H. Lundbeck A/s

Hans Petersen

Michael Harold Rock

Robert Dancer

Haleh Ahmadian

Ole Nielsen

Ken Liljegren

Poul Dahlberg Nielsen

Helle Eliasen

Rikke E Humble

Michael Bech Sommer

Peter Ellegaard

Yasuyoshi Ueda

Jakob Felding

Takashi Yoshida

Klaus P Bogeso

Toshihiro Takeda

Leone Dall'Asta

Takahisa Kato

Peter Bregnedal

Lars Ole Lyngso

Troels Volsgaard Christensen

Shogo Yamamoto

Umberto Casazza

Klaus Peter B&oslash;ges&oslash;

Martin Markvard Knudsen

Brian Christiansen

Jesper Tungelund Larsen

Naoki Taoka

Rikke Eva Humble

Klaus Peter Bögesö

Per Holm

An injectable pharmaceutical composition comprising carbamazepine and sulfobutylether-7-&#x3b2;-cyclodextrin, wherein said composition is essentially free of 10-Br-carbamazepine, is disclosed. Methods for the manufacture of said composition and methods for treatment of disease using said composition are also disclosed.

Injectable carbamazepine composition essentially free of 10-bromo-carbamazepine

A process for the manufacture of vortioxetine HBr &#x3b1;-form is provided.

Process for the manufacture of vortioxetine HBr alpha-form

The present invention is concerned with a process in connection with the purification of a pharmaceutically acceptable salt of escitalopram or citalopram.

Process for the purification of pharmaceutically acceptable salts

The present invention relates to a novel method for the preparation of diol intermediates having the formula (II) and/or the opposite enantiomer of an acylated diol having the formula (IV) useful for the preparation of escitalopram involving selective enzymatic acylation or deacylation. 

Method for the separation of intermediates which may be used for the preparation of escitalopram

The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100&#xb0; C., as well as a method for making such an orodispersible tablet.

Crystalline base of escitalopram and orodispersible tablets comprising escitalopram base

The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100&#xb0; C., as well as a method for making such an orodispersible tablet.

In the following, citalopram diol means 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)-benzonitrile, as free base and/or acid addition salt. The invention relates to a process for the preparation of racemic citalopram diol and/or R- or S-citalopram diol, comprising the separation of a non-racemic mixture of R- and S-citalopram diol with more than 50% of one of the enantiomers into a fraction being enriched with S- or R-citalopram diol and a fraction comprising RS-citalopram diol wherein the ratio of R-citalopram diol:S-citalopram diol is equal to 1:1 or closer to 1:1 than in the initial mixture. The method is characterized in that (i) RS-citalopram diol is precipitated from a solution of the initial non-racemic mixture, or R- or S-citalopram diol is dissolved into a solvent from the initial non-racemic mixture, leaving a residue of RS-citalopram diol, and in that (ii) the residue/precipitate formed is separated from the final solution phase, followed by optional steps of repetition, recrystallisation, purification, isolation and conversion between free base and salts. The invention also relates to a process for the preparation of RS-citalopram, S-citalopram or R-citalopram (all as free base and/or acid addition salt) comprising the method described above followed by ring closure.

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The present invention relates to a new method of preparing gaboxadol (THIP), which is useful for treating sleep disorders. In particular a method of preparing THIP comprising reacting a compound of formula (8b) or a salt thereof with an acid, typically a mineral acid, to obtain THIP as an acid addition salt. The present invention also relates to several intermediates 

Method for manufacture of THIP

The invention provides a new and improved method for the preparation of 5-cyano-phtalid, which is a key intermediate in the preparation of the antidepressant compound citalopram.

Method for the preparation of citalopram

The invention relates to a process for the preparation of racemic citalopram free base or an acid addition salt thereof and/or R- or S-citalopram as the free base or an acid addition salt thereof by separation of a mixture of R- and S-citalopram with more than 50% of one of the enantiomers into a fraction consisting of racemic citalopram and/or a fraction of S-citalopram or R-citalopram characterized in that i) citalopram is precipitated from a solvent as the free base or as an acid addition salt thereof; ii) the precipitate formed is separated from the mother liquor; iia) if the precipitate is crystalline it is optionally recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iib) if the precipitate is not crystalline, steps i) and ii) are optionally repeated until a crystalline precipitate is obtained and the crystalline precipitate is recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iii) the mother liquor is optionally subjected to further purification and S-citalopram or R-citalopram is isolated from the mother liquor and optionally converted into an addition salt thereof.

Process for the preparation of racemic citalopram and/or S-or R-citalopram by separation of a mixture of R-and S-citalopram

A method for the preparation of citalopram comprising reductive hydrolysis of a compound of Formula (IV)wherein R is a N,N-disubstituted amid group or an optionally substituted 4,5-dihydro-1,3-oxazol-2-yl group, and conversion of the resulting 5-formyl compound to citalopram.

The present invention relates to a method for the preparation of citalopram by alkylation of a 1-(4-fluorophenyl)-1,3-dihydroisobenzofurane derivative.

A method for the preparation of 5-cyanophthalide comprising treatment of a compound of formula IVwherein X is O or S;

Method for the preparation of 5-cyanophthalide

5-carboxyphthalide is obtained with very high purity and in high yields by a convenient process comprising reaction of terephthalic acidwith paraformaldehyde HO(CH)H in oleum.

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Vanløse, Denmark

Hans Petersen