Ribociclib tablet

• US 10,799,506 B2
• Filed: 04/14/2016
• Issued: 10/13/2020
• Est. Priority Date: 04/16/2015
• Status: Active Grant

• Current Assignee: Novartis Pharmaceuticals Corporation (Novartis Ag)
• Original Assignee: Novartis Ag
• Inventors: Gururajan, Bindhumadhavan, Grandeury, Arnaud, Costa, Rui
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US15/564,534
• Publication Number:
  US 20180071292A1
• Time in Patent Office: 1,643 Days
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present disclosure is directed to oral tablet of ribociclib including its salt(s). One embodiment of the present disclosure is directed to tablet of ribociclib with high drug load with an immediate release profile. One embodiment of the present disclosure is directed to coated tablet of ribociclib. Another embodiment of the present disclosure is directed to coated tablet of ribociclib where the coating is an advanced moisture barrier coating (e.g., Opadry® amb II coating where the coating is PVA based).

Claims

1. A coated pharmaceutical oral tablet comprising tablet core and a coating, wherein the tablet core comprises at least 40% of ribociclib succinate (w/w), the coating comprises 45.52% polyvinyl alcohol (PVA), 20% talc, 2% lecithin, and 0.48% xanthan gum, and lacks hydroxypropyl methylcellulose (HPMC), and the tablet releases at least 75% of the ribociclib or its salt after 45 minutes when tested with the rotating basket at 100 rpm with 900 ml of dissolution media pH 2 or pH 4.5, at 37°

C., according to United States Pharmacopeia (USP)<

711>

.

2. The tablet of claim 1 wherein the % of ribociclib succinate (w/w) is at least 50% of the tablet core.

3. The tablet of claim 2 wherein the % of ribociclib succinate (w/w) is at least 55% of the tablet core.

4. The tablet of claim 3, wherein the % of ribociclib succinate (w/w) is at about 55% to 65% of the tablet core.

5. The tablet of claim 1 wherein the % of ribociclib (w/w) is at about 60% of the tablet core.

6. The coated tablet according to claim 1, wherein the coating comprises 32% iron oxide.

7. A coated tablet comprising a tablet core and a coating, wherein the tablet core comprises:

(a) an inner phase comprising;

(i) ribociclib succinate;

(ii) microcrystalline cellulose;

(iii) hydroxypropylcellulose;

(iv) crospovidone;

(v) colloidal silicon dioxide; and

(vi) magnesium stearate; and

(b) an outer phase comprising;

(i) crospovidone;

(ii) colloidal silicon dioxide;

(iii) magnesium stearate; and

wherein the ribociclib succinate is present in an amount of at least 40% by weight of the tablet core and wherein the coating comprises 45.52% polyvinyl alcohol (PVA), 20% talc, 2% lecithin, and 0.48% xanthan gum, and lacks hydroxypropyl methylcellulose (HPMC).

8. The coated tablet according to claim 7, wherein

(a) the inner phase comprises:

(i) 63.600 mg ribociclib succinate;

(ii) 16.860 mg microcrystalline cellulose;

(iii) 12.030 mg hydroxypropylcellulose;

(iv) 7.300 mg crospovidone;

(v) 0.530 mg colloidal silicon dioxide; and

(vi) 1.590 mg magnesium stearate; and

(b) the outer phase comprises;

(i) 3.210 mg crospovidone;

(ii) 0.265 mg colloidal silicon dioxide; and

(iii) 2.115 mg magnesium stearate.

9. The coated tablet according to claim 7, wherein

(a) the inner phase comprises:

(i) 254.40 mg ribociclib succinate;

(ii) 67.44 mg microcrystalline cellulose;

(iii) 48.12 mg hydroxypropylcellulose;

(iv) 29.20 mg crospovidone;

(v) 2.12 mg colloidal silicon dioxide; and

(vi) 6.36 mg magnesium stearate; and

(b) the outer phase comprises;

(i) 12.84 mg crospovidone;

(ii) 1.06 mg colloidal silicon dioxide; and

(iii) 8.46 mg magnesium stearate.

10. The coated tablet according to claim 7, wherein

(a) the inner phase comprises:

(i) 127.2 mg ribociclib succinate;

(ii) 33.72 mg microcrystalline cellulose;

(iii) 24.06 mg hydroxypropylcellulose;

(iv) 14.60 mg crospovidone;

(v) 1.06 mg colloidal silicon dioxide; and

(vi) 3.18 mg magnesium stearate; and

(b) the outer phase comprises;

(i) 6.420 mg crospovidone;

(ii) 0.53 mg colloidal silicon dioxide; and

(iii) 4.23 mg magnesium stearate.

11. The coated tablet according to claim 7, wherein

(a) the inner phase comprises:

(i) 190.8 mg ribociclib succinate;

(ii) 50.58 mg microcrystalline cellulose;

(iii) 36.09 mg hydroxypropylcellulose;

(iv) 21.9 mg crospovidone;

(v) 1.59 mg colloidal silicon dioxide; and

(vi) 4.77 mg magnesium stearate; and

(b) the outer phase comprises;

(i) 9.63 mg crospovidone;

(ii) 0.795 mg colloidal silicon dioxide; and

(iii) 6.345 mg magnesium stearate.

12. The coated tablet according to claim 7, wherein

(a) the inner phase comprises:

(i) 381.6 mg ribociclib succinate;

(ii) 101.16 mg microcrystalline cellulose;

(iii) 72.18 mg hydroxypropylcellulose;

(iv) 43.8 mg crospovidone;

(v) 3.18 mg colloidal silicon dioxide; and

(vi) 9.54 mg magnesium stearate; and

(b) the outer phase comprises;

(i) 19.26 mg crospovidone;

(ii) 1.59 mg colloidal silicon dioxide; and

(iii) 12.69 mg magnesium stearate.

13. The coated tablet according to claim 7, wherein the coating comprises 32% iron oxide.

14. The coated tablet according to claim 7, wherein the tablet releases at least 75% of the ribociclib or its salt after 45 minutes when tested with the rotating basket at 100 rpm with 900 ml of dissolution media pH 2 or pH 4.5, at 37°

C., according to United States Pharmacopeia (USP)<

711 >

.