Coating processes represent one area where the FDA has expressed concern because they involve so many factors that can influence the outcome. A major challenge going forward is to control coating processes more effectively, which can only be done by gaining a full understanding of the key issues taking place in any given coating process. To gain a better understanding of what is a very dynamic process, pharmaceutical companies, in conjunction with academia, are using various modeling techniques, such as computational fluid dynamics (CFD) and discrete element methods (DEM). Additionally, application of thermodynamic principles provides a greater opportunity to understand how best to balance spray application with the drying process.

In keeping with the principles of the QbD initiative, employing statistical design of experiments (DoE) provides an effective means of identifying all critical formulation and process variables essential to designing a quality pharmaceutical dosage form. DoE provides the greatest opportunity for examining the critical interactions between ingredients within a formulation and process variables for effective optimization of pharmaceutical formulations (including coating formulations) and processes.

With respect to coated products, the full implementation of QbD and on-product anti-counterfeiting initiatives for coated products are two issues likely to demand even closer attention in the future.

The Future of Drug-Solubility Technology

Greater sophistication in drug discovery is leading to the identification of a growing number of molecules that are proving more potent for disease control. Many of these compounds, however, are also proving very poorly water soluble and in some cases poorly permeable. Indeed, nearly 40% of the drugs on the market today and nearly 60% of drugs in development are poorly soluble. So solubility will be a major challenge for pharmaceutical scientists in the years to come, a situation that could be compounded by the discovery of more and more poorly soluble molecules.

Conventional tablet-forming techniques are not proving adequate to the challenge, and other technologies will gain prominence in the coming years. These may include hot-melt extrusion, nanocrystal technology, and spray-dried solid dispersions technology. Spray-dried solid dispersions technology enables the formation of an amorphous state that is clearly at a high energy level and, for this reason, able to dissolve into the dissolution medium much more effectively than if it were in a highly structured, crystalline form. Amorphous dispersions will enable drugs to be administered in more controlled dosages at lower concentration levels, thus providing the same level of therapeutic benefit with reduced risk of any potential side effects that may be associated with that drug.

However, one challenge that will need to be addressed is the stability of amorphous dispersions over time. The potential exists that new polymers or polymer systems may be needed to help stabilize amorphous solid dispersions. Pharmaceutical scientists will have to work on enabling these materials to have a shelf life of at least three to five years.

Depending on the molecule, one solubility technology may work better than another. One thing is certain: conventional micronizing technology will not be nearly as effective as the newer technologies. For example, spray-dried dispersions have been demonstrated to achieve 10- to 50-fold increases in bioavailability over conventional dosage forms.

To this point, some products of increased solubility have been commercialized using hot-melt extrusion technologies and nanocrystals. With the question still looming as to whether it is possible to make stable amorphous dispersions, spray-dry technology stands on the threshold of the marketplace. The next decade promises to be very promising in the delivery of stable amorphous spray-dried drug products.

Albert W. Brzeczko, PhD, vice-president of global pharmaceutical research and development and pharmaceutical technologies, ISP Pharma Systems LLC

Industry experts give their predictions for the next 30 years. Read Editor-in-Chief Michelle Hoffman's introduction here. See what's next in:

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