4.1. Rationale and Approaches

In the book "Controlled Drug Delivery" the authors define the rational for sustained or controlled drug delivery as 'to alter the pharmaco-kinetics and pharmacodynamics of pharmacologically active moieties by using novel drug delivery systems or by modifying the molecular structure and/or physiological parameters inherent in a selected route of administration.'. In other words, the kinetics of drug uptake and the maintenance of plasma drug concentration is determined not by the properties of the drug, but by the properties of the delivery system. This affords a level of control over the concentrations of drug in the body, that is not available in conventional methods, with the exception of metered intravenous administration.

As we saw in chapter three, the traditional methods and routes of drug administration result in a rate of drug uptake that is controlled by the drug properties (solubility, charge, molecular size, etc.) and the characteristics of the site of administration (pH, surface area, presence of enzymes, active transport mechanisms etc.). The profiles of drug levels in the plasma are also influenced by the rate of the various elimination processes. Figure 4.1.1 shows the plasma drug profile for drug administered by repeated oral doses (traditional) and compares it with the profile from a sustained release device and one delivering drug by zero order kinetics. The traditional method results in peaks and valleys, which are absent in the controlled and sustained formulations.

Figure 4.1.1. Concentration profiles for drug delivered by tablet, sustained release device or controlled release device

The type of delivery vehicle that is chosen for investigation will depend on many factors, including the properties of the drug, its pharmacodynamics and pharmacokinetics, the route of delivery and the nature of the treatment and the disease. Delivery of Insulin is a challenge because it is only required when blood glucose levels exceed normal levels, and so a responsive drug delivery device would be optimal. However, as we have discussed, Insulin is a large molecular weight drug, a protein that needs to maintain its active configuration, and one that is susceptible to the protease enzymes in the body, resulting in a half life of about 25 minutes.