Claims for Patent: 8,236,755

Summary for Patent: 8,236,755

Title:	Opioid depot formulations
Abstract:	The present invention relates to pre-formulations comprising low viscosity, non-liquid crystalline, mixtures of:
Inventor(s):	Thuresson Krister, Tiberg Fredrik, Johansson Markus, Harwigsson Ian, Joabsson Fredrik, Johnsson Markus
Assignee:	Camurus AB
Application Number:	US11798495
Patent Claims:	1. A non-liquid crystalline formulation precursor for the in vivo generation of a liquid crystalline lipid composition for the controlled release of at least one opioid bioactive agent following parenteral administration , said formulation precursor comprising: a) a minimum of 18 wt. % of at least one neutral diacyl lipid or a mixture of a neutral diacyl lipid and at least one tocopherol;', 'b) at least one phospholipid; and', 'c) a biocompatible, oxygen containing, low viscosity organic solvent comprising ethanol; and, 'i) A low-viscosity, non-liquid crystalline mixture having a viscosity of 1 to 1000 mPas at 20° C. and comprisingii) at least one opioid bioactive agent dissolved or dispersed in the low viscosity mixture;wherein the pre-formulation forms, at least one non-lamellar liquid crystalline phase structure in vivo upon contact with an aqueous fluid.2. The formulation precursor as claimed in wherein said non-lamellar liquid crystalline phase structure is bioadhesive.3. The formulation precursor as claimed in wherein component a) consists essentially of diacyl glycerols.4. The formulation precursor as claimed in wherein component a) consists essentially of a mixture of glycerol dioleate and tocopherol.5. The formulation precursor as claimed in wherein component b) is selected from phosphatidylcholines claim 1 , phosphatidylethanolamines claim 1 , phosphatidylserines claim 1 , phosphatidylinositols and mixtures thereof.6. The formulation precursor as claimed in having a molecular solution claim 1 , Land/or Lphase structure.7. The formulation precursor as claimed in having a ratio of a) to b) of between 95:5 and 5:95 by weight.8. The formulation precursor as claimed in having 0.5 to 50% component c) by weight of components a)+b)+c).9. The formulation precursor as claimed in additionally comprising up to 10% by weight of a)+b) of a charged amphiphile.10. The formulation precursor as claimed in wherein said active agent is selected from natural opium alkaloids claim 1 , semi-synthetic opioids and synthetic opioids.11. The formulation precursor as claimed in wherein said synthetic opioid is selected from bezitramide claim 10 , methadone claim 10 , LAAM claim 10 , loperamide claim 10 , diphenoxylate claim 10 , buprenorphine and etorphine.12. The formulation precursor as claimed in wherein said synthetic opioid is buprenorphine or methadone.13. The formulation precursor as claimed in which is administrable by injection.14. The formulation precursor as claimed in which is administrable by spraying claim 1 , dipping claim 1 , rinsing claim 1 , application from a pad or ball roller claim 1 , painting claim 1 , dropping claim 1 , aerosol spraying or pump spraying.15. The method of delivery of an opioid bioactive agent to a human or non-human mammalian body claim 1 , the method comprising administering a formulation precursor comprising: a) a minimum of 18 wt. % of a component consisting of at least one neutral diacyl lipid or a mixture of a neutral diacyl lipid and at least one tocopherol;', 'b) at least one phospholipid; and', 'c) at least one biocompatible, oxygen containing, low viscosity organic solvent;, 'i) non-liquid crystalline, low viscosity mixture having a viscosity of 1 to 1000 mPas at 20° C. and comprisingii) at least one opioid bioactive agent dissolved or dispersed in the low viscosity mixture,whereby said administration serves to form at least one non-lamellar liquid crystalline phase structure in vivo upon, contact with an aqueous fluid.16. A method as claimed in wherein said formulation precursor is a formulation precursor as claimed in .17. The method as claimed in wherein said formulation precursor is administered by a method selected from subcutaneous injection claim 15 , intramuscular injection claim 15 , intra-cavity injection through tissue claim 15 , intra-cavity injection into an open cavity without tissue penetration claim 15 , spraying claim 15 , rolling claim 15 , wiping claim 15 , dabbing claim 15 , painting claim 15 , rinsing claim 15 , or dropping.18. A method for the preparation of a non-lamellar liquid crystalline composition comprising exposing a formulation precursor comprising: a) a minimum of 18 wt. % of a component comprising at least one neutral diacyl lipid or a mixture of a neutral diacyl lipid and at least one tocopherol;', 'b) at least one phospholipid; and', 'c) at least one biocompatible, oxygen containing, low viscosity organic solvent;, 'i) non-liquid crystalline, low viscosity mixture having a viscosity of 1 to 1000 mPas at 20° and comprisingii) at least one opioid bioactive agent dissolved or dispersed in the low viscosity mixture,to an aqueous fluid in vivo.19. The method as claimed in wherein said formulation precursor is a formulation precursor as claimed in .20. A process for the formation of a formulation precursor for the administration of an opioid bioactive agent to a mammalian subject claim 15 , said process comprising forming a non-liquid crystalline claim 15 , low viscosity mixture having a viscosity of 1 to 1000 mPas at 20° C. and comprising:a) a minimum of 18 wt. % of a component consisting of at least one neutral diacyl lipid or a mixture of a diacyl lipid and at least one tocopherol;b) at least one phospholipid;c) at least one biocompatible, oxygen containing low viscosity, organic solvent;and dissolving or dispersing at least one opioid bioactive agent in the low viscosity mixture, or in at least one of components a, b or c prior to forming the low viscosity mixture.21. The process as claimed in wherein said formulation precursor is a formulation precursor as claimed in .22. A method of treatment or prophylaxis of a human or non-human animal subject comprising administration of the formulation as claimed in .23. The method of for the treatment of a condition selected from pain claim 22 , diarrhoea claim 22 , depression claim 22 , opioid dependence claim 22 , opioid addiction claim 22 , and the symptoms of opioid withdrawal.24. The method of for prophylaxis against the symptoms of opioid withdrawal.25. The method of wherein opioid dependence claim 23 , opioid addiction claim 23 , and/or the symptoms of opioid withdrawal result from opioid abuse.