosage forms that adhere to the esophageal mucosa and prolong contact have been investigated to improve the efficacy of locally acting agents. The rationale for local esophageal drug delivery and its limitations, the factors that determine adhesion to this organ, and the experimental models used in esophageal drug delivery research are reviewed.

Evidence of acceptability of oral paediatric medicines: a review

The aim of this review was to map the currently available evidence on acceptability of oral paediatric medicines to aid in the selection of suitable platform formulations for the development of new acceptable paediatric products.

Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis

Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery vehicles for an oral BCG vaccine in badgers.

Understanding the impact of media viscosity on dissolution of a highly water soluble drug within a USP 2 mini vessel dissolution apparatus using an optical planar induced fluorescence (PLIF) method.

In this study, planar induced fluorescence (PLIF) was used for the first time to evaluate variability in drug dissolution data using Rhodamine-6G doped tablets within small volume USP 2 apparatus. The results were compared with tablets contained theophylline (THE) drug for conventional dissolution analysis. The impact of hydrodynamics, sampling point, dissolution media viscosity and pH were investigated to note effects on release of these two actives from the hydrophilic matrix tablets. As expected mixing performance was poor with complex and reduced velocities at the bottom of the vessel close to the tablet surface; this mixing became even worse as the viscosity of the fluid increased. The sampling point for dissolution can affect the results due to in-homogenous mixing within the vessel; this effect is exacerbated with higher viscosity dissolution fluids. The dissolution profiles of RH-6G measured via PLIF and THE measured using UV analysis were not statistically different demonstrating that RH-6G is an appropriate probe to mimic the release profile of a highly soluble drug. A linear correlation was accomplished between the release data of the drug and the dye (R(2)>0.9). The dissolution profile of the dye, obtained with the analysis of the PLIF images, can be used in order to evaluate how the viscosity and the mixing performance of USP 2 mini vessel affect the interpretation of the dissolution data of the targeted drug.

Paediatric biopharmaceutics classification system: Current status and future decisions

Biopharmaceutical methods are routinely used in the design of medicines to predict in vivo absorption and hence guide the development of new products. Differences in anatomy and physiology of paediatric patients require adaptation of existing biopharmaceutical methods to ensure that in vivo predictions are relevant for this population. The biopharmaceutics classification system is a tool used in drug development to guide formulation selection and manufacture from early clinical studies through to product launch. The applicability of the biopharmaceutics system to paediatric product development has yet to be explored; this note brings together some key issues in direct extrapolation from adults into paediatric populations.

The Importance of a Mathematics Diagnostic Test for Incoming Pharmacy Undergraduates

The expansion of higher education in the UK in the 1980s and the subsequent increase in student numbers has created greater variation in cohorts of students entering university. Entry requirements are more relaxed and students with lower pre-university (A-level) qualifications or alternative qualifications (BTEC, GNVQ) are routinely accepted onto MPharm degree programmes within the UK. Mathematics is a key component in the pharmacy degree programme and an understanding of basic mathematics is essential. This wide variation in mathematical ability coupled with increasing class sizes has led to various strategies being introduced to ensure that all students attain the required level of mathematical ability to complete the degree programme. This study investigates the use of a diagnostic test to improve both the teaching and learning experience. The paper describes an investigation into what may be learnt about students’ background knowledge and skills from initial assessment and information about their prior qualifications, and how this information may be used to devise effective teaching and learning strategies.