ORALLY DISINTEGRATING TABLET COMPRISING AMORPHOUS SOLID DISPERSION OF NILOTINIB AND IN VITRO CHARACTERIZATION THEREOF
Amorphous solid dispersions and pharmaceutical compositions of the protein kinase inhibitor nilotinib. The pharmaceutical compositions may be used in methods of treating a proliferative disorder such as cancer. In particular, the present disclosure provides a pharmaceutical composition in the form of an orally disintegrating tablet. In some embodiments, the pharmaceutical compositions can be administered without regard to food consumption. In other embodiments, the pharmaceutical compositions can be administered at a significantly lower dose as compared to a commercially available immediate-release nilotinib formulation, while providing a comparable therapeutic effect. The disclosure further provides a discriminating in vitro dissolution characterization method.
1 - 30 . (canceled)
31 . A kit for sale to a user, the kit comprising a pharmaceutical composition and a package insert;
wherein the pharmaceutical composition is in the form of an orally disintegrating tablet that comprises an amorphous solid dispersion;
wherein the amorphous solid dispersion comprises nilotinib and one or more polymers;
wherein the orally disintegrating tablet comprises 10 mg to 100 mg nilotinib;
wherein the orally disintegrating tablet is characterized by a disintegration time of 40 seconds or less, as determined according to USP <701> Disintegration, using a basket-rack apparatus with disks in a medium of distilled water;
wherein the package insert informs the user that the pharmaceutical composition can be administered with food; and
wherein the package insert further indicates to the user a dosage that is at least 50% less as compared to a labeled dosage of a conventional immediate-release crystalline nilotinib formulation.
32 . The kit of claim 31 , wherein the disintegration time is 30 seconds or less.
33 . The kit of claim 31 , wherein, when the orally disintegrating tablet is subjected to dissolution testing according to USP <711> Dissolution using Apparatus 2 at 100 rpm and a dissolution medium consisting of 20 mM citrate buffer at pH 3.1, at least 10% of the nilotinib is released into the dissolution medium within 30 minutes.
34 . The kit of claim 33 , wherein in the dissolution testing at least 25% of the nilotinib is released into the dissolution medium within 30 minutes.
35 . The kit of claim 31 , wherein the orally disintegrating tablet is free from flavorants.
36 . The kit of claim 31 , wherein the orally disintegrating tablet comprises 10 to 100 mg nilotinib the package insert indicates to the user a dosage that is at least 60% less as compared to a labeled dosage of a conventional immediate-release crystalline nilotinib formulation.
37 . The kit of claim 31 , wherein the orally disintegrating tablet comprises 15 to 75 mg nilotinib.
38 . A kit for sale to a user, the kit comprising a pharmaceutical composition and a package insert;
wherein the pharmaceutical composition is in the form of an orally disintegrating tablet that comprises an amorphous solid dispersion;
wherein the amorphous solid dispersion comprises nilotinib and one or more polymers;
wherein the orally disintegrating tablet comprises 10 mg to 100 mg nilotinib;
wherein the orally disintegrating tablet is characterized by a disintegration time of 40 seconds or less, as determined according to USP <701> Disintegration, using a basket-rack apparatus with disks in a medium of distilled water;
wherein the package insert informs a user of the kit that the pharmaceutical composition can be administered with or without food; and
wherein the package insert further indicates to the user a dosage that is at least 50% less as compared to a labeled dosage of a conventional immediate-release crystalline nilotinib formulation.
39 . The kit of claim 38 , wherein the disintegration time is 30 seconds or less.
40 . The kit of claim 38 , wherein, when the orally disintegrating tablet is subjected to dissolution testing according to USP <711> Dissolution using Apparatus 2 at 100 rpm and a dissolution medium consisting of 20 mM citrate buffer at pH 3.1, at least 10% of the nilotinib is released into the dissolution medium within 30 minutes.
41 . The kit of claim 40 , wherein in the dissolution testing at least 25% of the nilotinib is released into the dissolution medium within 30 minutes.
42 . The kit of claim 38 , wherein the orally disintegrating tablet is free from flavorants.
43 . The kit of claim 38 , wherein the package insert indicates to the user a dosage that is at least 60% less as compared to a labeled dosage of a conventional immediate-release crystalline nilotinib formulation.
44 . The kit of claim 38 , wherein the orally disintegrating tablet comprises 15 to 75 mg nilotinib.
45 . A kit for sale to a user, the kit comprising a pharmaceutical composition and a package insert;
wherein the pharmaceutical composition is in the form of an orally disintegrating tablet that comprises an amorphous solid dispersion;
wherein the amorphous solid dispersion comprises nilotinib and one or more polymers;
wherein the orally disintegrating tablet comprises 10 mg to 100 mg nilotinib;
wherein the orally disintegrating tablet is characterized by a disintegration time of 40 seconds or less, as determined according to USP <701> Disintegration, using a basket-rack apparatus with disks in a medium of distilled water; and
wherein the package insert does not include a warning that the pharmaceutical composition should not be administered with food; and
wherein the package insert further indicates to the user a dosage that is at least 50% less as compared to a labeled dosage of a conventional immediate-release crystalline nilotinib formulation.
46 . The kit of claim 45 , wherein the disintegration time is 30 seconds or less.
47 . The kit of claim 45 , wherein, when the orally disintegrating tablet is subjected to dissolution testing according to USP <711> Dissolution using Apparatus 2 at 100 rpm and a dissolution medium consisting of 20 mM citrate buffer at pH 3.1, at least 10% of the nilotinib is released into the dissolution medium within 30 minutes.
48 . The kit of claim 47 , wherein in the dissolution testing at least 25% of the nilotinib is released into the dissolution medium within 30 minutes.
49 . The kit of claim 45 , wherein the orally disintegrating tablet is free from flavorants.
50 . The kit of claim 45 , wherein the package insert indicates to the user a dosage that is at least 60% less as compared to a labeled dosage of a conventional immediate-release crystalline nilotinib formulation.
51 . The kit of claim 45 , wherein the orally disintegrating tablet comprises 15 to 75 mg nilotinib.