Solid pharmaceutical formulations comprising BIBW 2992

Abstract

The present invention relates to a pharmaceutical dosage form containing the active substance BIBW 2992 as the dimaleate salt, providing an immediate release profile of the active substance, further, the invention relates to compacted intermediates comprising BIBW 2992 dimaleate salt (BIBW 2992 MA2) in form of a powder prepared using a combined roller compaction and sieving step from BIBW 2992 MA2, intermediate blends prepared from said compacted intermediate as well as solid oral formulations providing an immediate release profile of the active substance, made from said compacted intermediate or from said intermediate blends ready for use / ingestion, e.g. capsule and tablet formulations such as uncoated or film-coated tablets prepared by direct-compression, and methods for their production.

Description

technical field [0001] The present invention relates in one aspect to a pharmaceutical dosage form comprising the active substance BIBW 2992 dimaleate, which provides an immediate release dissolution profile of the drug product. [0002] According to a second aspect, the present invention relates to compacted intermediates in powder form comprising precipitated BIBW 2992 dimaleate (hereinafter abbreviated as BIBW 2992MA 2 ), the compacted intermediate can be passed through a combination of compaction steps (roller compaction (roller compaction), briquetting (briquetting) or pre-pressing (slugging)) followed by one or more sieving steps, from BIBW2992MA 2 , optionally mixed with a lubricant such as magnesium stearate; intermediate blends prepared from the compacted intermediate; and ready-to-use / edible solids providing immediate release dissolution properties Oral formulations, made from said compacted intermediates or from blends of said intermediates, such as oral powders or...

AI Technical Summary

Problems solved by technology

In conclusion, the uniformity of API content in batches is not enough

Furthermore, the disintegration and hardness of the tablets obtained from the dry granule API are unsatisfactory due to the double compaction of the mixture

[0054] Whereas experiments with milled API using dry granulation resulted in stable granules with excellent content consistency and a product free of needles in the final blend, all due to the increased surface area of ​​the soluble API. The disintegration of the obtained tablets is unsatisfactorily prolonged

[0055] Another disadvantage is that the granules contain a large amount of fine powder, which leads to changes in the compression force

[0056] Hot melt granulation with precipitated API also yields stable granules with excellent content uniformity and a product free of needle-like crystals in the final blend, however, the disadvantage of this method is that it requires Changes in compression force, changes in product bulk density and the tendency to form wall-adhesion in the granulation barrel of the mixer

[0057] The results outlined above show that, in fact, for BIBW 2992MA 2 Simple routine application of state-of-the-art techniques is not possible to ensure a stable process with constant drug quality in terms of varying physicochemical characteristics

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