Dosage form comprising succinimide drug for treating depressive disorders and composition comprising same

• US 5,185,158 A
• Filed: 02/27/1992
• Issued: 02/09/1993
• Est. Priority Date: 02/27/1992
• Status: Expired due to Term

• Current Assignee: Encinal Pharmaceutical Investments, LLC
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Ayer, Atul, Ridzon, Dana
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US07/842,682
• Time in Patent Office: 348 Days
• Field of Search: 424/473, 424/471, 514/253, 514/772.4
• US Class Current: 424/473
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

A dosage form is provided for administering a drug of the formula ##STR1## to a patient to produce an anxiolytic benefit in the patient.

Claims

1. A therapeutic composition of matter comprising a drug of the following formula:

##STR7## and a polymer comprising the repeating molecular unit, --(--O--CH₂ CH₂ --)--_n, wherein n is 4500 to 5000, which therapeutic composition is useful for administering the drug to a patient in need of the drug for treating depressive disorders, and for antidepressive and anxiolytic therapy.

2. A therapeutic composition of matter comprising a drug of the following formula, ##STR8## and a pharmaceutically acceptable polymer comprising the repeating molecular unit, --(--O--CH₂ CH₂ --)--_n, wherein n is 6500 to 7500, which therapeutic composition is useful for administering the drug to a patient in need of the drug for treating depressive disorders, and for antidepressive and anxiolytic therapy.

3. An improvement in a dosage form for delivering a drug to a human, wherein the dosage form comprises:

(a) a wall comprising a composition permeable to the passage of fluid, which wall surrounds;

(b) a compartment;

(c) at least one exit in the wall that connects the exterior of the dosage form with the compartment;

(d) a push composition in the compartment comprising an osmopolymer that, in the presence of fluid in the compartment, expands and occupies space in the compartment;

(e) a drug composition in the compartment comprising the drug of the following formula;

##STR9## wherein A is a member selected from the group consisting of oxygen, methylene, and ethylene;

( ) is a member selected from the group consisting of a single bond and a double bond;

R is a member selected from the group consisting of phenyl, phenyl substituted with a halogen, a C₁ to C₄ alkoxy, a trifluoromethyl, a 2-pyridyl, and a 2-pyrimidinyl group; and

n is 3 to 4; and

wherein the improvement comprises formulating the drug with a first polymer comprising a repeating molecular unit --(--O--CH₂ CH₂ --)--_n, wherein n is 4500 to 5000, and with a second polymer comprising a repeating molecular unit --(--O--CH₂ CH₂ --)--_n, wherein n is 6500 to 7500, which first and second polymer carry the drug from the dosage form and release the drug essentially-free of polymer retention.

4. An improvement in an dosage form for delivering the drug according to claim 3, wherein the drug in the compartment is present as a pharmaceutically acceptable salt.

5. An improvement in a dosage form for delivering the drug according to claim 3, wherein the drug in the compartment is 4,7-methano-1H-isoindole-1,3(2H)-dione, hexahydro-2-[4-[-(2-pyrimidinyl)-1-piperzinyl]butyl]-(3aα

,4β

,7aα

)-2-hydroxy-1,2,3-propanetricarboxylate(1;

1).

6. An improvement in a dosage form for delivering the drug according to claim 3, wherein the drug is a member selected from the group consisting of the exo and endo forms of the drug.

7. An osmotic dosage form for administering tandospirone to a patient in need of tandospirone therapy, wherein the dosage form comprises:

(a) a wall comprising a member selected from the group consisting of cellulose acylate, cellulose diacylate and cellulose triacylate, which wall surrounds;

(b) an internal compartment;

(c) at least one exit passageway in the wall that connects the exterior of the dosage form with the compartment;

(d) a push composition in the compartment comprising an osmopolymer that, in the presence of fluid that enters the compartment increases in dimensions and thereby occupies space in the compartment; and

wherein the osmotic dosage form is characterized by;

(e) a drug composition comprising 1 mg to 750 mg of tandospirone, a poly(ethylene oxide) comprising a molecular weight of 2>

10⁵, and a poly(ethylene oxide) comprising molecular weight of 3×

10⁵, which composition delivers the tandospirone from the dosage form to the patient at a substantially zero order rate of release over a period of 24 hours.

8. An osmotic dosage form for administering tandospirone to a patient according to claim 7, wherein the tandospirone comprises a member selected from the group consisting of endo tandospirone and exo tandospirone.

9. A process for producing anxiolytic therapy in a patient in need of this therapy, wherein the process comprises administering a composition comprising (a) 1 mg to 750 mg of tandospirone and a nontoxic polymer selected from the group consisting of (b) a polymer comprising a repeating --(--O--CH₂ CH₂ --)-- unit and a 200,000 molecular weight and (c) a polymer comprising a repeating --(--O--CH₂ CH₂ --)-- unit and a 300,000 molecular weight, to the patient to produce the anxiolytic therapy.