Method of treating schizophrenia with an implantable device for long-term delivery of drugs

Abstract

A device for sustained delivery of a poorly water soluble drug is described. A drug reservoir within the device, when in operation, contains an aqueous suspension of the drug mixed with a suspension of an excipient that, in one embodiment, generates acidic groups for a sustained period of time to maintain a desired pH in the aqueous suspension that in turn provides a constant concentration of a soluble form of the drug.

It is claimed: 
     
         1 . A method for treating a patient suffering from schizophrenia, comprising: providing a device comprising a microporous partition with pores having a pore size and with a porosity, a reservoir and a formulation contained in the reservoir, the formulation comprising a sparingly water soluble drug having a soluble form and an insoluble form and a solubility-modifying excipient that generates acidic groups for a period of between about 2-12 months to provide, when the formulation is hydrated, a concentration of drug in the soluble form that freely diffuses out of the device across the microporous partition and a concentration of drug in the insoluble form that is retained in the device by the microporous partition, to thereby deliver for the period a dose of the drug effective for treating schizophrenia. 
     
     
         2 . The method according to  claim 1 , wherein the sparingly water soluble drug is a neuroleptic agent. 
     
     
         3 . The method according to  claim 2 , wherein the neuroleptic agent is provided at a dose of about 0.5 mg/day to about 3 mg/day. 
     
     
         4 . The method according to  claim 3 , wherein the neuroleptic agent is provided for a period of about 2 month to about 6 months. 
     
     
         5 . The method according to  claim 2 , wherein the total amount of said neuroleptic agent loaded in said reservoir is greater than 100 mg. 
     
     
         6 . The method according to  claim 2 , wherein the neuroleptic agent is present in soluble and insoluble forms in a total amount of greater than 100 mg/mL. 
     
     
         7 . The method according to  claim 6 , wherein the soluble fraction of drug is less than 1% of the total. 
     
     
         8 . The method according to  claim 2 , wherein the neuroleptic agent is risperidone, 9-hydroxyrisperidone or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method according to  claim 2 , wherein the neuroleptic agent is olanzapine, paliperidone, asenapine, haloperidol or aripiprazole or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method according to  claim 1 , wherein the device comprises a non-erodible, non-porous housing member. 
     
     
         11 . The method according to  claim 10 , wherein the housing member is a metal. 
     
     
         12 . The method according to  claim 1 , wherein the microporous partition is selected from a microporous polymer membrane, a sintered metallic membrane, and a ceramic membrane. 
     
     
         13 . The method according to  claim 1 , wherein the solubility-modifying excipient is a biocompatible, bioerodible polymer. 
     
     
         14 . The method according to  claim 13 , wherein the polymer is selected from the group of polylactides, polyglycolides, and copolymers thereof. 
     
     
         15 . The method according to  claim 14 , wherein the polymer is a co-polymer of polylactic acid and polyglycolic acid monomeric units, wherein the polylactic acid content is between about 50% to 100%. 
     
     
         16 . The method of  claim 1 , further comprising administering or instructing to administer the device to the subject. 
     
     
         17 . The method of  claim 16 , wherein said administering comprises implanting and said instructing to administer comprises instructing to implant. 
     
     
         18 . The method of  claim 17 , wherein said implanting or instructing to implant comprises subcutaneous implantation.