Claims for Patent: 10,085,936

Summary for Patent: 10,085,936

Title:	Antipsychotic injectable depot composition
Abstract:	The present invention is directed to a composition that can be used to deliver an antipsychotic drug such as risperidone as an injectable in-situ forming biodegradable implant for extended release providing therapeutic plasma levels from the first day. The composition is in the form of drug suspension on a biodegradable and biocompatible copolymer or copolymers solution using water miscible solvents that is administered in liquid form. Once the composition contacts the body fluids, the polymer matrix hardens retaining the drug, forming a solid or semisolid implant that releases the drug in a continuous manner. Therapeutic plasma levels of the drug can be achieved since the first day up to at least 14 days or more even up to at least four weeks.
Inventor(s):	Gutierro Aduriz Ibon, Gomez Ochoa Maria Teresa
Assignee:	LABORATORIOS FARMACEUTICOS ROVI, S.A.
Application Number:	US13690647
Patent Claims:	1. An injectable depot composition consisting of:drug, which is risperidone present as particles having a particle size distribution as follows: not more than 10% of the total volume of drug particles is less than 10 microns in size, not more than 10% of the total volume of drug particles is greater than 225 microns in size, and the d0.5 of the size distribution is in the range of about 60-130 microns; and DMSO; and', 'biocompatible poly(lactide-co-glycolide) (PLGA) copolymer comprising lactic acid and glycolic acid monomers, wherein the monomers are present at a monomer ratio of lactic to glycolic acid of 48:52 to 52:48, the copolymer has an inherent viscosity in the range of 0.25-0.48 dl/g as measured in chloroform at 25° C. and at a concentration of 0.1% wt/v with a Ubbelohde size 0c glass capillary viscometer; wherein', 'the polymeric solution has a viscosity in the range of about 0.7 Pa.s to about 3.0 Pa.s; and wherein, 'polymeric solution consisting ofthe drug content is about 13% wt with respect to the total composition weight;the DMSO to drug mass ratio is about 4:1 to 5:1;the polymeric solution to drug mass ratio is about 6.5:1 to 7:1.2. The injectable depot composition according to claim 1 , wherein the drug/copolymer mass ratio is about 33% claim 1 , expressed as the weight percentage of the drug with respect to the drug plus copolymer.3. The injectable depot composition according to claim 1 , wherein the DMSO to drug mass ratio is about 4.66:1.4. The injectable depot composition according to claim 1 , wherein the mass ratio between the weight of the polymeric solution and the weight of the drug is about 6.66:1.5. The injectable depot composition according to claim 1 , wherein the composition is a sterile composition.6. A pharmaceutical kit suitable for the in situ formation claim 1 , in a subject claim 1 , of a biodegradable implant comprising the injectable depot composition according to claim 1 , wherein claim 1 , prior to mixing with the DMSO the drug and the biocompatible copolymer are contained in a first container claim 1 , and the DMSO is contained in a second claim 1 , separate container.7. The pharmaceutical kit according to claim 6 , wherein at least one of the first and second containers is a syringe claim 6 , a vial claim 6 , or a cartridge.8. The pharmaceutical kit according to claim 7 , wherein both the first and the second containers are disposable syringes.9. The pharmaceutical kit according to claim 8 , wherein the syringes are connectable through a connector device or a direct thread.10. The injectable depot composition according to claim 1 , wherein at least 95% wt of the copolymer is dissolved in the composition prior to placement in an aqueous environment.11. The injectable depot composition according to claim 1 , wherein ≥1% wt of the drug is dissolved in the DMSO or the composition prior to placement in an aqueous environment.12. The injectable depot composition according to claim 1 , wherein the composition is injectable by hand through a 18 to 22 gauge needle.13. The injectable depot composition according to claim 1 , wherein claim 1 , prior to inclusion in the injectable composition claim 1 , the copolymer has been irradiated with about 10 KGy to about 25 KGy of beta-radiation.14. The injectable depot composition of claim 1 , wherein the composition releases at least 0.5% wt and no more than 8% wt of its charge of risperidone within 24 hours after being placed in an aqueous environment.15. The injectable depot composition of claim 1 , wherein the composition provides a substantially level plasma concentration profile of within ±15% of the average or mean plasma concentration during a period of at least 14 days following administration of the composition to a subject.17. The injectable depot composition of claim 1 , wherein: a) the mass ratio of the amount of polymeric solution to the amount of drug in the injectable composition is about 6.66:1; and b) the DMSO to drug mass ratio is about 4.66:1.18. The injectable depot composition of claim 1 , wherein the composition provides a substantially level plasma concentration profile of within ±10% of the average or mean plasma concentration during a period of at least 14 days following administration of the composition to a subject.20. The injectable depot composition of claim 1 , wherein the composition provides a substantially level plasma concentration profile of within ±20% of the average or mean plasma concentration during a dosing period of at least 28 days following administration of the composition to a subject.