Oral dosage forms of cyclopropanecarboxylic acid {2-[(1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide
Provided herein are controlled release oral dosage forms of poorly soluble drugs, methods of making the dosage forms, and methods of their use for the treatment of various diseases and/or disorders.
1. An oral dosage form consisting of about 9% by weight of a compound of formula (I):
or a pharmaceutically acceptable salt thereof, about 34% by weight of mannitol, about 5% by weight of sodium croscarmellose, about 1% by weight of calcium stearate and about 51% by weight of polyvinylpyrrolidone-vinylacetate copolymer.
2. The oral dosage form of claim 1 , wherein the oral dosage form is prepared by the following process:
(i) blend the compound of formula (I) with hydroxypropyl methylcellulose or polyvinylpyrrolidone-vinylacetate copolymer;
(ii) process the blended product of (i) by hot melt extrusion at 190° C.;
(iii) mill the extruded product of (ii) using 18 mesh screen;
(iv) blend the milled extrudate of (iii) with prescreened crosscarmellose sodium and mannitol;
(v) blend the product of (iv) with prescreened calcium stearate; and
(vi) encapsulate the blended product of (v).
3. The oral dosage form of claim 2 , wherein the blending of steps (i) and (iv) is for 460 rotations each using a shaker mixer.
4. The oral dosage form of claim 2 , wherein the blending of step (v) is for 75 rotations using a shaker mixer.
5. The oral dosage form of claim 2 , wherein a semi-automatic encapsulator is used in step (vi).