Novartis Ag

Tonix Pharma Holdings Limited

Abiogen Pharma S.p.a.

Eleison Pharmaceuticals, LLC

Targent, LLC

Stefano Luca Giaffreda

Serena Fabbroni

Michel Chiarucci

Mark G Bock

Piotr Henryk Karpinski

Dario Braga

Yves Auberson

Thomas Josef Troxler

Stephanie Kay Dodd

Xiaoyang Wang

Xuechun Zhang

Marco Curzi

Tie-Lin Wang

Mark T Edgar

Fabio Neggiani

Haiyang Jiang

Elena Dichiarante

Barbara Politi

Enrico Modena

Michael Roeder

Kesheng Zhang

Laura Dini

Alex Petrolati

Hayang Jiang

Tielin Wang

Mark Gary Bock

The present invention relates to a new process for the preparation of the crystalline polymorph of sodium neridronate in form hemihydrate F, comprising the following steps: a) reacting the 6-aminohexanoic acid with a mixture of phosphorous acid and methanesulfonic acid at a temperature in the range from 60 to 80&#xb0; C., under stirring, until a clear solution is obtained; b) adding phosphorus trichloride to said solution of step (a) under stirring at a temperature in the range of 60 to 80&#xb0; C.; c) diluting with water the reaction mixture obtained from the previous step (b) and heating said water diluted mixture at a temperature in the range from 80 to 120&#xb0; C.; d) cooling the heated mixture obtained in step (c) up to room temperature, diluting it with water, then slowly adding an aqueous sodium hydroxide solution up to a pH in the range from 4.2 to 4.6, to obtain a neutralized solution; e) bringing the neutralized solution of step (d) up to a temperature of about 70&#xb0; C., then subjecting it to a temperature increase in the range from 70 to 140&#xb0; C., until evaporation of at least 70% of the initial volume of the neutralized solution of step (d), thus obtaining a suspension to be kept under stirring for at least 1 hour; f) cooling the suspension of step (e) up to a temperature in the range from around 5 to 25&#xb0; C.; and g) recovering the crystalline sodium neridronate in hemihydrate form F by filtering the suspension of the previous step (f). The process is particularly simple, scalable and environmentally sustainable.

Process for the preparation of the polymorph F of sodium neridronate

Described herein are polymorphic forms of 1,6-dibromo-1,6-dideoxy-dulcitol (dibromo dulcitol or DBD), which is a known antitumor agent. Also described are methods of making these new crystalline polymorphic forms as well as methods of using these polymorphic forms to treat cancer.

Crystalline polymorphs of 1,6-dibromo-1,6-dideoxy-dulcitol

Disclosed herein is an oxalate salt/co-crystal (tianeptine oxalate) of (RS)-7-(3-chloro-6-methyl-6,11-dihydrodibenzo[c,f] [1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide (tianeptine) as shown in Formula I: 

Tianeptine oxalate salts and polymorphs

The present invention relates to a novel crystalline hemihydrate polymorph of neridronic acid sodium salt, and a novel process for the preparation thereof comprising the steps of: 1) dissolving solid sodium neridronate in any crystalline form in water, at a temperature in the range from 70 to 90&#xb0; C., to obtain an aqueous solution of sodium neridronate; 2) adding a solvent selected from the group consisting in ethanol, 1-propanol, and 2-propanol to the aqueous solution obtained from step (1), so that the final water:solvent volume ratio is in the range from 1:0.5 to 1:1, thus obtaining a suspension; 3) placing the suspension obtained from step (2) under mechanical stirring, at a temperature in the range from 60 to 95&#xb0; C.; 4) recovering the crystalline hemihydrate form F of sodium neridronate formed in the previous step (3). The crystalline hemihydrate form F of sodium neridronate, particularly stable, may be employed in the preparation of solid oral pharmaceutical forms for use in the treatment of musculoskeletal and calcium metabolism disorders.

Polymorph of sodium neridronate and preparation process thereof

The invention relates to compound of the formula I or a salt thereof, wherein the substituents are as defined in the specification; to its preparation, to its use as medicament and to medicaments comprising it.

Carbamate/urea derivatives

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Bologna, Italy

Stefano Luca Giaffreda