Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
1998-06-18
2002-02-12
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C514S178000, C514S179000, C514S181000, C514S951000, C424S489000, C424S043000, C424S044000, C023S297000, C023S299000, C210S634000, C210S702000, C210S709000, C210S713000, C210S773000, C210S774000, C210S808000
Reexamination Certificate
active
06346523
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention provides finely divided particles of budesonide and a process for their preparation. The invention also relates to 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 a respiratory disorder, and a method of treatment of respiratory disorders by administration of said particles to a host in need of such treatment.
Finely divided particles of budesonide are used in therapy in administration by inhalation where it is desired that the drug particles penetrate deep into the lung. Conventionally these finely divided drug particles are made by techniques such as micronization or grinding. A number of other techniques for their production are also available. Such techniques, and in particular micronization, can produce particles which have regions of partially amorphous structure and which have an irregular shape, but which are generally sufficiently stable for pharmaceutical use. However, these particles are liable to change their structure when kept in an adverse environment, such as is usual when a drug is stored (e.g. in high humidity which can cause agglomeration), and/or is in use by a patient. In the past the problem of the amorphous areas has been overcome by subjecting the particles to a conditioning process such as that disclosed in WO 95/05805 but the problem with the irregular shape of the particles remains. The shape of the particles is important because any irregularity increases the tendency of the particles to stick together. Thus they are harder to disperse in the lung. A solution to these problems has been sought.
SUMMARY OF THE INVENTION
According to the present invention the problem has been solved by providing finely divided, substantially crystalline particles of budesonide characterised in that they are substantially smooth and have a surface area BET gas absorption value of from 1 to 4.5 preferably from 2.0 to 4.5, preferably 2.0 to 3.6 m
2
/g.
The well-defined small particles of the present invention are a prerequisite for an efficient formulation for inhalation, which may be observed by e.g. an increased fraction of the dose to the lung. Crystals with a low surface area have lower tendency to stick together than crystals with a higher surface area e.g irregular crystals.
The surface area was measured by BET gas absorption, e.g. as measured by a Flowsorb II 2300 or Gemini 2370, Micromeritics Co, USA, and described in ISO/TC24SC4N 55 (7th draft) and references therein.
The smoothness of the particles of the invention is illustrated by
FIG. 1
which is a Scanning Electron Micrograph (SEM) of the particles of the invention taken using a JEOL Scanning Microscope JSM-5200.
It is preferred that the finely divided particles according to the invention have a mass median diameter (MMD) of less than 10 &mgr;m, preferably less than 5 &mgr;m, more preferably less than 3 &mgr;m.
The particles according to the invention have a substantially crystalline form, preferably at least 95% by weight crystallinity wherein there are substantially no amorphous areas. The crystallinity of the particles of the invention is illustrated by the X-ray diffraction pattern of FIG.
2
. Preferably the particles of the invention have an energy of recrystallization of less than 1.0 J/g, more preferably less than 0.5 J/g, as measured using a ThermoMetric 227 Thermal Activity monitor. The measurement was carried out by exposing samples of the particles to a temperature of 25° C. and 94% relative humidity for 24 hours and recording the amount of heat given off by the sample.
REFERENCES:
patent: 5254330 (1993-10-01), Ganderton et al.
patent: 5314506 (1994-05-01), Midler, Jr. et al.
patent: 5674860 (1997-10-01), Carling et al.
patent: 5709884 (1998-01-01), Trofast et al.
patent: 5874063 (1999-02-01), Briggner et al.
patent: 0169618 (1986-01-01), None
patent: WO 90/03782 (1990-04-01), None
patent: WO 95/01221 (1995-01-01), None
patent: WO 95/05805 (1995-03-01), None
patent: WO 96/32095 (1996-10-01), None
PCT Search Report (3 pages).
Debendetti et al., “Application of Supercritical Fluids for the Production of Sustained Delivery Devices”, J. of Controlled Release, 24:27-44, 1993.
Phillips et al., “Rapid Expansion From Supercritical Solutions: Application to Pharmaceutical Processes”, Int'l. J. of Pharmaceuticals, 94:1-10, 1993.
Streckel et al, “Micronizing of steroids for pulmonary delivery by supercritical carbon dioxide”, Internat'l J. of Pharmaceutics, 152:99-110, 1997.
Bisrat Mikael
Moshashaee Saeed
AstraZeneca AB
Krass Frederick
LandOfFree
Budesonide particles and pharmaceutical compositions... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Budesonide particles and pharmaceutical compositions..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Budesonide particles and pharmaceutical compositions... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2940517