Compositions and dosage forms for enhanced absorption of gabapentin and pregabalin

• US 20050163848A1
• Filed: 10/29/2004
• Published: 07/28/2005
• Est. Priority Date: 10/31/2003
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Wong, Patrick S.L., Yan, Dong, Guittard, George V.
• Application Number:
  US10/978,136
• Publication Number:
  US 20050163848A1
• Time in Patent Office: Days
• US Class Current: 424/473
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/295 Iron group metal compounds
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 47/541 Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 : Antianaemics

Abstract

A complex comprised of gabapentin or pregabalin and a transport moiety, such as an alkyl sulfate, is described. The complex has an enhanced absorption in the gastrointestinal tract, particularly the lower gastrointestinal tract. The complex, and compositions and dosage forms prepared using the complex, provide for absorption by the body of the drug through a period of ten to twenty-four hours, thus enabling a once-daily dosage form for gabapentin or pregabalin.

Claims

1. A substance comprised of gabapentin or pregabalin and a transport moiety, said gabapentin or pregabalin and said transport moiety forming a complex.

2. The substance of claim 1, wherein said transport moiety is an alkyl sulfate salt having between 6-12 carbon atoms.

3. The substance of claim 2, wherein said alkyl sulfate salt is a lauryl sulfate salt.

8. A dosage form comprising the substance of claim 1.

9. The dosage form of claim 8, wherein the dosage form is an osmotic dosage form.

10. The dosage form of claim 9, comprised of (i) a push layer;

(ii) drug layer comprising a gabapentin-transport moiety complex or a pregabalin-transport moiety complex;

(iii) a semipermeable wall provided around the push layer and the drug layer; and

(iv) an exit.

11. The dosage form of claim 9, comprised of (i) a semipermeable wall provided around an osmotic formulation a gabapentin-transport moiety complex or a pregabalin-transport moiety complex, an osmagent, and an osmopolymer;

and (ii) an exit.

12. The dosage form of claim 9, wherein the dosage form provides a total daily dose of between 200-3600 mg.

16. A method for administering gabapentin or pregabalin, comprising:

administering the substance of claim 1 to a patient in need thereof.

17. The method of claim 16, wherein said administering is via oral administration.

4. A composition, comprising,

a complex comprised of gabapentin or pregabalin and a transport moiety, and

a pharmaceutically acceptable vehicle,

wherein said composition has an absorption in the lower gastrointestinal tract at least 5-fold higher than gabapentin or pregabalin.

5. The composition of claim 4, wherein said transport moiety is an alkyl sulfate salt having between 6-12 carbon atoms.

6. The composition of claim 5, wherein said alkyl sulfate salt is a lauryl sulfate salt.

7. A dosage form comprising the composition of claim 4.

13. An improvement in a dosage form comprising gabapentin or pregabalin, the improvement comprising,

a dosage form comprising a complex of gabapentin or pregabalin and a transport moiety associated by a tight-ion pair bond.

14. The improved dosage form of claim 13, wherein said transport moiety is an alkyl sulfate salt having between 6-12 carbon atoms.

15. The improved dosage form of claim 14, wherein said alkyl sulfate salt is a lauryl sulfate salt.

18. A method of preparing a complex of gabapentin or pregabalin and a transport moiety, comprising

providing gabapentin or pregabalin;

providing a transport moiety;

combining the gabapentin or pregabalin and the transport moiety in the presence of a solvent having a dielectric constant less than that of water;

whereby said combining results in formation of a complex of gabapentin or pregabalin and the transport moiety.

19. The method of claim 18, wherein said combining includes (i) combining the gabapentin or pregabalin and the transport moiety in an aqueous solvent, (ii) adding said solvent having a dielectric constant less than that of water to the aqueous solvent, and (iii) recovering said complex from said solvent.

20. The method of claim 18, wherein said combining comprises contacting in a solvent having a dielectric constant at least two fold lower than the dielectric constant of water.

21. The method of claim 20, wherein said solvent is selected from the group consisting of methanol, ethanol, acetone, benzene, methylene chloride, and carbon tetrachloride.

22. A method of improving G.I. absorption of gabapentin or pregabalin, comprising

providing a complex comprised of gabapentin or pregabalin and a transport moiety;

and

administering the complex to a patient.

23. The method of claim 22, wherein the improved absorption comprises improved lower gastrointestinal absorption.

24. The method of claim 22, wherein the improved absorption comprises improved absorption in the upper gastrointestinal tract.