C&EN, November 12, 2018
Hovione for CPhI 2003
The service of an API manufacturer not only involves the development of the chemical process and the supply of high quality API, when and where required, but also paying close attention to those physical parameters which make up the necessary requisites for a successful formulation. Chemical skills must be complemented by a pharmaceutical culture. For a successful custom synthesis partnership it is imperative that the API contractor be both cognizant of the importance of having the correct particle size and morphology, and be able to develop a process that delivers consistently the required crystal form and size. This is key in many galenic forms; in the field of inhalation for instance it is absolutely critical; it can also be the source of many last-minute surprises and frustrations until the matter is well controlled.
Traditional know-how includes: expertise in controlled crystallisation, micronization and jet milling. These are skills that Hovione has used for decades in its plants to achieve the desired crystal form and consistent particle size. All of this needs to be backed up with analytical techniques, including laser diffractometry and impaction, used in a manufacturing scenario, to assure the necessary QC controls.
But technology moves on….
Hovione is pleased to announce it is installing a state of the art Spray Drying facility, capable of evaporating 35 to 90 Kg of water per hour under the most stringent cGMP conditions. The supplier of the Spray Drier, Niro A/S has designed this to the most advanced specifications. It is equipped with two atomizer systems (a rotary and co-current two-fluid nozzle) to deliver injectable grade APIs and is configured to be “cleaned-in-place” it discharges into a classified clean-room. This multipurpose unit was the result of a close collaboration with Niro and allows Hovione to produce dry solids in either powder, granulate or agglomerate form from liquid feedstocks such as solutions, emulsions and pumpable suspensions. This technology will enable continuous production, at low-cost and with a high degree of precision, over a wide range of particle sizes. The system meets explosion-proof requirements and can therefore spray-dry out of most organic solvents in a safe and compliant environment. Niro has described the unit as one of the most flexible and versatile GMP compliant spray-driers that they have ever built.
Continuing its programme to expand scientific know-how in advanced technologies, Hovione is actively developing expertise in other particle design techniques: Supercritical Crystallization and Sono-crystallization.
Supercritical crystallization offers a trouble-free separation of the product from the solvent and the capability to control the size and form of the crystals. The principle is based on replacing a conventional solvent with a supercritical fluid, which may act as a solvent or as an anti-solvent. This technique may be used to produce very small particles with narrow size distribution.
Sono-crystallization uses ultrasound to influence crystallization behaviour by promoting cavitations within the liquid media, which serve as nuclei for new crystals to form. Benefits can include improved crystal habit, purity and the ability to manipulate crystal-size distribution and powder flow characteristics. It also offers a useful and more controllable alternative to seeding.