Drug delivery via the rectum is a useful alternative route of administration to the oral route for patients who cannot swallow. Traditional rectal dosage forms have been historically used for localized treatments including delivery of laxatives, treatment of hemorrhoids and for delivery of antipyretics. However, the recent trend is showing an increase in the development of novel rectal delivery systems to deliver drug directly into the systemic circulation by taking advantage of porto-systemic shunting. The present review is based on research studies carried out between years 1969–2017. Data for this review have been derived from keyword searches using Scopus and Medline databases. Novel rectal drug delivery systems including hollow-type suppositories, thermo-responsive and muco-adhesive liquid suppositories, and nanoparticulate systems incorporated into an appropriate vehicle have offered more control over delivery of drug molecules for local or systemic actions. In addition, various methods for in vitro–in vivo evaluation of rectal drug delivery systems are covered which is as important as the formulation, and must be carried out using appropriate methodology. Continuous research and development in this field of drug delivery may unleash the hidden potential of the rectal drug delivery systems.

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.

Introduction Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. Methods and analysis The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2–18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Ethics Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial Registration EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results.