A real life exemple
 Polymorphism
 Technological aspects
 Expert appraisal
 An expanding market

A real life exemple

xxxxx Laboratories have announced that deliveries of xxxxx capsules have been suspended. xxxxx capsules contain xxxxx active substance, an inhibitor of HIV protease, and have shown inadequate dissolution characteristics. The appearance of a new crystalline form of xxxxx has meant that certain production batches of xxxxx capsules do not meet the specifications of the dissolution test. This could affect drug bioavailability. xxxxx stated that no solution to this problem has yet been found... For the time being, the company cannot predict the financial consequences of halting xxxxx production, for which sales were expected to reach 250 million dollars in 1998.

Polymorphism

Polymorphism is the capacity of an organic or mineral substance to take the form of at least two different crystalline structures, even though the chemical structure remains the same.

Flurbiprofen : Form II	Flurbiprofen : Form I

Technological aspects

In-depth knowledge of a drug's potential polymorphism and its pharmaceutical formulation is essential to optimize its therapeutic activity. Once this knowledge has been acquired the drug can be controlled for its :

• Crystal habit
• Stability (exposure to mechanical strain, humidity, radiation and heat)
• Solubility
• Dissolution rate
• Bioavailability
• Toxicity

The active substance may undergo modifications in its crystalline structure during production, storage or use. Modifications can be predicted and thus may be reduced by the controls listed above. Marketing errors with new drugs can therefore be avoided. The consequences of such errors are often dramatic from a financial as well as a commercial point of view. (e.g. exemple on the previous page).

Expert appraisal

Drug polymorphism and the interactions between different components (active substance and excipients) have been studied in the "Laboratoire de Chimie Minérale et Générale" at the Faculty of Pharmacy in Montpellier since the 1970s. CaLytherM's founders, Fabienne LACOULONCHE and Alain CHAUVET, worked in this laboratory in collaboration with Professor MASSE, the driving force behind these methods.

An expanding market

To secure FDA (Food and drug Administration) and EMEA approval it is critical for the pharmaceutical industry to select the optimum solid form for manufacture.

Do you face potential problems with polymorphism during research and development of new drugs ? Contact us now !