It is now 10 years (almost exactly) since the US launch of GSK’s blockbuster combination asthma medication Advair and over 12 years since the launch of Seretide equivalent in Europe. Advair currently has a “black box” warning, which a precautionary statement given to the drug by the FDA. This warning has come about as a result of various studies on the safety of salmeterol (the bronchodilator in the product – the “partner” steroid being fluticasone) that revealed a small increase in the risk of death and hospitalization when taking salmeterol. So what does the future hold for the current drug? My view is that design and production of engineered particles containing both drugs will assist in the efficacy of the combination product by ensuring delivery of both drugs in the exact amounts to all areas of the lung, and maybe then the patient can use less of one or both of the active drugs particularly if the synergy argument can be proven. Then will the “black box” warning still apply?

Often I am asked for the common methods of API crystal habit modification to improve API flow properties in pharmaceutical industry. Screening solvents? Use of additives? Computational and predictive techniques? Well, having been involved with this type of activity for a number of years one useful avenue of exploitation is by using prolific nucleation via the application of power ultrasound - sonocrystallization. By doing so you stand a chance of achieving nucleation at low supersaturation (SS) at the expense of crystal growth and this should give you a useful handle on modifying growth rates of different faces of the crystal – for example instead of preparing long needles at modest to high SS you can often back off the SS to achieve some useful width on the crystals and the expense of rapid elongation. Often you can work just within the equilibrium solubility boundary where both nucleation and growth kinetics are often very slow. The consequences are you can obtain rods rather than needles that have better flow characteristics, less included impurities, less kinetic roughening and altogether a much better product. As a further bonus by working at lower supersaturation you stand more of a chance of obtaining thermodynamically stable (and maybe new) polymorphs. For dramatic morphology change (such as obtaining spheroidal crystals) other sonocrystallization techniques involving initial spray drying can be useful. Prosonix UMAX (Ultrasound mediated amorphous to crystalline transition) is one such method. Of course you need pure material to start with but the final product can be very interesting whether for oral or respiratory use. If you have specific problems or would like to evaluate useful equipment / techniques for sonocrystallization please let me know