Targeting PK And Patient Needs With Versatile, Timed-Based Oral Drug Delivery

By Michael A. Gosselin, Ph.D., and Vincent Parrino, M.Sc., M.B.A., Aptalis Pharmaceutical Technologies

In 2009 more than one-half of the drug candidates going beyond Phase 2 development were line extensions or modifications of existing products, rather than representing truly innovative new molecules, according to a 2010 annual report from the consultancy firm CMR International, a Thomson Reuters business [1]. Clearly, pharmaceutical developers pursue product opportunities that meet patients’ needs not only by discovering new molecular entities (NMEs), but largely by repositioning existing products across multiple indications, developing alternative dosage forms, or reformulating them to modify pharmacokinetic profiles. Drug delivery technologies enable a significant number of these market strategies. In particular, the industry has successfully leveraged oral modified-release products in multiple therapeutic areas. Some were developed internally and others were developed with an external technology partner. A few well-known commercial examples that were recently launched are highlighted in Table 1. Pharmaceutical developers are incorporating drug delivery technologies in the earlier stages of product development in order to create differentiated products, whether they are drugs not yet approved in the U.S. or reformulations of existing drugs. Features such as delayed/timedspecific release and sustained therapeutic coverage are becoming a prerequisite for new formulations of oral medications in order to achieve significant market share in many therapeutic areas. Examples include treatments for overactive bladder, ADHD, GERD, schizophrenia, and anti-viral therapy because such formulations, and their resulting pharmacokinetic profiles, target specific underserved patient needs. To meet these commercial expectations with an oral, modified-release dosage form, developers face multiple challenges during formulation development. Examples include poor drug stability, low aqueous or pH-dependent solubility, narrow therapeutic windows, and food effects, among others. One particular formulation challenge is optimizing timed-based pulsatile and sustained delivery profiles using multi-layered particulate dosage forms, for both acidic and alkaline drugs.