Oral Modified-Release Delivery Systems

The oral route of drug delivery is typically considered the preferred and most patient-convenient means of drug administration. Consequently, much effort is directed during drug discovery to identify orally active candidates that will provide reproducible and effective plasma concentrations in vivo. The reality is that many compounds are either incompletely or ineffectively absorbed after oral administration (i.e., bioavailability is an issue), or that the required dosing frequency is too short to enable once- or twice-daily administration (i.e., pharmacokinetic half-life is an issue). Lead optimization typically addresses such shortcomings
during a discovery program; however, in many cases it is not possible to identify an appropriate clinical candidate with the requisite “ideal” physicochemical and/or pharmacokinetic properties. For clinical research phase drug candidates, or drugs already marketed, the opportunity for enhancing their clinical pharmacology profile after oral administration through attainment of more optimal blood drug concentration-time profiles should always be considered.

Modified-release formulation technologies offer an effective means to optimize the bioavailability and resulting blood concentration-time profiles of drugs that otherwise suffer from such limitations. Within the context of this chapter, the term “modified release” refers to both delayed- and extended-release systems for oral administration as well as oral delivery systems designed specifically to modify the release of poorly water-soluble drugs. Also included are the fastdissolving dosage forms for which absorption occurs primarily (but not exclu-sively) in the gastrointestinal (GI) tract. The chapters in this part describe a broad range of pharmaceutical formulation technologies that address various limiting features associated with oral drug bioavailability and dosing frequency. In planning this part, we invited technology-focused chapters from expert contributors who had direct experience with the individual systems. Our goal was to select relatively advanced technologies representative of the various contemporary approaches being taken in the field—our success in this endeavor is a direct consequence of the willingness of the contributing authors who graciously accepted our invitation. As with all written compilations of this nature, time, commercial, and intellectual property restrictions on the part of potential contributors unfortunately precluded the description of some highly relevant and successful technologies.