Title:  Budesonide particles and pharmaceutical compositions containing them

United States Patent:  6,468,994

Issued:  October 22, 2002

Inventors:  Bisrat; Mikael (Sodertalje, SE); Moshashaee; Saeed (Sodertalje, SE)

Assignee:  AstraZeneca AB (Sodertalje, SE)

Appl. No.:  992940

Filed:  November 6, 2001

The invention provides finely divided, substantially crystalline particles of budesonide characterized in that they are substantially smooth and having a BET value of from 1 to 4.5 m2/g, a process for their preparation, a pharmaceutical composition comprising said particles, the use of said particles in the treatment of and in the manufacture of a medicament for use in the treatment of respiratory disorder, and a method of treatment of respiratory disorders by administration of said particles to a host in need of such treatment.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The finely divided particles of the invention may be prepared by the co-introduction of (a) a solution of budesonide in a solvent and (b) a supercritical fluid into an apparatus, wherein the temperature and pressure of the apparatus are controlled such that dispersion and extraction of the solvent by the action of the supercritical fluid occur substantially simultaneously. Thus the active substance, budesonide, precipitates directly into small respirable particles having the desired physio-chemical properties. A supercritical fluid is, in general, a fluid at or above both its critical pressure and critical temperature; it is preferably carbon dioxide. The solvent used to dissolve budesonide is preferably an organic solvent, e.g., acetone or methanol. Preferably the process is carried out using the apparatus disclosed in WO 95/01221.

The finely divided particles according to the invention are preferably for use in the treatment of a respiratory disorder, e.g. asthma. The invention further provides a pharmaceutical composition comprising finely divided particles according to the invention in association with a pharmaceutically acceptable carrier or diluent, e.g. lactose. The invention also provides the use of the finely divided particles according to the invention in the manufacture of a medicament for use in the treatment of a respiratory disorder.

The finely divided particles according to the invention may be used in a variety of pharmaceutical formulations, e.g. in producing tablets, or for filling into capsules for oral use. Preferred, however, are finely divided particles to be used to produce inhalation formulations. Thus the finely divided particles according to the invention may be used on their own or in admixture with excipients, e.g. lactose, which are of a larger, or approximately of the same, particle size as the drug. Such powder formulations may be used in capsules, e.g. for use in the Spinhaler.RTM., or in other inhalation devices, e.g. the Turbuhaler.RTM., the Rotahalere.RTM., the Diskhaler.RTM. or Diskus.RTM.. The finely divided particles according to the invention may also be treated further using known techniques, e.g. spheronization, to provide soft pellets, or soft granules, which are sufficiently strong to be filled into containers without disintegrating, but which are sufficiently weak to disintegrate into their fine constituent particles when administered by inhalation.

Claim 1 of 13 Claims

What is claimed is:

1. A powder comprising finely divided, substantially crystalline particles of budesonide, said particles being smooth and having a BET value from 1 to 4.5 m² /g.
 

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