Paroxetine hydrochloride

The utilization of IR spectroscopy is very important in the characterization of pseudopolymorphic systems, especially hydrates. It has been used to study the pseudopolymorphic systems SQ-33600 [36], mefloquine hydrochloride [37], ranitidine HC1 [38], carbovir [39], and paroxetine hydrochloride [40]. In the case of SQ-33600 [36], humidity-dependent changes in the crystal properties of the disodium salt of this new HMG-CoA reductase inhibitor were characterized by a combination of physical analytical techniques. Three crystalline solid hydrates were identified, each having a definite stability over a range of humidity. Diffuse reflectance IR spectra were acquired on SQ-33600 material exposed to different relative humidity (RH) conditions. A sharp absorption band at 3640 cm-1 was indicative of the OH stretching mode associated with either strongly bound or crystalline water (Fig. 5A). The sharpness of the band is evidence of a bound species even at the lowest levels of moisture content. The bound nature of this water contained in low-moisture samples was confirmed by variable-temperature (VT) diffuse reflectance studies. As shown in Fig. 5B, the 3640 cm-1 peak progressively decreased in intensity upon thermal... 

Paxil (Paroxetine Hydrochloride) Drug Substance, Formulation, Method of use Drug Substance, Formulation, Method of Use 5 Beginning 17 months into the first stay 65 months Over l bilhon... 

The FDA approved Paxil in December 1992. Patent No. 4,007,196 (the 196 patent) covering the active ingredient paroxetine hydrochloride had expired prior to this date and, therefore, was not listed in the Orange Book. However, GSK listed Patent No. 4,721,723 (the 723 patent) whieh elaims paroxetine hydrochloride hemihydrate. (A hemihydrate is a form of the active ingredient that has one water molecule for every two paroxetine molecules incorporated into its crystalline structure.)... 

The second and third patents on which GSK sued Apotex were anhydrate patents. The second was Patent No. 5,872,132 (the 132 patent), which claims paroxetine hydrochloride anhydrate (having no associated water molecules) and so differs from the hemihydrate form sold by GSK. In fact, the hemihydrate form is prior art to this patent and, thus, GSK represented to the Patent Office that the anhydrate is patentably distinct from the hemihydrate. GSK also sued on Patent No. 6,080,759 (the 759 patent), which claims the anhydrate made according to a specified process. The 132 and 759 patents raise the issue of whether polymorph patents should be listed in the Orange Book, discussed in Appendix H. 

An examination of two listed product-by-process patents illustrates this latter point. Patent Nos. 6,063,927 (the 927 patent) and 6,172,233 ( 233) both claim paroxetine hydrochloride made according to specified processes. In each case, the patent itself acknowledges that paroxetine hydrochloride was well known at the time the brand-name company applied for the patents. The brand-name company represented to the Patent Office in the patent document that the recited process was new and made the claims patentable. Therefore, if valid, these patents cover only those products (paroxetine hydrochloride) made according to the specified process, just as process patents cover products made according to the specified process. In contrast, product patents, such as listable drug substance and formulation patents, cover a product regardless of the process by which it is made. Thus, product-by-... 

C.F.R. 314.53(b). Examples of product-by-process patents are the three patents listed for Paxil (paroxetine hydrochloride). 

Paroxetine hydrochloride is a selective serotonin reuptake inhibitor that is used as an antidepressant. The chemoenzymatic synthesis can be carried out... 

Selective serotonin reuptake inhibitors fluoxetine hydrochloride fluvoxamine maleate paroxetine hydrochloride sertraline hydrochloride... 

Selective serotonin reuptake inhibitors paroxetine hydrochloride sertraline... 

USAN Paroxetine Hydrochloride Trade Name Paxil GlaxoSmithKline Approval 1992 M.W. 327.39... 

The most widely known SSRIs are fluoxetine hydrochloride (4, Prozac , Lilly), sertraline hydrochloride (5, Zoloft , Pfizer) and paroxetine hydrochloride (6, Paxil , GSK). Fluoxetine (4, Prozac ) was the first SSRl approved and effected a revolutionary change in the treatment of depression. In 2000, it was the most widely prescribed antidepressant drug in the United States with worldwide sales of 2.58B. Sertraline (5, Zoloft ) has been available in the United States since 1992 and had worldwide sales of 2.14B in 2000. Compared to fluoxetine (4), it has a shorter duration of action and fewer CNS activating side-effects such as nervousness and anxiety. Paroxetine (6, Paxil ) generated worldwide sales of 2.35B in 2000 and has a relatively benign side-effect profile, which favors its use with elderly patients. 

Synthesis of fluoxetine hydrochloride 10.3 Synthesis of sertraline hydrochloride 10.4 Synthesis of paroxetine hydrochloride 10.5 References... 

Paxil , 40 mg (paroxetine hydrochloride). Front (top) and back views. 

GlaxoSmithKline. (2007, August). Paxil CR (paroxetine hydrochloride) controlled-release tablets. Prescribing Information. Retrieved from www.GSK.com... 

---