Formulations for coated microprojections containing non-volatile counterions

• US 7,579,013 B2
• Filed: 06/29/2004
• Issued: 08/25/2009
• Est. Priority Date: 06/30/2003
• Status: Active Grant

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Cormier, Michel J. N., Maa, Yuh-Fun, Ameri, Mahmoud, Lin, WeiQi
• Primary Examiner(s): Desai; Anand U
• Application Number:
  US10/880,702
• Publication Number:
  US 20040265354A1
• Time in Patent Office: 1,883 Days
• Field of Search: None
• US Class Current: 424/400
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides for a formulation for coating one or more microprojections which reduces or minimizes the loss of counterions from the coating in order to achieve a pH-stabilized formulation.

Claims

1. A composition comprising a formulation of a pharmaceutically active agent, a volatile counterion and a non-volatile counterion, wherein said pharmaceutically active agent is hPTH(1-34) present as uncharged species and as charged species and wherein said non-volatile counterion is present in an amount sufficient to achieve a molar ratio between said uncharged species and charged species of about 1 uncharged species to at least 100 charged species;

wherein said formulation has increased pH stability and solubility when dried, and wherein said composition is applied to a transdermal delivery device having stratum corneum-piercing microprojections;

wherein said composition achieves an increase in delivery of the pharmaceutically active agent compared to a composition comprising a formulation without said non-volatile counterion.

2. The composition of claim 1, wherein said formulation has a pH, said pharmaceutically active agent has a positive charge at said formulation pH and said non-volatile counterion comprises a strong acid.

3. The composition of claim 2, wherein said strong acid has at least one pKa lower than about 2.

4. The composition of claim 3, wherein said strong acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, nitric acid, sulfonic acid, sulfuric acid, maleic acid, phosphoric acid, benzene sulfonic acid and methane sulfonic acid.

5. The composition of claim 1, wherein said pharmaceutically active agent has a mole ratio between uncharged species and charged species of at least 1 to 100 at a pH between 4 and 10.

6. The composition of claim 1, wherein said composition achieves a five fold increase in delivery of the pharmaceutically active agent compared to a composition comprising a formulation without said non-volatile counterion.

8. The composition of claim 1, wherein the non-volatile counterion comprises a weak acid or a strong acid.

9. The composition of claim 8, wherein the weak acid is glycolic acid or tartaric acid.

10. The composition of claim 8, wherein the strong acid is hydrochloric acid.

11. The composition of claim 8, wherein hPTH(1-34) is present as an acetate salt.

7. A composition comprising a formulation of a pharmaceutically active agent, a volatile counterion and a non-volatile counterion, wherein said pharmaceutically active agent is hPTH (1-34) present as uncharged species and as charged species;

wherein said pharmaceutically active agent has a positive charge at the pH of the formulation and said non-volatile counterion comprises a strong acid; and

wherein said formulation has increased pH stability and solubility when dried.

12. A composition comprising a formulation of hPTH(1-34), a volatile counterion and a non-volatile counterion from a weak or strong acid, wherein said non-volatile counterion is present in an amount sufficient to achieve a molar ratio of about 1 uncharged hPTH species to at least about 100 charged hPTH species, wherein said composition achieves an increase in delivery of said hPTH when applied to a transdermal delivery device having stratum corneum-piercing microprojections compared to a composition comprising a formulation without said non-volatile counterion.

13. The composition of claim 12, wherein the weak acid is glycolic acid or tartaric acid.

14. The composition of claim 12, wherein the strong acid is hydrochloric acid.

15. The composition of claim 12, wherein hPTH(1-34) is present as an acetate salt.