A crystalline form of sertraline hydrochloride was found, referred to hereinafter as polymorphic form CSC2 having a dissolution rate which surprisingly will increase rate of absorption of a drug. Furthermore, different crystalline forms of sertraline hydrochloride alcohol solvates, crystalline forms of sertraline hydrochloride hydrates, referred to hereinafter as polymorphic form CSC1, a process for the preparation of the amorphous form of sertraline hydrochloride, and different processes for the preparation of polymorphic forms I, II, V, and T1 are disclosed.

Polymorphic forms of sertraline hydrochloride

The present invention is directed to novel polymorphic Forms XI, XII, XIII, XIV, XV and XVI of sertraline hydrochloride, to processes for preparing them, methods of using them to treat disease, methods of using them to make other sertraline hydrochloride forms, and to pharmaceutical dosages containing the novel forms.

Novel sertraline hydrochloride polymorphs, processes for preparing them, compositions containing them and methods of using them

The present invention is directed to Form II of sertraline hydrochloride and novel methods for its preparation. According to the present invention, sertraline hydrochloride Form II may be produced directly form sertraline base or sertraline mandelate. It may also be produced from sertraline hydrochloride solvate and hydrate forms, and crystallized from new solvent systems. Pharmaceutical compositions containing sertraline hydrochloride Form II and methods of treatment using such pharmaceutical compositions are also disclosed.

Sertraline hydrochloride Form II and methods for the preparation thereof

An internal teeth oscillating inner gearing planetary gear system is provided with an input shaft, an eccentric gear rotated by the input shaft, the internal oscillating body oscillatingly rotated through the inner circumferential surface of the eccentric gear, and an external gear meshed with the internal oscillating body.

Internal teeth oscillating inner gearing planetary gear system

Provided are processes for preparation of crystalline sertraline hydrochloride Form II substantilly free of other polymorphic forms of sertraline hydrochloride, preferably on an industrial scale.

Processes for preparation of polymorphic form II of sertraline hydrochloride

PROBLEM TO BE SOLVED: To provide hollow reduction gear that can accommodate, in a hollow portion thereof, piping for leading a large diameter transmission shaft of another system, fluid including air and water, an electric wire, and the like, without an increase in size and weight and without a sleeve or a guide. SOLUTION: The hollow reduction gear has output shafts 1 and 2 having the hollow portion 23 and having a plurality of external gears of a semicircular arc groove shape positioned evenly on an outer circumference, and cases 5 and 6 rotatably supported on the output shaft outer circumference via a pair of main bearings 7 for supporting an external load, and has, outside the output shafts, eccentric internal gears 4 having internal teeth of a semicircular arc groove shape so that rotation of eccentric crank portions 12a and 12b formed on a plurality of crankshafts 12 arranged parallel to an axis (a) causes the eccentric internal gears to revolve axes b of the crankshafts around the axis (a) as eccentrically moving along the plurality of external gears with which they can engage.

Hollow reduction gear

PROBLEM TO BE SOLVED: To obtain a sertraline hydrochloride having excellent solubility in various solvents and bioavailability and a crystal structure of metastable form by dissolving a sertraline free base in a solvent or suspending a sertraline organic acid salt in a solvent and introducing hydrochloric acid or hydrogen chloride to the solution or suspension. SOLUTION: A sertraline free base is dissolved in a solvent (e.g. an ester- based organic solvent such as ethyl acetate, butyl acetate or the like or a ketone-based organic solvent such as acetone, methyl isobutyl ketone or the like) or a sertraline organic acid salt is suspended in a solvent, and hydrochloric acid or hydrogen chloride is introduced into the solution or suspension preferably at a room temperature or the reflux temperature of the solvent to give sertraline hydrochloride crystal of metastable form of the formula. The sertraline free base is obtained, for example, by a method for decomposing sertraline mandelate with an alkali. The amount of the hydrochloric acid or hydrogen chloride used is preferably 1.0-5.0 mol based on 1.0 mol of the sertraline free base or the organic salt.

Production of sertraline hydrochloride

PROBLEM TO BE SOLVED: To obtain sertraline hydrochloride crystal useful as an antidepressant and to provide a method for industrially producing sertraline hydrochloride crystal SOLUTION: (1S,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1- naphthylamine hydrochloride methanolated substance has diffraction peaks based on its crystal structure in a powder X-ray diffraction diagram when angles 2θ are at least 123 deg, 178 deg, 220 deg, 234 deg and 248 deg (1S,4S)-4-(3,4- Dichlorophenyl-)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride ethanolated substance has diffraction peaks based on its crystal structure in the powder X-ray diffraction diagram when angles 2θ are at least 121 deg, 175 deg, 21,9 deg, 229 deg and 242 deg

Sertraline hydrochloride methanolated substance and sertraline hydrochloride ethanolated substance and their production

Benzyl alcohol derivatives represented by general formula (I) and a process for producing the same; wherein R1 represents cyano or -COOR2 (wherein R2 represents linear C?1-5? alkyl); and a process for producing from the above benzyl alcohol derivatives intermediates which are useful in producing drugs such as sertraline useful as antidepressant.

Hideto Miyamoto

Papers

Hollow reduction gear

Production of sertraline hydrochloride

Sertraline hydrochloride methanolated substance and sertraline hydrochloride ethanolated substance and their production

Benzyl alcohol derivatives