Delivery of dry formulations of octreotide

Abstract

Methods and devices are described for delivering octreotide to a patient, comprising implanting a controlled release composition for delivering octreotide, wherein the composition does not require hydration prior to implantation, and wherein the composition optionally comprises a release agent.

1 . A method of delivering octreotide to a subject with a substantially zero-order release profile over an extended period of time, but no less than about six months, the method comprising:
 subcutaneously implanting in the subject at least one implantable device;   wherein:   the at least one implantable device comprises
 a composition comprising octreotide encased in a hydrophilic polymer; and 
   the implantable device is implanted in a dry state, such that the subject receives on a daily basis over a period of at least about six months dose amounts of octreotide, which are effective to treat the subject.   
     
     
         2 . The method of  claim 1 , wherein the hydrophilic polymer comprises a co-polymer obtained from the co-polymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers 
     
     
         3 . The method of  claim 1 , wherein the hydrophilic polymer comprises one or more methacrylate-based polymers. 
     
     
         4 . The method of  claim 1 , wherein the hydrophilic polymer comprises a hydrophilic polyurethane. 
     
     
         5 . The method of  claim 1 , wherein the octreotide is in free form, salt form or in the form of a complex thereof. 
     
     
         6 . The method of  claim 1 , wherein the octreotide is octreotide acetate. 
     
     
         7 . The method of  claim 1 , wherein the subject is afflicted with a GH or IGF-1 hormone disorder or its symptoms. 
     
     
         8 . The method of  claim 7 , wherein the GH or IGF-1 disorder is acromegaly. 
     
     
         9 . The method of  claim 1 , wherein the subject receives octreotide at an average rate ranging from about 75 μg per day to about 300 μg per day over a period of at least about six months. 
     
     
         10 . The method of  claim 1 , wherein the dose amounts of octreotide received by the subject result in octreotide serum levels ranging from about 0.5 ng/ml to about 2 ng/ml. 
     
     
         11 . The method of  claim 1 , wherein the subject receives an effective amount of octreotide for a period of at least about twelve months. 
     
     
         12 . The method of  claim 1 , wherein the dose amounts of octreotide received by the subject result in octreotide serum levels ranging from about 0.8 ng/ml to about 1.8 ng/ml. 
     
     
         13 . The method of  claim 1 , wherein the dose amounts of octreotide received by the subject result in C max  for octreotide serum levels below about 1.3 ng/ml. 
     
     
         14 . The method of  claim 1 , wherein the dose amounts of octreotide received by the subject result in C max  for octreotide serum levels below about 1.0 ng/ml. 
     
     
         15 . The method of  claim 1 , wherein release of octreotide occurs at least three to about ten days after implantation. 
     
     
         16 . The method of  claim 1 , wherein the subject is afflicted with a condition selected from the group consisting of carcinoid syndrome, VIPomas, neuroendocrine tumors, proliferative diabetic retinopathy, rosacea, pancreatitis, gastrointestinal bleeding, pancreatic and intestinal fistulas, Graves-Basedow opthalmopathy, glaucoma, and symptoms associated with chemotherapy or AIDS. 
     
     
         17 . The method of  claim 2 , wherein the hydrophilic, ethylenically unsaturated monomers are selected from 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate monomers. 
     
     
         18 . The method of  claim 2 , wherein the copolymer comprises about 20% of 2-hydroxyethyl methacrylate and about 80% hydroxypropyl methacrylate.