Rhone-poulenc Rorer S.a.

Aventis Pharma Limited

Aventis Pharma S.a.

Jean-Rene Authelin

Eric Didier

Isabelle Taillepied

Elie Fouque

Michel Lavigne

Bernadette Mandard

Patrik Hosek

Jacques Doveze

Andrew B Brown

Franck Leveiller

Patrick Hosek

Narasimha M Vemuri

The present invention is a method of milling materials to form a fine powder with a median particle size below 10 micrometer which is suitable for inhalation and which has substantially no amorphous content generated during milling. The method is particularly suitable for milling materials which are soft. The method comprises milling the material in a fluid energy mill at reduced temperature using helium, or helium mixed with another gas, as milling fluid. Temperatures of &#x2212;30&#xb0; C. or less are used.

Milling process for the production of finely milled medicinal substances

The invention is an improved method of generating fine medicament powders suitable for inhalation. A fluid energy mill is used with conventional milling fluids such as air or nitrogen. The milling fluid is treated to have a controlled relative humidity of between 30% and 70%. This produces a fine medicament powder with a median particle size below 10 micrometer but with little or no amorphous content generated during milling. Scale formation in the mill chamber is also greatly reduced.

The present invention is directed to 4,10.beta.-diacetoxy-2.alpha.-benzoyloxy-5.beta.,20-epoxy-1-hydroxy-9-oxo- 19-norcyclopropa(g)tax-11-en-13.alpha.-yl (2r,3s)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate dihydrate and a process for its preparation.

4,10-.beta.-diacetoxy-

Process for the preparation of 4-acetoxy-2.alpha.-benzoyloxy-5.beta.,

Method for preparing 4, 10-diacetoxy-2.alpha.-benzoyloxy-5.beta.,

Growing community of inventors

Saint Germain les Arpajon, France

Jean-Rene Authelin