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European Pharmaceutical Contractor
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| Can oral controlled drug delivery meet the challenges posed by chronotherapeutics? Clive Wilson of the Department of Pharmaceutical Sciences, Strathclyde Institute for Biomedical Sciences and Neena Washington, a Consultant Senior Scientist, investigate the impact of our ticking body clocks and how to get the most out of drug therapies
Traditionally, it has been taught that the homeostatic mechanisms of the body hold systems in equilibrium with little deviation, whilst allowing fluctuations to accommodate the body’s changing demands and requirements. However, chronobiology has long recognised that biological systems alter by day or season, taking their cue from the environment – mating seasons for animals and flowering seasons for plants for instance – and that a ‘body clock’ alters the overall homeostatic controls of the body.
The magnitude by which a ‘body clock’ affects almost all systems is still quite a new concept and has been shown to affect periodicity and/or amplitude. The best known of these is the circadian rhythm, which approximates to one day and includes a growth hormone, which peaks during sleep, and levels of plasma testosterone and cortisol, which typically peak in the early morning. There are other rhythms such as the ultradian, which are shorter than a day (for example, the milliseconds it takes for a neuron to fire or a 90-minute sleep cycle) and the infradian, referring to cycles longer than 24 hours (for example, monthly menstruation).
What is less well recognised is that the disease state of a body will also display a periodicity (1). The realisation that this occurs has led to the development of chronotherapeutics – a new branch of therapy – which aims to take maximum advantage of the disease’s chronobiology in order to provide optimum plasma levels of drug, resulting in maximum health benefit and minimum side effects for the patient. This can be achieved by accurately timing both the dosing of the patient and the release of the drug from the delivery system. This new science is questioning the traditional prescription of medication at evenly spaced time intervals throughout the day. This is an attempt to maintain constant levels throughout a 24-hour period, as more evidence is obtained to link improved efficacy with administration co-ordinated with day-night patterns and biological rhythms (2). |
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Professor Clive G Wilson holds the JP Todd Chair of Pharmaceutics at Strathclyde University in Scotland, although currently he is on a sabbatical research period. His work has focused on the use of imaging techniques in formulation research, and he has received the Amersham and Pfizer awards in recognition of his contribution to this field. His main areas of research are the relationship between gastrointestinal physiology and drug absorption, and the problems of ocular drug delivery. He has supervised more than 40 PhD students and has authored over 400 publications, including original articles, reviews and six books. The publications reflect his interest in imaging, physics, drug absorption and metabolism, and pharmacokinetics. He is a member of the editorial board of the European Journal of Pharmaceutics and Biopharmaceuticsand Editor of the Taylor & Francis series in pharmaceutical technology.
Dr Neena Washington has worked extensively both in academia and the pharmaceutical industry. She earned her BSc (Sp Hons) in Physiology and Pharmacology from Sheffield University, prior to earning her PhD in Pharmaceutics at Nottingham University. As a Consultant Senior Scientist, her main areas of interest are the in vivobehaviour of dosage forms and the use of imaging techniques, particularly gamma scintigraphy, in the visualisation of dosage form behaviour in man. Her clinical interests are in the fields of gastrointestinal, respiratory, inflammation and oncology. |
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Dr Neena Washington |
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