Modified release compositions comprising tacrolimus
AssigneeVeloxis Pharmaceuticals A/S
InventorsPer Holm, Tomas Norling
Life of this patent
Estimating the term…
Abstract
A modified release composition comprising tacrolimus releases less than 20% w/w of the active ingredient within 0.5 hours when subjected to an in vitro dissolution test using USP Paddle method and using 0.1 N HCl as dissolution medium and has increased bioavailability by effectively reducing or even avoiding the effects of CYP3A4 metabolism. The modified composition may be coated with an enteric coating; and/or may comprise a solid dispersion or a solid solution of tacrolimus in a hydrophilic or water-miscible vehicle and one or more modifying release agents; and/or may comprise a solid dispersion or a solid solution of tacrolimus in an amphiphilic or hydrophobic vehicle and optionally one or more modifying release agents.
Claims19
An oral extended release pharmaceutical composition comprising a therapeutically effective amount of tacrolimus and one or more modifying release agents wherein the composition releases at most 62% of the tacrolimus in the composition within 15 hours when subjected to an in vitro dissolution test using USP Paddle method at a rotation speed of 50 rpm in a 900mL aqueous dissolution medium with 0.005% hydroxypropylcellulose which has been adjusted to pH 4.5.
An oral extended release pharmaceutical composition comprising (a) a therapeutically effective amount of tacrolimus dispersed or dissolved in a vehicle, and (b) one or more modifying release agents, wherein
- (i) the vehicle comprises a poloxamer, and
- (ii) the composition releases at most 62% of the tacrolimus in the composition within 15 hours when subjected to an in vitro dissolution test using USP Paddle method at a rotation speed of 50 rpm in a 900mL aqueous dissolution medium with 0.005% hydroxypropylcellulose which has been adjusted to pH 4.5.
An oral extended release pharmaceutical composition comprising (a) a therapeutically effective amount of tacrolimus dispersed or dissolved in a vehicle, (b) one or more modifying release agents, and (c) a solid carrier, wherein
- (i) the vehicle comprises polyethylene glycol having a molecular weight of from about 1,000 to about 35,000 and a poloxamer, and
- (ii) the composition releases at most 62% of the tacrolimus in the composition within 15 hours when subjected to an in vitro dissolution test using USP Paddle method at a rotation speed of 50 rpm in a 900mL aqueous dissolution medium with 0.005% hydroxypropylcellulose which has been adjusted to pH 4.5.
Dependencies are inferred from the claim text.