Methods and dosage forms for controlled delivery of paliperidone and risperidone

• US 9,393,192 B2
• Filed: 04/22/2009
• Issued: 07/19/2016
• Est. Priority Date: 07/29/2002
• Status: Active Grant

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Yam, Nyomi V., Reyes, Iran, Davar, Nipun, Ayer, Atul D., Lee, Julie, Seroff, Sonya, Gupta, Suneel K., Sathyan, Gayatri
• Primary Examiner(s): Soroush, Ali
• Application Number:
  US12/428,422
• Publication Number:
  US 20090202631A1
• Time in Patent Office: 2,645 Days
• Field of Search: 424/464, 424/468, 424/474, 544/282
• US Class Current: 1/1
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer

Abstract

Dosage forms and methods for providing a substantially ascending rate of release of paliperidone or risperidone are provided. The sustained release dosage forms provide therapeutically effective average steady-state plasma paliperidone or risperidone concentrations when administered once per day. This once-a-day dosing regimen results in only one peak plasma paliperidone or risperidone concentration occurrence in each 24 hour period. In addition, the peak plasma paliperidone or risperidone concentration occurs at a later time following dose administration and exhibits a lesser magnitude than the peak plasma paliperidone or risperidone concentration that occurs following administration of paliperidone or risperidone in an immediate-release dosage form.

Claims

1. A method for treating a subject in need of treatment comprising orally administering a once-a-day oral dosage form containing as an active agent a therapeutically effective amount of paliperidone or a pharmaceutically acceptable addition salts thereof wherein the dosage form comprises:

(a) a core having three layers and a portion of the active agent is contained within a first drug composition layer and the remaining portion of the active agent is contained within a second drug composition layer, wherein the proportion of active agent contained within the first layer to the active agent contained within the second layer is less than about 0.33, wherein the first drug composition layer contains an osmagent and a second drug composition layer does not contain an osmagent and wherein a fluid-expandable polymer is contained within a third layer;

(b) a subcoat surrounding said core;

(c) a semipermeable membrane surrounding the core to form a compartment having an osmotic gradient to drive fluid from an external fluid environment contacting the semipermeable membrane into the compartment; and

(d) an orifice formed through the semipermeable membrane and into the core to permit the active agent to be released from within the compartment into the external fluid environment wherein the first drug composition layer is proximal to the orifice;

wherein the dosage form following oral administration to said subject releases the active agent at a substantially ascending release rate for at least 18 hours as determined by in vitro dissolution testing.

2. The method of claim 1 for administering an active agent to a subject wherein the core is a capsule shaped tablet.

3. The method according to claim 1 wherein the osmagent is sodium chloride salt.

4. The method according to claim 1 wherein a C_maxoccurs after about 14 hours after administration to the subject.

5. The method according to claim 1 wherein a C_maxoccurs between about 16 hours and about 22 hours after administration to the subject.

6. The method according to claim 1 wherein a C_maxoccurs between about 18 hours and about 21 hours after administration to the subject.

7. The method according to claim 1 wherein the concentration of active agent in the first drug layer to the concentration of active agent in the second drug layer is less than 0.44.

13. The method according to claim 1 wherein the first drug composition layer contains at least 20% an osmagent.

8. A oral tablet dosage form comprising as an active agent a therapeutically effective amount of paliperidone or a pharmaceutically acceptable addition salts thereof wherein the dosage form comprises:

(a) a core having three layers and a portion of the active agent is contained within a first drug composition layer and the remaining portion of the active agent is contained within a second drug composition layer, wherein the proportion of active agent contained within the first layer to the active agent contained within the second layer is less than about 0.33, wherein the first drug composition layer contains an osmagent and a second drug composition layer does not contain an osmagent and wherein a fluid-expandable polymer is contained within a third layer;

(b) a subcoat surrounding said core;

(c) a semipermeable membrane surrounding the core to form a compartment having an osmotic gradient to drive fluid from an external fluid environment contacting the semipermeable membrane into the compartment; and

(d) an orifice formed through the semipermeable membrane and into the core to permit the active agent to be released from within the compartment into the external fluid environment wherein the first drug composition layer is proximal to the orifice;

wherein the dosage form following oral administration to a subject releases the active agent from the dosage form at a substantially ascending release rate for at least 18 hours as determined by in vitro dissolution testing.

9. The dosage form of claim 8 characterized by releasing the active agent from the dosage form at a substantially ascending rate of release for about 18 hours to about 20 hours.

10. The dosage form of claim 8 characterized by having a T₉₀ from the core occurring at about 20 hours.

11. The dosage form according to claim 8 further comprising a subcoat for reducing the rate of degradation of the active agent paliperidone, which subcoat comprises a hydroxyalkylcellulose polymer possessing a 8,500 to 4,000,000 molecular weight that at least partially surrounds the core and is positioned between an inside surface of the semipermeable membrane and the core.

12. The dosage form according to claim 8 further comprising a subcoat for reducing the rate of degradation of the active agent pafiperidone which subcoat comprises a mixture of hydroxypropyl cellulose and providone prepared in ethanol that at least partially surrounds the core and is positioned between an inside surface of the semipermeable membrane and the core.

14. The dosage form according to claim 8 wherein the first drug composition layer contains at least 20% an osmagent.