Crystalline S-(fluoromethyl) (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a] phenanthrene-17-carbothioate and process for preparation thereof (17-Nov-2009)

Crystalline S-(fluoromethyl) (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro- 11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16- octahydrocyclopenta[a] phenanthrene-17-carbothioate and process for preparation thereof

  S-(fluoromethyl) (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17- dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a] phenanthrene-17-carbothioate (referred as FLF) of the following chemical structure:

F

is a synthetic corticosteroid. FLF is marketed under the trade name Veramyst® used for the treatment of asthma, allergic rhinitis, optionally in combination with salmeterol

New crystalline forms were found and are described herein below.

FLF Crystalline Form N

  The crystalline form of FLF, designated form N, is characterized by data selected from a group consisting of at least one of: powder XRD pattern having peaks at about
10.7, 12.4, 24.5 and 24.7 ± 0.2 degrees two-theta; a PXRD pattern depicted in Figure 1; and any combination thereof.

O

S O

O

O

H

O

F

F

O

Figure 1: A PXRD pattern of crystalline FLF form N

  The above crystalline form N can be further characterized by data selected form a group consisting of: a powder XRD pattern having peaksat about 15.0, 16.2, 17.3,
17.7, 18.7 and 21.4 ± 0.2 degrees two-theta; a weight loss of up to about 16.7% at a temperature of about 25ºC to about 92ºC as measured by TGA; and any combination thereof.

  According to the above described data, the above form N of FLF is a glycerol formal solvate.

FLF Crystalline Form P

  The crystalline form of FLF, designated form P, is characterized by data selected from a group consisting of at least one of: powder XRD pattern having peaks at about
14.1, 15.1, 15.3, 17.0 and 17.4 ± 0.2 degrees two-theta; a PXRD pattern depicted in Figure 2; and any combination thereof.

Figure 2: A PXRD pattern of crystalline FLF form P

  The above crystalline form P can be further characterized by data selected form a group consisting of: a powder XRD pattern having peaksat about 12.2, 21.2, 21.4,
24.5 and 25.6 ± 0.2 degrees two-theta; a weight loss of up to about 13.5% at a temperature of about 27ºC to about 109ºC as measured by TGA that corresponds to a theoretical 1:1 ratio of 2-methyl-tetrahydrofuran vs. FLFin the solvated form; and any combination thereof.

  According to the above described data, the above form P of FLF is a 2-methyl tetrahydrofuran solvate.

FLF Crystalline Form R

  The crystalline form of FLF, designated form R, is characterized by data selected from a group consisting of at least one of: powder XRD pattern having peaks at about
9.5, 10.9, 19.0 and 28.7 ± 0.2± 0.2 degrees two-theta; a PXRD pattern depicted in Figure 3; and any combination thereof.