Sertraline HCl is the active ingredient in Zoloft®, the world’s best selling treatment for depression, with 2002 sales in excess of $2 billion. It also happens to be a rather highly polymorphic compound. Pfizer clearly began to see this during development of the compound when it identified and patented 4 additional solid forms, one of which turned out to be the most stable polymorph. Competitors have since identified and claimed 13 additional solid forms of sertraline HCl, bringing the purported total number of solid forms to 18. Against this backdrop, consisting of several years of form discovery studies on sertraline HCl by multiple companies, TransForm decided to run the same compound through CrystalMax®, to test our ability to be comprehensive. Within 3 months, TransForm scientists had conducted > 6,200 crystallization experiments and identified a total of 36 forms of sertraline, including:
| 8 polymorphs, 7 solvates and several hydrates of the HCl salt, including all known non-transient forms | |
| 2 previously unreported solid forms of the HCl salt, one of which is pharmaceutically acceptable | |
| 16 novel salt forms of sertraline, at least three of which appear to be considerably less polymorphic than the HCl salt. |
While the patent on the new chemical entity (NCE) runs out at the end of 2005, a further patent on Pfizer’s preferred (and most stable) crystalline form does not expire until early 2012. Notwithstanding the presence of this patent, Pfizer does not appear to have successfully protected its Zoloft® franchise beyond expiration of its NCE patent. In part, this is because Pfizer faced tough and creative generic competitors and maybe because several others, not Pfizer, filed patents on a large number of alternative forms of Pfizer’s compound, beginning as early as 8 years before the expiry of the NCE patent.