Characterisation of an in Vitro Aged Cell Culture Model

The present study aims to provide a detailed protocol to obtain an aged cell culture model, which is conveniently characterised in terms of morphology, metabolism, and key biochemical markers of senescence. Commercial Human Dermal Fibroblasts (HDF) (67-year-old female Asian donor) were cultured over a span of 35 passages to determine at what passages they express the phenotypes found in vivo in the geriatric population. The growth rate and density (counting, Trypan Blue) at confluence declined 4- and 3-fold, respectively. During 15 passages in vitro ageing the fibroblast metabolic capacity (XTT) was heavily reduced (by 75%), while conversely the content of cellular proteins (SRB) slightly increased (2 fold). Senescent cells (SA-β-gal positive) were continuously emerging from 0 to 20%. Freezing/thawing at this stage restored metabolic performance to original values which declined at a similar rate as before. Passages 5 - 10 of our selected aged HDFs were found to mimic in vivo tissue of older adults to the greatest extent

Patient centric formulations for paediatrics and geriatrics: Similarities and differences

Paediatrics and geriatrics both represent highly heterogenous populations and require special consideration when developing appropriate dosage forms. This paper discusses similarities, differences and considerations with respect to the development of appropriate medicine formulations for paediatrics and geriatrics. Arguably the most significant compliance challenge in older people is polypharmacy, whereas for children the largest barrier is taste. Pharmaceutical technology has progressed rapidly and technologies including FDCs, multi-particulates and orodispersible dosage forms provide unprecedented opportunities to develop novel and appropriate formulations for both old and new drugs. However, it is important for the formulation scientists to work closely with patients, carers and clinicians to develop such formulations for both the paediatric and geriatric population

Investigation into the dosage form attributes of currently UK licensed cardiovascular and Parkinson's disease drug products

Globally, there is a continuous rise in the older population (over 65 years), particularly in developed countries. As many diseases are age-related, older adults represent a highly heterogeneous cohort. This presents a major challenge for both the pharmaceutical industry and healthcare professionals. The purpose of this research was to attract attention towards the appropriateness of geriatric formulations by investigating the dosage form attributes of currently UK licensed cardiovascular and Parkinson's disease drug products. Medication available in the UK for cardiovascular disorders and Parkinson's disease were screened and the available formulations, packaging and patient information leaflets of these medicines were analysed, with the goal of raising awareness of the need to cater for elderly patients with increasing difficulty in managing their medication. It emerged that although cardiovascular disorders and Parkinson's disease are more prevalent in older people, many treatment options have not been optimised for this cohort. In particular, older patient centred dosage forms, specific dosing requirements, excipients, patient-friendly packaging and easy-to-follow patient information were highlighted as areas to be considered in order to optimise health outcomes in the ageing population

Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project

Characterisation of rectal amoxicillin (RAMOX) for the treatment of pneumonia in children

Access to medicines, including their availability and affordability, is a major public health challenge worldwide. This research aimed to characterise rectal formulations containing amoxicillin for the treatment of pneumonia in children under five, as an accessible alternative to existing formulations. Lipophilic Suppocire (S-NA15) and hydrophilic polyethylene glycol (PEG; 80% PEG 1500 and 20% PEG 4000, w/w) suppositories containing 250 mg amoxicillin were prepared. Hardness, apparent viscosity, uniformity of mass, uniformity of content, disintegration and dissolution time were determined. Irritation potential was screened using a slug mucosal assay and antibacterial efficacy against Staphylococcus aureus determined by isothermal microcalorimetry. Both lipophilic and hydrophilic formulations met the European Pharmacopoeia standards for suppositories when tested in vitro. They disintegrated within 30 min with rapid amoxicillin release profiles (98.6 ± 0.9%, 94.9 ± 1.2% over 30 min, respectively). Over-encapsulation of S-NA15 suppositories with hydroxypropyl methylcellulose shells slowed drug release and improved stability over 2 months. S-NA15 suppositories were classified as non-irritant and PEG suppositories only mildly irritant. Antibacterial efficacy of formulations was equivalent to amoxicillin alone. Both PEG and over-encapsulated S-NA15 rectal formulations developed in the present work have shown promise based on pre-clinical screening, and further development is justified to develop a product with commercial potential

The rectal route of medicine administration for children: Let's get to the bottom of it!

