Richard Wilker Korsmeyer

Asymmetric-membrane tablet coatings for osmotic drug delivery

Abstract A new type of membrane coating has been developed for osmotic drug delivery that offers significant advantages over the membrane coatings used in conventional osmotic tablets. These new coatings have an asymmetric structure, similar to asymmetric membranes made for reverse osmosis or ultrafiltration, in that the coating consists of a porous substrate with a thin outer skin. These asymmetric-membrane coatings can be used to make osmotic drug-delivery formulations with several unique characteristics. High water fluxes can be achieved, facilitating osmotic delivery of drugs with low solubilities and making higher release rates possible. The permeability of the coating to water can be adjusted by controlling the membrane structure, thereby allowing control of the release kinetics without altering the coating material or significantly varying the coating thickness. In addition, the porosity of the skin can be controlled, minimizing the time lag before drug delivery begins and allowing the drug to be released from a large number of delivery ports. The use of asymmetric-membrane coatings on pharmaceutical tablets is described in this paper; the coatings have also been applied to capsules and multi-particulate formulations.

Critical questions in development of targeted nanoparticle therapeutics

One of the fourteen Grand Challenges for Engineering articulated by the US National Academy of Engineering is ‘Engineer Better Medicines’. Although there are many ways that better medicines could be engineered, one of the most promising ideas is to improve our ability to deliver the therapeutic molecule more precisely to the desired target. Most conventional drug delivery methods (oral absorption, intravenous infusion etc.) result in systemic exposure to the therapeutic molecule, which places severe constraints on the types of molecules that can be used. A molecule administered by systemic delivery must be effective at low concentrations in the target tissue, yet safe everywhere else in the body. If drug carriers could be developed to deliver therapeutic molecules selectively to the desired target, it should be possible to greatly improve safety and efficacy of therapy. Nanoparticles (and related nanostructures, such as liposomes, nanoemulsions, micelles and dendrimers) are an attractive drug carrier concept because they can be made from a variety of materials engineered to have properties that allow loading and precise delivery of bound therapeutic molecules. The field of targeted nanoparticles has been extraordinarily active in the academic realm, with thousands of articles published over the last few years. Many of these publications seem to demonstrate very promising results in in vitro studies and even in animal models. In addition, a handful of human clinical trials are in progress. Yet, the biopharmaceutical industry has been relatively slow to make major investments in targeted nanoparticle development programs, despite a clear desire to introduce innovative new therapies to the market. What is the reason for such caution? Some degree of caution is no doubt due to the use of novel materials and the unproven nature of targeted nanoparticle technology, but many other unproven technologies have generated intense interest at various times. We believe that the major barrier to the exploration of nanoparticles is because they are so complex. The very design flexibility that makes the nanoparticle approach attractive also makes it challenging. Fortunately, continuing progress in experimental tools has greatly improved the ability to study biology and potential interventions at a nanoscale. Thus, it is increasingly possible to answer detailed questions about how nanoparticles can and should work. However, a detailed understanding at the mechanistic level is only the beginning. Any new medicine must not only work at the molecular level, but must also be manufactured reproducibly at scale and proven in the clinic. New materials will require new methods at all scales. The purpose of this short article is to focus on a set of questions that are being asked in the large biopharmaceutical companies and that must be answered if targeted nanoparticles are to become the medicines of the 21st century.