The future of oral controlled release

In-PharmaTechnologist.com caught up with Vishal Gupta, director of pharmaceutical R&D at Covidien (formerly Tyco Healthcare), to talk about what the future holds for oral controlled release formulations. Emerging technologies have given a new lease of life to oral drug formulations, with controlled release platforms opening new windows for pharma firms looking to extend a product's life and offer more convenient treatment options to patients. Johnson & Johnson's Concerta (methylphenidate) and Shire's Adderall (amphetamine-dextroamphetamine) are just two examples of drugs given the extended release treatment, both billion dollar franchises. With growing interest in the potential controlled release formulations could have for their products, pharmaceutical companies are increasingly investigating controlled release platforms and their suitability for drug products in their portfolios. "I think there's a mushrooming of more and more institutions making the foray into controlled release…it's a very crowded space,"​ Gupta told in-PharmaTechnologist.com at the recent Controlled Release Society meeting in California. "There are many reasons why the drug delivery field has spawned into such a huge business. Large pharmaceutical companies have a hard time coming up with new blockbuster candidates, and at the same time their old molecules are expiring. In the face of stiff generic competition, many of these brand companies are trying to come up with value-added controlled release systems of their older compounds." ​ In Gupta's view, there are three main areas in which attention is likely to be focused as the oral controlled release field develops. The first of these is development of new polymers and biopolymers, which will give companies much more control over the drug release profile of their drugs. "There are a few polymeric materials being used, but not very many,"​ said Gupta. ​"We are still limited by the materials that are available…the drugs that are coming out have very unique properties and sometimes you just need very customised, very tailored polymeric materials to achieve the required release profiles." ​ Another area where developers are likely to concentrate is in the spatial delivery of compounds in the body, according to Gupta. Although the temporal aspect of drug delivery will necessarily have been considered in depth in controlled release formulations, most drug products currently available are released into the entire bloodstream. So as well as reaching the target treatment site, the drug also goes to organs and tissues where it simply isn't needed. As such, research into more targeted techniques in controlled release drug delivery is likely to be a very active area of R&D in the field in Gupta's view. The third key area where research into oral controlled release techniques is likely to bloom is in the development of 'smart' drug delivery systems, already a hot topic in many R&D units. "The word 'smart' has different connotations, different people have different meanings for what constitutes 'smart' drug delivery systems,"​ commented Gupta, but in his view, developing smart systems essentially means "optimising drug therapy, coming up with intelligent release profiles - reproducible, customisable release profiles".​ Intellectual property (IP) is a key element of the drive for pharma firms to investigate the potential of controlled release formulations; coming up with a new formulation for a former immediate release product not only extends a company's IP estate, but can help defend against generics and maintain a company's market share. Shrewd timing of the introduction of a new controlled release form can mean companies benefit from a staged launch of different versions of the same drug, maximising revenues and extending product protection. For companies developing and offering controlled release technology platforms, the market is also clearly growing, with delivery platforms that offer tailored release profiles garnering increased attention from pharma firms. As for Gupta's firm Covidien (formerly the healthcare division of Tyco and recently relaunched in its own right), drug delivery is set to play a growing role in the company's activities, with the firm's R&D spend set to double over the next three years. The company has recently patented two new drug delivery technologies, which between them can offer just about any desired release profile, according to Gupta. The first technology makes use of hybrid polymer systems to generate a customised release profile, and the second technology combines the advantages of a matrix controlled release system with that of a reservoir system, both commonly used in controlled release formulations. By combining the two delivery systems, Covidien can develop drugs that remove the potential of dose dumping (a risk associated with the reservoir delivery system), and deliver a tailored, predictable release profile. Despite the advances being made by Covidien and other pharmaceutical firms, oral controlled release does have challenges lying before it. The controlled delivery of large molecules without denaturation and degradation of the compound is a particular test for controlled release, and although some firms have experienced success in this area, further research could help exploit the potential of controlled release further. Resolution of various biopharmaceutics issues, such as in vitro​ prediction of how food will affect bioavailabilty of a drug in vivo​, is another area where Gupta hopes there will be a more dedicated research effort. "It's an exciting time in drug delivery, and I think the field is going to see very many advances in the coming years,"​ said Gupta, and judging by the number of products in development across the industry hoping to offer more convenient and less frequent dosing regimes, controlled release products are likely to play an ever more prominent role on the pharmaceutical stage.