JEFFREY PETER PEARSON
Professor of Molecular Physiology Newcastle University U.K.
and Chief Scientific Officer of Aelius Biotech Ltd.

Abstract

Oral delivery would be the favoured route of drug administration (1). Other routes include intranasal, allowing fast delivery to the brain, pulmonary using aerosolised compounds, transdermal, buccal and intravenous or transdermal AI controlled closed loop infusion pumps (2). To enhance delivery, drug formulations can be enclosed in lipid e.g. liposomes or encapsulated to protect and direct delivery or treated to increase solubility e.g. spray drying (3). In the oral route attempts may be made to protect the stomach from damaging effects such as those of NSAIDs (4). In terms of oral delivery for a compound to be absorbed it must overcome three major barriers, the digestive barrier, the mucus barrier and the epithelial barrier in sufficient amounts to yield a therapeutic effect. The mucus barrier is also relevant in intranasal and pulmonary delivery. Current models to test absorption now include an in vitro gut model including the 3 barriers combined with absorption (5). In addition this article will also discuss examples where natural products could replace chemically synthesised drugs. The pharmaceutical industry increasingly relies on outsourcing to CROs for research and drug delivery development activities. What are seen as challenges by the pharmaceutical industry have become opportunities for CROs (6).

Why is oral delivery the desired route for delivery of most drugs? It is due to enhanced patient compliance, lower cost and less side effects. However several problems must be overcome including solubility, low solubility then low bioavailability.

Digestion: e.g. peptide based drugs could be digested by the proteolytic enzymes in the stomach and the small intestine. Absorption: overall charge is important for absorption and the drug must pass easily through the SI mucus layer. The stomach is not an absorptive organ and may need to be protected from damage by the drug. Lipid formulations consisting of oils/triglycerides and surfactants can increase solubility of lipid soluble drugs, which can be dispersed as emulsions (self emulsifying drug delivery systems, SEDDS) in the aqueous environment of the GI tract (7). A downside is that the lipids can be digested in the intestine via pancreatic lipases which could lead to release of some of the active with reduced solubility. However if surfactants are present this can result in the creation of micelles, which can be absorbed as mixed micelles formed into chylomicrons in the enterocytes and enter the lymphatic system an ...