PRECOMPACTED FAST-DISINTEGRATING FORMULATIONS OF COMPOUNDS WITH A LOW ORAL BIOAVAILABILITY

1 . A solid pharmaceutical formulation for oral administration, comprising an active pharmaceutical ingredient, a hydroswelling polymer, and a precompacted granulate of a swellable excipient.

2 . A pharmaceutical formulation as claimed in claim 1 , wherein said precompacted granulate is made by applying a compression force to the swellable excipient .

3 . A pharmaceutical formulation as claimed in claim 2 , wherein said compression force is evoked by an apparatus chosen from rollers under friction, roller or cube presses, extruders, ring matrix presses, and pelletizing presses.

4 . A pharmaceutical formulation as claimed in claim 1 , wherein said active pharmaceutical ingredient is in the form of nanoparticles.

5 . A pharmaceutical formulation according to any one of the claims 1 - 4 , further comprising permeation enhancing excipients.

6 . A pharmaceutical formulation according to any one of the claims 1 - 4 , further comprising a surfactant.

7 . A pharmaceutical formulation according to any one of the claims 1 - 6 , wherein said swellable excipient is ‘polyvinyl polypyrrolidone cross linked’.

8 . A pharmaceutical formulation according to any one of the claims 1 - 6 , wherein said hydroswelling polymer is chosen from the hydroxypropyl methylcelluloses HPMC E5 and HPMC E6, microcrystalline cellulose and polyvinyl pyrrolidone K12.

9 . A pharmaceutical formulation according to claim 6 , wherein said surfactant is chosen from sodium dodecyl sulphate and ‘vitamine E TPGS 1000’

10 . Process to prepare a formulation according to claim 1 , comprising the steps of:

(i a ) preparing a solution of a hydroswelling polymer by heating water, and thereafter adding the hydroswelling polymer while stirring, until a homogeneous suspension is obtained, which is allowed to cool,

(i b ) dissolving an active pharmaceutical ingredient and a weak acid into a surfactant, by stirring and heating,

(i c ) mixing the solution resulting from step (i a ) with that resulting from step (i b ), and spray drying the mixture,

or,

(i d ) dissolving an active pharmaceutical ingredient and a hydroswelling polymer in a solvent, and removing the solvent by evaporation, to give an amorphous dispersion,

(ii) compressing a swellable excipient (disintegrant) to a tablet,

(iii) braking the large tablet into granules ,

(iv) mixing a sieve fraction of these granules with the spray-dried product of step (i c ), or the amorphous dispersion obtained in step (i d )

(v) pressing a tablet of the obtained mixture.

11 . Process according to claim 10 , wherein said swellable excipient is ‘polyvinyl polypyrrolidone cross linked’.

12 . Process according to claim 10 , wherein said hydroswelling polymer is chosen from the hydroxypropyl methylcelluloses HPMC E5 and HPMC E6, microcrystalline cellulose and polyvinyl pyrrolidone K12

13 . Process according to claim 10 , wherein said surfactant is chosen from sodium dodecyl sulphate and ‘vitamine E TPGS 1000’

14 . Process according to claim 10 , wherein said weak acid is citric.