Oral solid dosage forms containing a low dose of estradiol

A solid dosage form, estradiol technology, applied in the field of oral solid dosage forms, can solve problems such as being unsuitable for oral administration

Inactive Publication Date: 2007-12-26
BAYER SCHERING PHARMA OY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This vaginal composition is also n

Method used

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  • Oral solid dosage forms containing a low dose of estradiol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Example 1 - In Vitro Dissolution of Micronized Estradiol

[0104] The dissolution profiles of micronized estradiol and mixtures of micronized estradiol and polyvinylpyrrolidone were tested in an in vitro dissolution test system. The dissolution tester uses USP apparatus 2 (paddle system) (see USP 27), using 900ml of purified water at a temperature of 37°C as the dissolution medium, and the rotation speed is 50rpm. Estradiol and mixture in powder form in an amount equivalent to 100 μg of micronized estradiol hemihydrate were placed in the dissolution vessel.

[0105] Table 1. Dissolution test results

[0106] powder ingredients

following time

Dissolution amount of estradiol (μg):

5min

10min

20min

30min

60min

100 μg estradiol

100μg estradiol + 100μg

Polyvinylpyrrolidone

100μg Estradiol + 4mg

Polyvinylpyrrolidone

＜3 *

16

19

＜3 *

29

47

＜3 *

48 ...

Embodiment 2

[0109] Example 2- Preparation of Oral Solid Dosage Form of Low Dose Estradiol

[0110] Prepare 80 mg tablet cores with the following composition:

[0111] Element:

Quantity (mg):

I Estradiol (hemihydrate, micronized)

II lactose monohydrate

III corn starch

IV modified starch (corn)

V corn starch

VI magnesium stearate

0.05

not higher than 80mg

14.40

9.60

2

0.80

0.1

not higher than 80mg

14.40

9.60

2

0.80

0.19

not higher than 80mg

14.40

9.60

2

0.80

[0112] The corn starch marked "V" may be replaced with another "second choice" binder, eg (low substituted) hydroxypropyl cellulose in an amount of 1.6 mg.

[0113] Oral solid dosage forms are prepared by adding ingredients I-IV (estradiol, lactose monohydrate, corn starch, and modified starch) to a fluid bed granulator and starting the fluid bed. The aqueous solution of ingredient V (corn starch) was t...

Embodiment 3

[0114] Example 3 - Stability of low dose estradiol dosage forms

[0115] The chemical stability of estradiol (semi-hydrated and micronized) in three different tablet formulations A, B and C was tested in the dark at 40°C and 75% relative humidity for 12 months. Keep tablets in an airtight container during storage.

[0116] At the start of the stability study, the three tablet formulations (A, B, and C) contained a labeled value of 0.05 mg of micronized estradiol hemihydrate and were supplied with hydroxypropylcellulose, polyethylene glycol , talc, titanium dioxide and iron oxide pigment yellow coating film. The 80 mg tablet core has the following composition ("+" indicates the presence of a given component):

[0117] Element

Quantity (mg)

A

B

C

I Estradiol (hemihydrate, micronized)

II lactose monohydrate

III corn starch

IV modified starch (corn)

V corn starch

V polyvinylpyrrolidone

V hydroxypropyl cellulose

VI magnesi...

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PUM

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Abstract

The present invention relates to oral solid dosage forms containing a very low dose of estradiol. The dosage forms are formulated in a manner so as to avoid degradation of the estradiol and to minimise the content of polyvinylpyrrolidone, while still achieving similar fast dissolution of the estradiol. The dosage forms are useful in preventing or treating a physical condition in a woman caused by insufficient endogenous levels of estradiol.

Description

field of invention [0001] The present invention relates to a pharmaceutical composition containing low-dose estradiol, in particular to an oral solid dosage form containing low-dose estradiol. The dosage form of the invention allows good chemical stability of estradiol during storage while also achieving a high dissolution rate of estradiol in water. Background of the invention [0002] Pharmaceutical dosage forms containing steroid hormones of natural or synthetic origin usually contain low doses of these active ingredients. In the present invention, the dose of estradiol is significantly lower than the dose administered orally so far in the treatment of physical conditions associated with insufficient endogenous estrogen levels in women. [0003] According to US 5,891,868 (Cummings et al.), the risk of bone fractures in postmenopausal women is reduced by daily transdermal administration of about 20 μg of estradiol or even less than about 20 μg of estradiol. Transdermal a...

Claims

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Application Information

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IPC IPC(8): A61K9/20A61K31/565
CPCA61K9/2018A61K9/2054A61K9/2027A61K9/2059A61P1/08A61P15/12A61P19/00A61P19/08A61P19/10A61P25/02A61P25/04A61P25/06A61P25/24A61P43/00A61P5/00A61P5/24A61P5/30A61K9/28
Inventor A·丰克K·米勒T·瓦格纳C·祖尔特
Owner BAYER SCHERING PHARMA OY
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