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Wafer Comprising Steroid Hormones

a technology of steroid hormones and wafers, applied in the direction of medical preparations, pharmaceutical delivery mechanisms, endocrine system disorders, etc., can solve the problems of poor solubility or absorption, thick wafers disintegration, low bioavailability of active ingredients, etc., and achieve high bioavailability

Inactive Publication Date: 2017-12-07
LTS LOHMANN THERAPIE-SYST AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides an administration system that can dissolve in the mouth for steroid hormones that are not easily absorbed through the digestive tract. The system contains a steroid hormone and a carrier material, which helps to release the hormone quickly and with high bioavailability. The maximum blood level of the hormone is reached within 60 minutes. The carrier material can be selected from a wide range of options, including cellulose and its derivatives, starch, and gelatin. This invention offers a convenient and effective way to deliver steroid hormones for therapeutic purposes.

Problems solved by technology

Poor solubility or absorption cannot be compensated by enlarging the wafer at will, because the size of the wafer is limited by the size of the mouth, and thick wafers disintegrate only very slowly.
A major problem in the development of buccal and sublingual administration systems is, however, the low active ingredient flux rate through the mucosal epithelial tissue, which leads to a low bioavailability of the active ingredient.
However, the steroid hormones described herein cannot readily be converted into a salt form.
In the concentration necessary for increasing the mucosal absorption, however, the use of many known permeation enhancers potentially led to irritation and / or damage of the mucosal membranes.
Since permeation enhancers by definition damage the mucosa, the serious disadvantages of enhancing permeation with such permeation enhancers include destruction of the buccal mucosa for example through loss of the upper layers of cells and the decrease in the number of desmosomes, and the irritation of the buccal epithelium by salts, sodium lauryl sulfate or bile acids.
Since administration systems in film form for buccal application are limited both in the area and in the thickness, a bioavailability of 25% is inadequate for some steroids.
It is also not readily possible by increasing the loading of the wafers or by excessive “thickening” of the wafer to achieve a higher concentration of dissolved active ingredient at the absorption site (buccal mucosa), because the risk of unwanted swallowing of the active ingredient due to newly formed saliva is increased thereby.
Nor does the use of a sequence of buccally applied films with low availabilities serve the purpose of a fast onset of action.
The active ingredient is subject there, as on oral administration, to the disadvantages of slow uptake and the metabolic first-pass effect.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0041] 5 g of MENT are added to 700 ml of an ethanol / water (50:50) solution and stirred until dissolution is complete. The dissolution is assisted where appropriate by application of ultrasound. 95 g of hydroxypropylmethylcellulose (HPMC) are then added, and the mixture is stirred until dissolution is complete. The mixture is degassed, spread out with the aid of a spreading box and dried. A thin transparent film which is between 50 and 100 μm thick is produced. Transparent wafers with a content of 1.5 mg of MENT are obtained by cutting out samples of appropriate size.

example 2

[0042] 3 g of menthol and 2 g of thymol are added to 26 g of ATMOS 300 (=a mixture of mono- and diglycerides of oleic acid) and 4 g of Tween 80 (=a polyoxyethylene sorbitan oleate ester). The mixture is stirred until the solids have dissolved. Then 5 g of MENT are added to this mixture, which is stirred until the active ingredient has completely dissolved. 60 g of HPMC are added to 600 g of a 50:50 ethanol-water mixture and stirred until dissolution is complete. The organic phase is then added slowly and with high-speed stirring to the aqueous phase, resulting in a thick, creamy composition. Degassing of the mixture and spreading out are followed by drying. A thin translucent film which is between 50 and 100 μm thick is produced. Translucent wafers with a content of 1.5 mg of MENT are obtained by cutting out samples of appropriate size.

example 3

[0043] 5 g of MENT are added to a mixture of 20 g of ATMOS 300, 10 g of octanol and 5 g of lecithin. The mixture is stirred until the solids have dissolved. 60 g of HPMC are added to 600 g of water and stirred until dissolved. The organic phase is added with high-speed stirring to the aqueous phase, resulting in a thick creamy composition. Degassing of the mixture and spreading out are followed by drying. A thin translucent film which is between 50 and 100 μm thick is produced. Translucent wafers with a content of 1.5 mg of MENT are obtained by cutting out samples of appropriate size.

TABLE 1Compositions of dried MENT wafersMENTHPMCATMOS 300 Tween 80 OctanolLecithinMentholThymolExample(%)(%)(%)(%)(%)(%)(%)(%)1595——————2560264——32356020—105——

[0044]It may be noted that the dried systems of example 1 comprise the steroid hormone dissolved as a monomolecular dispersion in the carrier material, whereas the steroid hormone in examples 2 and 3 is in the form of a solution in an oil phase wh...

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PUM

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Abstract

The invention relates to a pharmaceutical composition in the form of a system in film form for transmucosal administration of steroid hormones. An administration system for steroid hormones which dissolves in the mouth and which releases with a high bioavailability is disclosed. The administration system in film form dissolves in the mouth preferably in a period of less than 30 min, and the steroid hormone entering the bloodstream transmucosally from the administration system leads to a rapid rise in the concentration in the blood. It is thus possible to achieve a maximum concentration of this steroid hormone in the blood in a period of less than 60 min after administration.

Description

[0001]The present application is a continuation of U.S. patent application Ser. No. 11 / 391,646 filed on Mar. 28, 2006, the disclosure of which is incorporated herein by reference in its entirety, which claims priority from German Patent Application No. DE 10 2005 015 128.0 filed on Mar. 31, 2005.FIELD OF THE INVENTION[0002]The invention relates to a pharmaceutical composition in the form of a system in film form for transmucosal administration of steroid hormones.[0003]Various administration forms of steroid hormones have been described. Besides conventional oral administration, also available are implants, patches and gels. These administration forms aim at continuous delivery of the steroid hormones which is as uniform as possible over a lengthy period. However, for various applications, an administration leading a rapid rise in the concentration of the steroid hormone in the blood would be desirable. In order for example in a case of male testosterone deficiency to restore the ph...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/56A61K31/568
CPCA61K31/568A61K31/56A61P1/02A61P43/00A61P5/24A61P5/26A61P5/30A61P5/34A61P5/38A61P5/40A61P5/44A61K9/00
Inventor KRUMME, MARKUSRADLMAIER, ALBERTGENERAL, SESCHADITTGEN, MICHAELJENSEN, KEITH
Owner LTS LOHMANN THERAPIE-SYST AG