Controlled release formulations of octreotide

Abstract

A formulation of octreotide or pharmaceutically acceptable salts thereof, which provides controlled release of a therapeutically effective amount of octreotide for a period of at least about two months. Methods of treating acromegaly, decreasing growth hormone, decreasing IGF-1, and treating conditions associated with carcinoid tumors and VIPomas by administering a controlled release formulation of octreotide are provided herein.

1 .- 23 . (canceled) 
     
     
         24 . A method of treating a patient suffering from a condition associated with carcinoid tumors or suffering from one or more symptoms associated with such condition, the method comprising:
 implanting subcutaneously into a patient in need thereof at least one implant comprising a hydrophilic polymer and a pharmaceutical formulation comprising octreotide acetate, 0.5 to 20% w/w of hydroxypropylcellulose, and 0.5 to 5% w/w of magnesium stearate, wherein the at least one implant is implanted in a dry state;   wherein the hydrophilic polymer comprises a copolymer of at least two hydrophilic, ethylenically unsaturated monomers, wherein the at least two hydrophilic, ethylenically unsaturated monomers are 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate, and wherein the copolymer comprises about 20% by weight of 2-hydroxyethyl methacrylate and about 80% by weight hydroxypropylmethacrylate;   wherein the pharmaceutical formulation is contained within the hydrophilic polymer;   wherein the pharmaceutical formulation contains between about 20 to about 150 milligrams of octreotide acetate; and   wherein the at least one implant releases a therapeutically effective amount of the octreotide acetate to the patient at a rate of about 30 to 300 μg/day to provide an in vivo average C ss  in the patient of about 0.1 ng/ml to about 9 ng/ml of octreotide over a period of at least about two months to about two years.   
     
     
         25 . The method of  claim 24 , wherein the pharmaceutical formulation contains from about 40 to about 90 milligrams of octreotide acetate. 
     
     
         26 . The method of  claim 25 , wherein the pharmaceutical formulation contains about 50 milligrams of the octreotide acetate. 
     
     
         27 . The method of  claim 25 , wherein the pharmaceutical formulation contains about 80 milligrams of the octreotide acetate. 
     
     
         28 . The method of  claim 24 , wherein the effective amount of the octreotide provides an in vivo average C ss  in the patient of about 1 ng/ml to about 2 ng/ml of octreotide. 
     
     
         29 . The method of  claim 24 , wherein the at least one implant releases a therapeutically effective amount of the octreotide over about six months. 
     
     
         30 . The method of  claim 24 , wherein the at least one implant is two or more implants. 
     
     
         31 . The method of  claim 24 , wherein the at least one implant is implanted in a hydrated state. 
     
     
         32 . The method of  claim 24 , wherein the at least one implant releases a therapeutically effective amount of the octreotide acetate to the patient at a rate of about 30 to 250 μg/day. 
     
     
         33 . The method of  claim 24 , wherein the at least one implant releases a therapeutically effective amount of the octreotide acetate to the patient at a rate of about 100 μg/day. 
     
     
         34 . The method of  claim 24 , wherein the at least one implant releases a therapeutically effective amount of the octreotide acetate to the patient at a rate of about 100 to 300 μg/day.