The development and evaluation of an evidence-based drug information service

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Paediatric drug development:reformulation, in vitro, genomic and in vivo evaluation

Angiotensin converting enzyme (ACE) inhibitors lisinopril and ramipril were selected from EMA/480197/2010 and the potassium-sparing diuretic spironolactone was selected from the NHS specials list for November 2011 drug tariff with the view to produce oral liquid formulations providing dosage forms targeting paediatrics. Lisinopril, ramipril and spironolactone were chosen for their interaction with transporter proteins in the small intestine. Formulation limitations such as poor solubility or pH sensitivity needed consideration. Lisinopril was formulated without extensive development as drug and excipients were water soluble. Ramipril and spironolactone are both insoluble in water and strategies combating this were employed. Ramipril was successfully solubilised using low concentrations of acetic acid in a co-solvent system and also via complexation with hydroxypropyl-β-cyclodextrin. A ramipril suspension was produced to take formulation development in a third direction. Spironolactone dosages were too high for solubilisation techniques to be effective so suspensions were developed. A buffer controlled pH for the sensitive drug whilst a precisely balanced surfactant and suspending agent mix provided excellent physical stability. Characterisation, stability profiling and permeability assessment were performed following formulation development. The formulation process highlighted current shortcomings in techniques for taste assessment of pharmaceutical preparations resulting in early stage research into a novel in vitro cell based assay. The formulations developed in the initial phase of the research were used as model formulations investigating microarray application in an in vitro-in vivo correlation for carrier mediated drug absorption. Caco-2 cells were assessed following transport studies for changes in genetic expression of the ATP-binding cassette and solute carrier transporter superfamilies. Findings of which were compared to in vitro and in vivo permeability findings. It was not possible to ascertain a correlation between in vivo drug absorption and the expression of individual genes or even gene families, however there was a correlation (R2 = 0.9934) between the total number of genes with significantly changed expression levels and the predicted human absorption.

Development and psychometric evaluation of a new team effectiveness scale for all types of community adult mental health teams:a mixed-methods approach

Defining 'effectiveness' in the context of community mental health teams (CMHTs) has become increasingly difficult under the current pattern of provision required in National Health Service mental health services in England. The aim of this study was to establish the characteristics of multi-professional team working effectiveness in adult CMHTs to develop a new measure of CMHT effectiveness. The study was conducted between May and November 2010 and comprised two stages. Stage 1 used a formative evaluative approach based on the Productivity Measurement and Enhancement System to develop the scale with multiple stakeholder groups over a series of qualitative workshops held in various locations across England. Stage 2 analysed responses from a cross-sectional survey of 1500 members in 135 CMHTs from 11 Mental Health Trusts in England to determine the scale's psychometric properties. Based on an analysis of its structural validity and reliability, the resultant 20-item scale demonstrated good psychometric properties and captured one overall latent factor of CMHT effectiveness comprising seven dimensions: improved service user well-being, creative problem-solving, continuous care, inter-team working, respect between professionals, engagement with carers and therapeutic relationships with service users. The scale will be of significant value to CMHTs and healthcare commissioners both nationally and internationally for monitoring, evaluating and improving team functioning in practice.

Paediatric drug development of ramipril:reformulation, in vitro and in vivo evaluation

Ramipril is used mainly for the treatment of hypertension and to reduce incidence of fatality following heart attacks in patients who develop indications of congestive heart failure. In the paediatric population it is used most commonly for the treatment of heart failure, hypertension in type 1 diabetes and diabetic nephropathy. Due to the lack of a suitable liquid formulation, the current study evaluates the development of a range of oral liquid formulations of ramipril along with their in vitro and in vivo absorption studies. Three different formulation development approaches were studied: solubilisation using acetic acid as a co-solvent, complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) and suspension development using xanthan gum. Systematic optimisation of formulation parameters for the different strategies resulted in the development of products stable for twelve months at long term stability conditions. In vivo evaluation showed CMAX of 10.48 µg/mL for co-solvent, 13.04µg/ml for the suspension and 29.58µg/mL for the cyclodextrin based ramipril solution. Interestingly, both ramipril solution (co-solvent) and the suspension showed a TMAX of 2.5h, however, cyclodextrin based ramipril produced TMAX at 0.75h following administration. The results presented in this study provide translatable products for oral liquid ramipril which offer preferential paediatric use over existing alternatives.

The Birmingham relationship continuity measure:the development and evaluation of a measure of the perceived continuity of spousal relationships in dementia

Background: Qualitative research has suggested that spousal carers of someone with dementia differ in terms of whether they perceive their relationship with that person as continuous with the premorbid relationship or as radically different, and that a perception of continuity may be associated with more person-centered care and the experience of fewer of the negative emotions associated with caring. The aim of the study was to develop and evaluate a quantitative measure of the extent to which spousal carers perceive the relationship to be continuous. Methods: An initial pool of 42 questionnaire items was generated on the basis of the qualitative research about relationship continuity. These were completed by 51 spousal carers and item analysis was used to reduce the pool to 23 items. The retained items, comprising five subscales, were then administered to a second sample of 84 spousal carers, and the questionnaire's reliability, discriminative power, and validity were evaluated. Results: The questionnaire showed good reliability: Cronbach's α for the full scale was 0.947, and test-retest reliability was 0.932. Ferguson's δ was 0.987, indicating good discriminative power. Evidence of construct validity was provided by predicted patterns of subscale correlations with the Closeness and Conflict Scale and the Marwit-Meuser Caregiver Grief Inventory. Conclusion: Initial psychometric evaluation of the measure was encouraging. The measure provides a quantitative means of investigating ideas from qualitative research about the role of relationship continuity in influencing how spousal carers provide care and how they react emotionally to their caring role. © 2012 International Psychogeriatric Association.