Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Patent
1991-02-14
1993-04-20
Rose, Shep K.
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
12820315, 424 43, 424452, 424489, 514636, 514826, 514951, 514962, A61K 914, A61K 948, A61K 972
Patent
active
052041131
DESCRIPTION:
BRIEF SUMMARY
PHARMACEUTICAL COMPOSITIONS CONTAINING PENTAMIDINE
This invention relates to pharmaceutical compositions containing pentamidine in powdered form and suitable for administration by inhalation.
BACKGROUND TO THE INVENTION
Pneumo-cystis carinii pneumonia (PCP) is commonly contracted by patients suffering from acquired immuno-deficiency syndrome (AIDS) and also by cancer and organ transplant patients. It has been estimated that some 65% of AIDS patients develop PCP. Amongst such patients the condition is life-threatening.
1,5-Di(4-amidinophenoxy)pentane, which is generically known as pentamidine, has for many years been known for use as a pharmaceutical, in particular for the treatment of the early stages of African trypanosomiasis (`sleeping sickness`). Pentamidine has also been found to be effective in the treatment of PCP infection in AIDS patients when administered by intravenous infusion or intramuscular injection although this treatment is often accompanied by severe side-effects, e.g. hypotension, renal failure and hypoglycaemia. More recently, there has been a report (Abstracts of the Annual Meeting of the American Society of Microbiology 86,14 (1986)) of the prevention of PCP by inhalation of an aerosol spray containing pentamidine or a pharmaceutically acceptable salt thereof. This report, however, relates only to aerosols formed by nebulisation of aqueous solutions.
We have now surprisingly found that pentamidine is effective in the prevention or treatment of PCP when administered by inhalation in powdered form and that formulation of the drug in this way offers certain advantages.
SUMMARY OF THE INVENTION
According to the invention we provide a pharmaceutical composition suitable for administration by inhalation and containing pentamidine, or a pharmaceutically acceptable salt thereof (hereinafter referred to as the active ingredient), in powder form.
Pharmaceutically acceptable salts of pentamidine which may be mentioned are the isethionate, the naphthoate and the mesylate.
We also provide finely divided pentamidine with a mass median diameter in the range 0.01 to 10 microns.
According to another aspect of the invention, there is provided a method for the prevention or treatment of PCP which comprises administration by inhalation to a patient having or susceptible to that condition of a therapeutically effective quantity of pentamidine, or a pharmaceutically acceptable salt thereof, in powder form.
According to another aspect of the invention, there is provided the use of pentamidine, or a pharmaceutically acceptable salt thereof, as active ingredient in the manufacture of a medicament for use in the treatment of PCP, characterized in that the medicament contains pentamidine in powdered form.
DETAILED DESCRIPTION OF THE INVENTION
The composition according to the invention may be a non-pressurised powder composition or a pressurised aerosol composition containing a pharmaceutically acceptable liquefied gas aerosol propellant.
For pressurised aerosol compositions, the active ingredient is preferably finely divided, e.g. having a mass median diameter in the range 0.01 to 10 microns. We particularly prefer the active ingredient to have a mass median diameter of less than 4 microns and especially of less than 3.0 microns and most preferably of less than 2.8 microns. We also prefer not more than 5% by weight of the particles to have a diameter of greater than 10 microns, and more preferably not less than 90% by weight of the particles to have a diameter of less than 6 microns.
We prefer pressurised aerosol compositions to contain from 0.5 to 12%, more preferably from 0.5 to 10%, and most preferably from 0.5 to 5%, e.g. about 1 to 3.5% by weight of finely divided active ingredient.
By mass median diameter we mean the diameter such that half the particulate mass is in particles of lesser diameter and half in particles of greater diameter. The mass median diameter is essentially a Stokes diameter and may be determined using a Joyce Loebl sedimentation disc centrifuge either in a two layer or line
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Hartley Philip S.
Stevens John
Fisons plc
Rose Shep K.
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