DARUNAVIR FORMULATIONS
This invention relates to solid oral dosage forms of the HIV inhibitor darunavir and/or a pharmaceutically acceptable salt or solvate thereof, and combination formulations thereof.
1 . A darunavir granulate composition consisting of darunavir or a pharmaceutically acceptable salt or solvate thereof, Hypromellose and any residual water from the granulation.
2 . A darunavir granulate composition according to claim 1 , wherein the darunavir is present in the form of its ethanolate and the Hypromellose is Hypromellose 2910 15 mPa·s.
3 . An oral dosage form comprising about 0.4 to 0.6% by weight (w/w) of a lubricant, about 2 to 4% by weight (w/w) of a disintegrant, microcrystalline cellulose, and about 50 to 90% by weight (w/w) of a darunavir granulate according to claim 1 or 2 , the core being optionally coated with a film coating.
4 . An oral dosage form according to claim 3 , wherein the at least part of the microcrystalline cellulose is Ceolus KG802.
5 . An oral dosage form according to claim 3 or 4 , wherein said core further comprises an additional active ingredient.
6 . An oral dosage form according to claim 5 , wherein the additional active ingredient is a cytochrome P450 inhibitor.
7 . An oral dosage form according to any one of the preceding claims comprising about 0.5% by weight (w/w) of a lubricant
8 . An oral dosage form according to any one of the preceding claims, wherein the desintegrant is polyplasdone XL-10 and the lubricant is magnesium stearate
9 . An oral dosage form according to any one of the preceding claims, comprising about 800 mg free form equivalent of darunavir.
10 . A process for preparing an oral dosage form as claimed in any of the preceding claims which comprises the steps of:
Providing granulated darunavir by; mixing water and Hypromellose 2910 15 mPa·s, spraying this first mixture on a powder of darunavir or a pharmaceutically acceptable salt or solvate thereof, and drying the so obtained darunavir granulate
Providing a second mixture comprising microcrystalline cellulose, and a disintegrant,
Adding granulated darunavir to the mixture and subsequent dry-blending
Adding a lubricant and mixing until homogeneous,
Compressing the mixture to provide the oral dosage form, said oral dosage form then being optionally film-coated.
11 . An oral dosage form as claimed in any of claims 1 to 9 for use in medicine.
12 . An oral dosage form as claimed in any of claims 1 to 9 for use in the treatment of HIV infection.
13 . A method for the treatment of an HIV infection in a subject which comprises administering to the subject an effective amount of an oral dosage form as claimed in any of claims 1 to 9 .