Implantable device for long-term delivery of drugs
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.
1. A drug delivery device, comprising:
a non-erodible, non-porous housing member defining a reservoir, said housing member having a water impermeable outer surface and first and second opposing ends;
a microporous partition positioned in the first end of the housing member;
contained within said reservoir, a drug formulation comprised of a sparingly water soluble drug and a solubility-modifying excipient, said sparingly water soluble drug having a soluble form and an insoluble form, wherein the insoluble form of the drug is retained in the reservoir, and wherein said solubility-modifying excipient is capable of generating acid groups to provide a concentration of the drug, when the drug formulation is hydrated, sufficient to provide release of a therapeutic dose of the drug from the device for a period of between about 2-12 months, as the soluble form of the drug freely diffuses out of the device across said microporous partition.
2. The device according to claim 1 , wherein the housing member is a metal.
3. The device according to claim 1 , wherein the microporous partition is selected from a microporous polymer membrane, a sintered metallic membrane, and a ceramic membrane.
4. The device according to claim 1 , wherein the solubility-modifying excipient is a biocompatible, bioerodible polymer.
5. The device according to claim 4 , wherein the polymer is selected from the group of polylactides, polyglycolides, and copolymers thereof.
6. The device according to claim 5 , 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%.
7. The device according to claim 1 , wherein said drug is a neuroleptic agent.
8. The device according to claim 7 , wherein the neuroleptic agent is risperidone, 9-hydroxyrisperidone or a pharmaceutically acceptable salt thereof.
9. The device according to claim 7 , wherein the neuroleptic agent is olanzapine, paliperidone, asenapine, haloperidol or aripiprazole or a pharmaceutically acceptable salt thereof.
10. The device according to claim 7 , wherein the total amount of said neuroleptic agent loaded in said reservoir is greater than 100 mg.
11. The device according to claim 7 , wherein the drug is present in soluble and insoluble forms in a total amount of greater than 100 mg/mL.
12. The device according to claim 11 , wherein the soluble fraction of drug is less than 1% of the total.
13. The device according to claim 1 , wherein the drug is buprenorphine.
14. A method for treating a patient with a sparingly water soluble drug, comprising: implanting 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, and delivering a therapeutic dose of the drug for the period.