Formulations for amylin agonist peptides

Abstract

The present invention is concerned with a pharmaceutical formulation comprising an amylin agonist and optionally a buffer, a tonicifier or stabilizer, and a preservative in a container, for example, a vial, prefilled cartridge, prefilled syringe or disposable pen. This formulation may be in liquid, gel, solid or powdered form for delivery, for example, via nasal, pulmonary, oral, sublingual, buccal, transdermal, or parenteral routes. Formulation with biocompatible polymers and release modifiers, such as sugars, can facilitate controlled release after injection, minimizing the number of administrations to a patient. These formulations maintain stability upon storage under refrigerated or room temperature conditions. Such formulations can be further combined with insulin for administration to a patient.

1 . A liquid pharmaceutical formulation comprising about 0.5 to 1.0% (w/v) of an amylin agonist, a pharmaceutically acceptable excipient, and about 0.005% to 1.0% (w/v) of a preservative. 
   
   
       2 . The liquid pharmaceutical formulation according to  claim 1 , wherein said amylin agonist is pramlintide. 
   
   
       3 . The liquid pharmaceutical formulation according to  claim 1 , further comprising insulin. 
   
   
       4 . The liquid pharmaceutical formulation according to  claim 3 , wherein said insulin is glargine. 
   
   
       5 . The liquid pharmaceutical formulation according to  claim 1  wherein said preservative is selected from the group consisting of m-cresol, benzyl alcohol, ethyl, ethyl, propyl and butyl parabens and phenol. 
   
   
       6 . The liquid pharmaceutical formulation according to  claim 1 , wherein said preservative is between about 0.1 to 0.3% (w/v) of m-cresol. 
   
   
       7 . The liquid pharmaceutical formulation according to  claim 1 , wherein said preservative is at least 0.15% (w/v) of m-cresol. 
   
   
       8 . The liquid pharmaceutical formulation according to  claim 1 , wherein said amylin agonist is stable for at least 30 days at room temperature. 
   
   
       9 . The liquid pharmaceutical formulation according to  claim 8 , wherein said amylin agonist is pramlintide. 
   
   
       10 . A liquid pharmaceutical formulation comprising about 0.5 to 1.0% (w/v) of an amylin agonist, a pharmaceutically acceptable excipient, and insulin. 
   
   
       11 . The liquid pharmaceutical formulation according to  claim 10 , wherein said amylin agonist is pramlintide. 
   
   
       12 . The liquid pharmaceutical formulation according to  claim 10 , wherein said insulin is glargine. 
   
   
       13 . A formulation comprising about 1% to 98% (w/w) of an amylin agonist and about 1.0% to 20% (w/w) of at least one pharmaceutically acceptable excipient selected from the group consisting of a preservative, a penetration enhancer and a stabilizer. 
   
   
       14 . The formulation according to  claim 13  comprising about 80% to 90% (w/w) of said amylin agonist and about 10% to 20% (w/w) of said at least one pharmaceutically acceptable excipient. 
   
   
       15 . The formulation according to  claim 13  for oral administration, wherein said formulation is solid, wherein said pharmaceutically acceptable excipient is powdered, wherein said pharmaceutically acceptable excipient comprises about 1.0 to 20% (w/w) of said formulation, wherein said formulation comprises a penetration enhancer or stabilizer. 
   
   
       16 . The formulation according to  claim 15  wherein said formulation is encapsulated within a polymeric coating. 
   
   
       17 . The formulation according to  claim 15 , wherein said powdered excipient is lactose. 
   
   
       18 . The formulation according to  claim 15 , wherein said formulation comprises glargine. 
   
   
       19 . The formulation according to  claim 13 , wherein said amylin agonist is pramlintide. 
   
   
       20 . The formulation according to  claim 13  which is a solid, liquid, gel or semi-solid. 
   
   
       21 . The formulation according to  claim 13  which is lyophilized. 
   
   
       22 . The formulation according to  claim 13 , further comprising insulin. 
   
   
       23 . The formulation according to  claim 22 , wherein said insulin is glargine. 
   
   
       24 . The formulation according to  claim 13  for nasal, pulmonary or buccal delivery. 
   
   
       25 . The formulation according to  claim 24  comprising a penetration enhancer, or a stabilizer. 
   
   
       26 . The formulation according to  claim 24  further comprising a polymer. 
   
   
       27 . The formulation according to  claim 24  further comprising a preservative. 
   
   
       28 . The formulation according to  claim 13  for administration to a subject, wherein said formulation is administered in the form selected from the group consisting of oral delivery, a microcapsule delivery, a microsphere, an implant delivery, and a polymer matrix delivery. 
   
   
       29 . The formulation according to  claim 13  formulated in tablets or capsules for oral, sublingual or buccal delivery. 
   
   
       30 . The formulation according to  claim 13  formulated in powder form for nasal or pulmonary delivery. 
   
   
       31 . The formulation according to  claim 13  formulated for transdermal delivery. 
   
   
       32 . A method for treating diabetes in a patient in need of such treatment comprising administering a therapeutically effective amount of the formulation according to  claim 14  to the patient in need of such treatment. 
   
   
       33 . The method according to  claim 32  wherein insulin is admixed with said formulation. 
   
   
       34 . The method according to  claim 33  wherein said admixing step is simultaneous, or concerted and sequential. 
   
   
       35 . A liquid suspension formulation comprising about 0.5 to 90% (w/v) of an amylin agonist, insulin, about 1.0 to 10% (w/v) of a carbohydrate or a polyhydric alcohol, and about 0.02 to 0.5% (w/v) of an acetate, phosphate, citrate or glutamate buffer, and a liquid vehicle, wherein the formulation has a pH of about 3.5 to 5.0. 
   
   
       36 . The formulation according to  claim 35 , wherein said amylin agonist is pramlintide. 
   
   
       37 . The formulation according to  claim 35 , wherein said insulin is glargine.