Multi-particulate pharmaceutical composition of quetiapine

Patent metadata

Field	Value
Publication number	US-11690805-B2
Application number	US-202117550785-A
Country	US
Kind code	B2
Filing date	Dec 14, 2021
Priority date	Sep 21, 2020
Publication date	Jul 4, 2023
Grant date	Jul 4, 2023

Abstract

The present invention discloses an extended release multi-particulate sprinkle composition comprising a plurality of discrete units, each discrete unit comprising quetiapine or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

First claim

The invention claimed is:

1. An extended release multi-particulate sprinkle dosage form comprising a plurality of discrete units, wherein each unit comprises:
a) a drug core comprising an active pharmaceutical ingredient and pharmaceutically acceptable excipients, wherein the active pharmaceutical ingredient consists of quetiapine or a pharmaceutically acceptable salt thereof;
b) at least two coatings on the drug core and a pore former wherein a first of the at least two coatings is an extended release coating comprising a pH neutral polymer and a second of the at least two coatings comprises a pH sensitive polymer;
wherein the pore former is in the extended release coating and the ratio of PH neutral polymer and pore former in the extended release coating is 80:20 to 95:5, and
wherein the release of the drug is controlled by a combination of said at least two coatings,
wherein said dosage form with high fat meals results in not more than a 35% change in Cmax or AUC when compared to a similar dosing under fasting condition.

2. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein the second of the at least two coatings is a delayed release coating.

3. The extended release multi-particulate sprinkle dosage form according to claim 2 , wherein the extended release coating comprises a pH neutral polymer in an amount of about 50% to about 80% based on the weight of the extended release coating.

4. The extended release multi-particulate sprinkle dosage form according to claim 2 , wherein the delayed-release coating comprises a pH sensitive polymer in an amount of about 55% to about 95% based on the weight of the delayed-release coating.

5. The extended release multi-particulate sprinkle dosage form according to claim 1 wherein the drug core is devoid of any release controlling polymer.

6. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein the coating further comprises an optional non-functional coating.

7. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein said composition further comprises pharmaceutically acceptable excipients selected from a diluent, a binder, a disintegrant, a pore-former, a lubricant, a glidant, a surfactant, a sweetener, an anti-tacking agent, an opacifier, an anti-foaming agent, a coloring agent, a flavoring agent, or a mixture thereof.

8. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein the drug release from the multi-particulate dosage form is controlled with a combination of at least one pH neutral polymer in a pH neutral coating and at least one pH sensitive polymer in a pH sensitive coating.

9. The extended release multi-particulate sprinkle dosage form according claim 1 , wherein the dosage form is in the form of a sachet, pouch or capsule.

10. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein at least one of the discrete units is a form selected from a pellet, a bead, a particle, a granule or a mini-tablet.

11. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein the pH neutral polymer is a water-insoluble polymer.

12. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein the dosage form the ratio of the pH neutral polymer and the pore former is not more than 10% by weight of the extended release coating.

13. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein D50 of at least one of said discrete units is in a range of about 0.7 to 1.3 mm or particle size of the discrete units is less than about 1.6 mm.

14. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein the administration of the sprinkle dosage form under fasting conditions provides a Cmax in range of about 180 ng/mL to about 450 ng/mL and/or a mean AUC 0-inf in the range of 4000 hr.ng/mL to 4800 hr.ng/mL.

15. The extended release multi-particulate sprinkle dosage form according to claim 1 , wherein the administration of the sprinkle dosage form under fed conditions provides a Cmax in range of about 250 ng/mL to about 650 ng/mL and/or a mean AUC 0-inf in the range of 4300 hr.ng/mL to 6300 hr.ng/mL.

16. The extended release multi-particulate sprinkle dosage form according to claim 1 wherein, a higher amount of quetiapine in a dose range of 50-400 mg can be administered as a sprinkle dosage form for nasogastric administration, wherein the dosage form can be administered to a patient suffering from a psychiatric disorder selected from schizophrenia, bipolar disorder, mania, depression where patients are unconscious or having swallowing difficulty.

17. A method for treating a patient suffering from a psychotic disorders selected from schizophrenia, bipolar disorder, mania, or depression, or as an adjunctive therapy with an antidepressant, by administering a therapeutically effective amount of a multi-particulate quetiapine sprinkle dosage form according to claim 1 .

18. An extended release multi-particulate sprinkle dosage form prepared by a process comprising:
mixing quetiapine or its pharmaceutically acceptable salt with suitable excipients and at least two coatings on a drug core wherein one of the at least two coatings comprises a pH sensitive polymer; and
wherein the release of the drug is controlled by a combination of the at least two coatings.

19. The method of claim 18 , wherein said process comprises:
i. mixing quetiapine or a pharmaceutical acceptable salt thereof with suitable pharmaceutical acceptable excipients in a dry mix followed by granulation using a suitable technique;
ii. extruding the resultant from step i above followed by spheronization;
iii. drying the resulting drug containing spheroids;
iv. sifting the resultant from step iii above;
v. coating the drug containing core with suitable coatings; and
vi. lubricating the coated core followed by filling into a suitable sachet or pouch or capsule.

20. The method of claim 18 ,
wherein said excipient is selected from a diluent, a binder, a disintegrant, a pore-former, a plasticizer, a lubricant, a glidant, a surfactant, a sweetener, an anti-tacking agent, an opacifier, an anti-foaming agent, a coloring agent, a flavoring agent or a mixture thereof.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Kumar Amit
• Agarwal Ravindra
• Metia Pulak Kumar
• Ramaraju Kalaiselvan
• Madan Sumit
• Singh Romi Barat

Classifications

• A61K47/38

  Cellulose; Derivatives thereof · CPC title

• A61K9/1682

  Processes · CPC title

• A61K31/554

  having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61K9/1676 Primary

  having a drug-free core with discrete complete coating layer containing drug (adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921) · CPC title