Schering Aktiengesellschaft

Jenapharm Gmbh & Co. Kg

Bayer Pharma Aktiengesellschaft

Peter Hoesel

Detlef Grawe

Sabine Gliesing

Hagen Gerecke

Uwe Mueller

Annette Eichardt

Michael Dittgen

Carsten Timpe

Michael Sander

Bernd Erhart

Thomas Michel

Robert Eilers

Ulf Tilstam

Peter Moellmann

Dieter Wehmeier

Uwe Knabe

Wilfried Fischer

Klaus Matthey

Michael Mosebach

David Voigtlaender

Jürgen Jacke

Klaus Bahl

Ulf Bohlmann

The present invention relates to a method for the reliable and reproducible preparation of 4-[17&#x3b2;-methoxy-17&#x3b1;-methoxymethyl-3-oxoestra-4,9-dien-11&#x3b2;-yl]benzaldehyde (E)-oxime (asoprisnil) on the pilot and manufacturing scale. Asoprisnil, which is prepared by this method, is distinguished by a very good physical stability and is therefore particularly suitable for the manufacture of solid pharmaceutical forms (tablets, coated tablets, etc.).

Method for preparing 4-[17&#x3b2;-methoxy-17&#x3b1;-methoxymethyl-3-oxoestra-4,9-dien-11&#x3b2;-yl]benzaldehyde (E)-oxime (asoprisnil)

The process for making crystals of a 11 &#x3b2;-benzaldoxim-estra-4,9-diene derivative having an average particle size of from 3 &#x3bc;m to 25 &#x3bc;m and a maximum particle size of 100 &#x3bc;m, includes subjecting a supersaturated solution containing a special 11&#x3b2;-benzaldoxim-estra-4,9-diene derivative of formula (I) to a wet milling by a wet milling apparatus while crystallizing, In order to obtain a primary particle suspension. Crystals obtained according to this process and pharmaceutical preparations containing them are also described and are part of the invention.

Process for production of crystals of 11&#x3bc;-benzaldoxim-estra-4,9-diene derivatives, crystals obtained thereby and pharmaceutical preparations containing them

The process for making steroid crystals having a predetermined average particle size of from 1 &#x3bc;m to 25 &#x3bc;m and a maximum particle size that does not exceed a predetermined maximum value of 100 &#x3bc;m, includes subjecting a supersaturated solution containing a steroid to a wet milling by wet milling apparatus while crystallizing, in order to obtain a primary particle suspension. Crystals obtained according to this process and pharmaceutical preparations containing them are also described.

Process for production of steroid crystals, steroid crystals obtained thereby and pharmaceutical preparations containing them

The transdermal system includes a sex hormone-containing adhesive matrix, which contains inclusions of a sex hormone in a hydrophilic non-crosslinked polymer in dissolved or dispersed form. The inclusions have a concentration of 20 to 90 percent by weight of the sex hormone, which is more than 50 percent by weight amorphous. The hydrophilic non-crosslinked polymer can be polyvinylpyrrolidone, methylcellulose, ethylcellulose or hydroxyethylcellulose. The adhesive matrix can be a polyisobutylene, ethylene-vinyl-acetate copolymer or a polystyrene-butadiene block copolymer.

Laminates containing an active substance transdermal system

A homogeneous steroid-containing preformulation for production of solid and semi-solid pharmaceutical preparations containing a uniform constant dosage of at least one steroid in a range from 0.001 to 1 percent by weight is described. This steroid-containing preformulation contains of from 0.001 to 50 percent by weight of the at least one steroid. The homogeneous steroid-containing preformulation is made by a method including dissolving the at least one steroid in a solvent to form a dispersant; dispersing an adjuvant consisting of adjuvant particles in the dispersant in a mass ratio of the adjuvant to the at least one steroid of,to 1000:1 to form a suspension; and creating a spray-mist of the suspension so as to evaporate and remove the solvent from the suspension and thus to form a dried particulate which includes steroid-containing particles. The droplets in the spray mist have a droplet diameter greater than a mean diameter of the adjuvant particles. The maximum particle size of the dried particulate forming the steroid-containing preformulation is increased by less than 30 percent in comparison to an average particle size of the adjuvant particles.

Homogeneous preformulations containing high concentrations of steroids, for producing low-dose solid and semi-solid pharmaceutical preparations

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Jena, Germany

Peter Hoesel