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“Novel Crystalline Forms Of Ribociclib Succinate”

Abstract: The present invention relates to the process for preparing crystalline forms of Ribociclib succinate (1).

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Patent Information

Application #
Filing Date
06 September 2018
Publication Number
11/2020
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
radha@biophore.com
Parent Application

Applicants

Biophore India pharmaceuticals Pvt. Ltd
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Inventors

1. Manik Reddy Pullagurla
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
2. Bhaskar Reddy Pitta
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
3. Rajesham Boge
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
4. Jagadeesh Babu Rangisetty
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Specification

We claim:
1. A process for the preparation of crystalline forms BP-1, BP-1, BP-2, BP-3, BP-4, BP-5 of Ribociclib succinate (1) comprising:
a) Providing Ribociclib succinate (1) in a suitable protic or aprotic solvent or mixtures thereof at 25-30 °C;
b) optionally, heating the reaction mixture at 50-70 °C;
c) optionally, cooling the filtrate to -20 to 35 °C;
d) isolating crystalline forms of Ribociclib succinate (1); and
e) drying the isolated product under suitable conditions.
2. The process of claim 1, wherein the solvent is selected from a group comprising of water, methanol, ethanol, isopropyl alcohol, benzyl alcohol, butyl alcohol, isobutyl alcohol, acetone, acetonitrile, 1,4-dioxane, diethyl ether, dichloromethane, ethyl acetate, n-butyl acetate , N,N-dimethylformamide, methyl tertiary butyl ether, diethyl ether, n-hexane, cyclohexane, toulene, tetrahydrofuran or mixtures thereof.
3. A process for the preparation of crystalline forms BP-6 of Ribociclib succinate (1) comprising of the following steps:
a) Providing Ribociclib free base in a suitable first solvent at 25-30 °C;
b) providing succinic acid in a suitable second solvent at 25-30 °C;
c) heating the reaction mass to a suitable temperature;
d) cooling and filtering the reaction mass;
e) adding the Ribociclib free base solution and succinic acid solution to a suitable third solvent at 25-35°C; and
f) isolating crystalline form BP-6 of Ribociclib succinate (1) using a suitable technique.

4. The process of claim 3, wherein the solvent is selected from a group comprising of water, methanol, ethanol, isopropyl alcohol, benzyl alcohol, butyl alcohol, isobutyl alcohol, acetone, acetonitrile, 1,4-dioxane, diethyl ether, dichloromethane, ethyl acetate, n-butyl acetate , N,N-dimethylformamide, methyl tertiary butyl ether, diethyl ether, n-hexane, cyclohexane, n-heptane, toulene, tetrahydrofuran or mixtures thereof.
5. The process of claim 3, wherein the suitable technique used for isolation of crystalline form is selected from a group comprising of vacuum filtration, centrifugal filtration, gravity filtration, cold filtration, hot filtration, vacuum nutsehe filtration, pressure nutsche filtration.
6. A process for the preparation of crystalline forms BP-7 of Ribociclib succinate (1) comprising:
a) Providing Ribociclib free base in a suitable first solvent at 25-30 °C;
b) heating the reaction mass to a suitable temperature;
c) adding the second solvent to the Ribociclib free base solution at a suitable temperature;
d) adding succinic acid to the reaction solution at a suitable temperature;
e) cooling and filtering the reaction mass; and
f) isolating crystalline form BP-7 of Ribociclib succinate (1) using a suitable technique.
7. The process of claim 6, wherein the suitable solvent is selected from a group comprising of water, methanol, ethanol, isopropyl alcohol, benzyl alcohol , acetone, acetonitrile, nitromethane, 1,4-dioxane, diethyl ether, dichloromethane, 1,4-dioxane, ethyl acetate, n-butyl acetate, N, N-dimethylformamide, methyl tertiary butyl ether, hexane, cyclohexane, toulene, n-heptane, tetrahydrofuran or mixtures thereof.

8. The process of claim 6, wherein the suitable technique used for isolation of crystalline form is selected from a group comprising of air tray dryer, vacuum tray dryer, fluidized bed dryer, spin flash dryer, flash dryer and spray dryer.

Documents

Application Documents

# Name Date
1 201841033501-PROVISIONAL SPECIFICATION [06-09-2018(online)].pdf 2018-09-06
2 201841033501-FORM 1 [06-09-2018(online)].pdf 2018-09-06
3 201841033501-DRAWINGS [06-09-2018(online)].pdf 2018-09-06
4 abstract_201841033501 .jpg 2018-09-10
5 Form1_Proof of Right_20-09-2018.pdf 2018-09-20
6 Correspondence by Applicant_Form1_20-09-2018.pdf 2018-09-20
7 201841033501-FORM 3 [29-08-2019(online)].pdf 2019-08-29
8 201841033501-ENDORSEMENT BY INVENTORS [29-08-2019(online)].pdf 2019-08-29
9 201841033501-COMPLETE SPECIFICATION [29-08-2019(online)].pdf 2019-08-29
10 Correspondence by Agent_Form-2, complete, Form-3 And Form-5_03-09-2019.pdf 2019-09-03