Solid dispersions of selective progesterone receptor modulators

Abstract

The subject of the present invention is a solid dispersion comprising an active ingredient selected from selective progesterone receptor modulators, their metabolites and mixtures thereof and a pharmaceutically acceptable polymeric excipient. The invention also relates to pharmaceutical compositions comprising said solid dispersions and their therapeutic use.

Description

technical field

[0001] The present invention relates to novel galenic forms of selective progesterone receptor modulators (SPRMs), more particularly to solid dispersions and pharmaceutical compositions containing said galenical forms. Background technique

[0002] Ulipristal acetate (abbreviated as UPA) corresponds to 17α-acetoxy-11β-[4-(N,N-dimethylamino)phenyl]-19-norpregna-4,9-diene- 3,20-Diketones (IUPAC nomenclature) and have the following chemical formula:

[0003]

[0004] Its synthesis is described inter alia in patent EP 0 422 100 and in patent application EP 1602 662 .

[0005] Ulipristal acetate is a synthetic selective progesterone receptor modulator (SPRM). Ulipristal acetate acts as a contraceptive by inhibiting or delaying ovulation by virtue of its action on progesterone receptors. Clinical studies have shown that ulipristal acetate administered in a single dose of 30 mg makes it possible to prevent unwanted pregnancy when administered within 120 hours ...

Examples

Embodiment 1

[0209] Example 1: Preparation and evaluation of various solid dispersions

[0210] 1. Preparation according to the solid dispersion of the present invention

[0211] a) Preparation of solid dispersions by means of the melting method

[0212] A solid dispersion comprising ulipristal acetate as an active ingredient and polyethylene glycol (PEG-4000) as a polymer excipient was prepared in the following manner, wherein the "polymer excipient / UPA" weight ratio was 960 / 40 :

[0213] - heat the polyethylene glycol until it is completely melted,

[0214] - Add micronized UPA to molten PEG with stirring. Heat the mixture and keep stirring until the UPA is completely dissolved,

[0215] - bring the mixture to ambient temperature with stirring,

[0216] - Optionally milling and micronizing the obtained solid dispersion to obtain the desired particle size distribution.

[0217] Other solid dispersions are also prepared by means of the melt method:

[0218] - UPA with weight ratio...

Embodiment 2

[0263] Example 2: Pharmaceutical composition integrating a solid dispersion according to the invention

[0264] Tables 3 and 4 below provide examples of pharmaceutical compositions according to the invention. These pharmaceutical compositions can be obtained by mixing the solid dispersion according to the invention with various excipients and then shaping the mixture by direct compression to obtain tablets.

[0265] Table 3: Examples of compositions according to the invention comprising 5 mg UPA

[0266]

[0267] The composition can be used, for example, in the treatment of uterine fibroids.

[0268] Table 4: Examples of compositions according to the invention comprising 30 mg UPA

[0269]

[0270] The composition is useful, for example, in emergency contraception.

technical field

[0001] The present invention relates to novel galenic forms of selective progesterone receptor modulators (SPRMs), more particularly to solid dispersions and pharmaceutical compositions containing said galenical forms. Background technique

[0002] Ulipristal acetate (abbreviated as UPA) corresponds to 17α-acetoxy-11β-[4-(N,N-dimethylamino)phenyl]-19-norpregna-4,9-diene- 3,20-Diketones (IUPAC nomenclature) and have the following chemical formula:

[0003]

[0004] Its synthesis is described inter alia in patent EP 0 422 100 and in patent application EP 1602 662 .

[0005] Ulipristal acetate is a synthetic selective progesterone receptor modulator (SPRM). Ulipristal acetate acts as a contraceptive by inhibiting or delaying ovulation by virtue of its action on progesterone receptors. Clinical studies have shown that ulipristal acetate administered in a single dose of 30 mg makes it possible to prevent unwanted pregnancy when administered within 120 hours ...

Examples

Embodiment 1

[0209] Example 1: Preparation and evaluation of various solid dispersions

[0210] 1. Preparation according to the solid dispersion of the present invention

[0211] a) Preparation of solid dispersions by means of the melting method

[0212] A solid dispersion comprising ulipristal acetate as an active ingredient and polyethylene glycol (PEG-4000) as a polymer excipient was prepared in the following manner, wherein the "polymer excipient / UPA" weight ratio was 960 / 40 :

[0213] - heat the polyethylene glycol until it is completely melted,

[0214] - Add micronized UPA to molten PEG with stirring. Heat the mixture and keep stirring until the UPA is completely dissolved,

[0215] - bring the mixture to ambient temperature with stirring,

[0216] - Optionally milling and micronizing the obtained solid dispersion to obtain the desired particle size distribution.

[0217] Other solid dispersions are also prepared by means of the melt method:

[0218] - UPA with weight ratio...

Embodiment 2

[0263] Example 2: Pharmaceutical composition integrating a solid dispersion according to the invention

[0264] Tables 3 and 4 below provide examples of pharmaceutical compositions according to the invention. These pharmaceutical compositions can be obtained by mixing the solid dispersion according to the invention with various excipients and then shaping the mixture by direct compression to obtain tablets.

[0265] Table 3: Examples of compositions according to the invention comprising 5 mg UPA

[0266]

[0267] The composition can be used, for example, in the treatment of uterine fibroids.

[0268] Table 4: Examples of compositions according to the invention comprising 30 mg UPA

[0269]

[0270] The composition is useful, for example, in emergency contraception.

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