Progestin co-micronized with a surfactant, pharmaceutical composition comprising same, methods for making same and uses thereof

Abstract

The invention concerns a progestin co-micronized with a surfactant and a pharmaceutical composition comprising said gestagenic. The invention also concerns methods for preparing same.

Description

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

[0001] This application claims priority under 35 U.S.C. § 119 to French Application 0102814, filed Mar. 1, 2001. This application is a continuation of U.S. application Ser. No. 10 / 469,441, filed Feb. 10, 2004, which is incorporated herein by reference in its entirety, and which is the U.S. National Stage of PCT / FR02 / 00714, filed Feb. 27, 2004. This application claims priority under 35 U.S.C. § 120 to these U.S. and PCT applications.FIELD OF THE INVENTION

[0002] The present invention relates, as a new product, to a progestin co-micronized with a surfactant, to a pharmaceutical composition containing same, to methods for preparing same, and also to uses thereof. BACKGROUND OF THE INVENTION

[0003] In the context of the present invention, the term “progestin” is intended to mean any steroid having affinities for progesterone receptors and capable of more or less fully reproducing the biological effects of progesterone.

[0004] A progestin is...

Examples

example 1

Preparation of Progesterone Co-Micronized with Sodium Lauryl Sulfate

[0067] 1) 97 g of progesterone and 3 g of sodium lauryl sulfate are mixed for 5 minutes in a mixer of the LÖDIGE type.

[0068] 2) The mixture obtained in step (1) is introduced into an Alpine 200 AS airjet mill preset on the following parameters: [0069] injection: 5.5 B [0070] ring: 3.0B [0071] rate: 35 kg / h

[0072] 3) This mixture is ground in order to obtain a co-micronized material of progesterone / sodium lauryl sulfate.

example 2

Tablets Based on Progesterone Co-Micronized with A Surfactant

[0073] The formulations of progesterone tablets according to the invention, containing 100 and 200 mg of progesterone, are given in Table I below.

TABLE 1NAME OF THEUNIT AMOUNTBATCHCOMPONENTFUNCTIONmg / tabletSIZE (kg)MicronizedActive55.000progesterone*principle(sodium lauryl(progestin)200100sulfate (SLS))*(surfactant)6.183.09Povidone K30Binder9.604.802.561Solution at35% (m / m)MannitolDiluent29.8414.927.981CrosslinkedDisintegrating13.006.503.468sodiumagentcarboxymethylcelluloseMagnesiumLubricant1.300.650.347stearate

*Progesterone / SLS are co-micronized according to example 1.

[0074] To prepare the tablets in question, the following procedure was carried out:

Step 1: Preparation of the Wetting Solution

[0075] 4.756 kg of purified water are introduced into a container of suitable volume. 2.561 kg of Povidone K30 are then introduced into the purified water, gradually, and with stirring in a deflocculating-type stirrer (RAYNERI)...

example 3

Dissolving of the Progesterone Tablets Prepared According to the Invention, In Vitro

[0103] 100 mg and 200 mg progesterone tablets are prepared according to the method given in example 2, and the following operations are carried out in order to determine the in vitro dissolution curves (see FIG. 1).

[0104] The following material is used: [0105] SOTAX AT7 7-position revolving-paddle dissolution device [0106] PERKIN ELMER lambda 20 spectrophotometer [0107] ISMATEC IPC 12 cassette pump [0108] WINSOTAX data acquisition software.

[0109] The dissolving conditions are as follows: [0110] dissolving medium: 1000 ml of aqueous solution of β-hydroxypropylcyclodextrin having the trade mark KLEPTOSE® at 1% per cell [0111] rotation rate: 150 rpm [0112] temperature: 37° C.±0.5° C. [0113] number of cells: 7 [0114] circulation cell made of quartz with an optical path: 0.1 cm.

[0115] A control is prepared, consisting of a tablet of micronized progesterone:

Progesterone20mgHPLC ethanol20ml1% solution...

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

[0001] This application claims priority under 35 U.S.C. § 119 to French Application 0102814, filed Mar. 1, 2001. This application is a continuation of U.S. application Ser. No. 10 / 469,441, filed Feb. 10, 2004, which is incorporated herein by reference in its entirety, and which is the U.S. National Stage of PCT / FR02 / 00714, filed Feb. 27, 2004. This application claims priority under 35 U.S.C. § 120 to these U.S. and PCT applications.FIELD OF THE INVENTION

[0002] The present invention relates, as a new product, to a progestin co-micronized with a surfactant, to a pharmaceutical composition containing same, to methods for preparing same, and also to uses thereof. BACKGROUND OF THE INVENTION

[0003] In the context of the present invention, the term “progestin” is intended to mean any steroid having affinities for progesterone receptors and capable of more or less fully reproducing the biological effects of progesterone.

[0004] A progestin is...

Examples

example 1

Preparation of Progesterone Co-Micronized with Sodium Lauryl Sulfate

[0067] 1) 97 g of progesterone and 3 g of sodium lauryl sulfate are mixed for 5 minutes in a mixer of the LÖDIGE type.

[0068] 2) The mixture obtained in step (1) is introduced into an Alpine 200 AS airjet mill preset on the following parameters: [0069] injection: 5.5 B [0070] ring: 3.0B [0071] rate: 35 kg / h

[0072] 3) This mixture is ground in order to obtain a co-micronized material of progesterone / sodium lauryl sulfate.

example 2

Tablets Based on Progesterone Co-Micronized with A Surfactant

[0073] The formulations of progesterone tablets according to the invention, containing 100 and 200 mg of progesterone, are given in Table I below.

TABLE 1NAME OF THEUNIT AMOUNTBATCHCOMPONENTFUNCTIONmg / tabletSIZE (kg)MicronizedActive55.000progesterone*principle(sodium lauryl(progestin)200100sulfate (SLS))*(surfactant)6.183.09Povidone K30Binder9.604.802.561Solution at35% (m / m)MannitolDiluent29.8414.927.981CrosslinkedDisintegrating13.006.503.468sodiumagentcarboxymethylcelluloseMagnesiumLubricant1.300.650.347stearate

*Progesterone / SLS are co-micronized according to example 1.

[0074] To prepare the tablets in question, the following procedure was carried out:

Step 1: Preparation of the Wetting Solution

[0075] 4.756 kg of purified water are introduced into a container of suitable volume. 2.561 kg of Povidone K30 are then introduced into the purified water, gradually, and with stirring in a deflocculating-type stirrer (RAYNERI)...

example 3

Dissolving of the Progesterone Tablets Prepared According to the Invention, In Vitro

[0103] 100 mg and 200 mg progesterone tablets are prepared according to the method given in example 2, and the following operations are carried out in order to determine the in vitro dissolution curves (see FIG. 1).

[0104] The following material is used: [0105] SOTAX AT7 7-position revolving-paddle dissolution device [0106] PERKIN ELMER lambda 20 spectrophotometer [0107] ISMATEC IPC 12 cassette pump [0108] WINSOTAX data acquisition software.

[0109] The dissolving conditions are as follows: [0110] dissolving medium: 1000 ml of aqueous solution of β-hydroxypropylcyclodextrin having the trade mark KLEPTOSE® at 1% per cell [0111] rotation rate: 150 rpm [0112] temperature: 37° C.±0.5° C. [0113] number of cells: 7 [0114] circulation cell made of quartz with an optical path: 0.1 cm.

[0115] A control is prepared, consisting of a tablet of micronized progesterone:

Progesterone20mgHPLC ethanol20ml1% solution...

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