Novel mechanisms of drug delivery

A fundamental tenet of antiepileptic drug (AED) therapy is delivery of the right amount of drug at the right time to the site of action. Currently available AED delivery systems used for research or in clinical practice have shortcomings that can hinder laboratory studies or optimizing therapy in patients. This is due, in part, to the fact that most approved and investigational AEDs possess physicochemical and pharmacological properties that affect drug delivery. Among these properties are poor water solubility (e.g., carbamazepine, lamotrigine, oxcarbazepine, phenytoin, rufinamide); slow, incomplete, or irregular oral absorption (e.g., carbamazepine, phenytoin, rufinamide, valproic acid); influx or efflux transport in the gastrointestinal tract or the blood-brain barrier (e.g., gabapentin); and relatively short elimination half-lives necessitating two or more daily doses (e.g., carbamazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, valproic acid). Collectively, these properties complicate the design and interpretation of AED studies in animals and limit the effectiveness and safety therapy in patients due to problems with drug delivery or poor medication adherence. Advances in the pharmaceutical sciences over the last decade have resulted in innovative delivery systems directed at enhancing the effectiveness and safety of drug therapy. These systems are particularly relevant to AED therapy, given the drug delivery challenges this therapeutic class presents. The new delivery platforms can enhance bioavailability, control drug release, overcome transport interactions, enable targeted delivery, reduce dosing frequency, and permit the formulation of safer, more useful enteral and parenteral solutions of poorly soluble AEDs.This chapter reviews recent advances and developments that are being used, or could be used, to achieve greater control of AED delivery in laboratory studies and improve therapy in patients. The text is divided into different sections, each of which deals with a particular route for drug delivery. This chapter, however, does not consider the currently marketed AED formulations in detail, as there are several excellent reviews to which the reader is referred (Bialer, 2007; Fisher and Chen, 2006; Fisher and Ho, 2002; Pellock et al., 2004; Wheless and Venkataraman, 1999).