| 摘要 |
Disclosed is a process for the preparation of a solid pharmaceutical composition comprising 0.5 mg to 10 mg of a DPP IV inhibitor active ingredient or a salt thereof, a first diluent, a second diluent, a binder, a disintegrant and a lubricant; said process comprising: a) dissolving a binder in a solvent to produce a granulation liquid; b) blending a DPP-IV inhibitor, a first and second diluent, and a disintegrant to produce a pre-mix; c) moistening the pre-mix with the granulation liquid and subsequently granulating the moistened pre-mix; d) optionally sieving the granulated pre-mix through a sieve with a mesh size of at least 1.0 mm; e) drying the granulate at about 40-75°C until the desired loss on drying value in the range of 1-5 % is obtained; f) delumping the dried granulate; and g) adding lubricant to the granulate for final blending; wherein the diluents are selected from cellulose powder, dibasic calciumphosphate anhydrous, dibasic calciumphosphate dihydrate, erythritol, low substituted hydroxypropyl cellulose, mannitol, pregelatinized starch and xylitol; the binder is selected from copovidone (copolymerisates of vinylpyrrolidon with other vinylderivates), hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose (HPC), polyvinylpyrrolidon (povidone), pregelatinized starch, or low-substituted hydroxypropylcellulose (L-HPC); the disintegrant is selected from corn starch, crospovidone, low-substituted hydroxypropylcellulose (L-HPC) or pregelatinized starch; and the lubricant is selected from talc, polyethyleneglycol, calcium behenate, calcium stearate, hydrogenated castor oil or magnesium stearate; and wherein the DPP IV inhibitor is selected from a compound such as 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-aminopiperidin-1-yl)-xanthine (linagliptin). |