Aims: Research around paediatric rectal drug delivery has previously been based on views of parents and healthcare workers. The aim of this exploratory study was to gauge whether children and young adults in the UK were comfortable with the idea of rectal drug delivery. / Methods: Eleven children from a pre-existing patient and public advisory group were involved in the session. Rectal drug delivery was explained and group participants were asked a series of questions. Responses were discussed in a group and recorded individually. /Results: Of the group, 27% would consider the rectal route, while 64% said it depended on other options available. The primary concern focused on potential for abusive misuse by others. Participants thought this would be overcome if the child could self-administer, although there was also concern about the process of self-administration. / Conclusions: Not all children in the UK are against rectal drug delivery, but education is needed to teach children to self-administer medication in this way

A mini-review of non-parenteral clonidine preparations for paediatric sedation

OBJECTIVE: To provide an overview of non-parenteral clonidine formulations and assess the feasibility of their use for paediatric sedation. / METHODS: A literature search was conducted using electronic databases and a combination of search terms. Forty articles met the inclusion criteria. Publications were grouped into different dosage forms and assessed for their potential application for sedation of children in intensive care. / KEY FINDINGS: Several routes of clonidine administration have been investigated for numerous indications in children, including perioperative sedation and analgesia. These include oral liquids, tablets, oral transmucosal systems, nasal sprays and rectal suspensions. Conflicting studies on oral transmucosal clonidine formulations suggest that further research is required to fully establish efficacy. Nasal sprays and rectal suspensions have the advantages of rapid onset of action and potential for dose flexibility, but predictable absorption is difficult to obtain. CONCLUSIONS: Provided age-appropriate strengths are available, IV formulations remain the most predictable in terms of bioavailability and flexible in terms of dose adjustment. However, as with all routes, down-titration is difficult given the long half-life of clonidine. Oral transmucosal systems, nasal sprays and rectal suspensions have potential in a less acute setting, but significant clinical work is required to elucidate a full pharmacokinetic and pharmacodynamic profile

Canadian infants' nutrient intakes from complementary foods during the first year of life

<p>Abstract</p> <p>Background</p> <p>Complementary feeding is currently recommended after six months of age, when the nutrients in breast milk alone are no longer adequate to support growth. Few studies have examined macro- and micro-nutrient intakes from complementary foods (CF) only. Our purpose was to assess the sources and nutritional contribution of CF over the first year of life.</p> <p>Methods</p> <p>In July 2003, a cross-sectional survey was conducted on a nationally representative sample of mothers with infants aged three to 12 months. The survey was administered evenly across all regions of the country and included a four-day dietary record to assess infants' CF intakes in household (tablespoon) measures (breast milk and formula intakes excluded). Records from 2,663 infants were analyzed for nutrient and CF food intake according to 12 categories. Mean daily intakes for infants at each month of age from CF were pooled and compared to the Dietary Reference Intakes for the respective age range.</p> <p>Results</p> <p>At three months of age, 83% of infants were already consuming infant cereals. Fruits and vegetables were among the most common foods consumed by infants at all ages, while meats were least common at all ages except 12 months. Macro- and micro-nutrient intakes from CF generally increased with age. All mean nutrient intakes, except vitamin D and iron, met CF recommendations at seven to 12 months.</p> <p>Conclusions</p> <p>Complementary foods were introduced earlier than recommended. Although mean nutrient intakes from CF at six to 12 months appear to be adequate among Canadian infants, further attention to iron and vitamin D intakes and sources may be warranted.</p