NON-AQUEOUS LIQUID FORMULATION FOR NASAL OR BUCCAL ADMINISTRATION

• US 20100035805A1
• Filed: 04/25/2007
• Published: 02/11/2010
• Est. Priority Date: 04/25/2006
• Status: Abandoned Application

• Current Assignee: OptiNose AS (OptiNose, Inc.)
• Original Assignee: OptiNose AS (OptiNose, Inc.)
• Inventors: Hafner, Peter Roderick
• Application Number:
  US12/298,292
• Publication Number:
  US 20100035805A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61M 15/0098 Activated by exhalation
• CPC Class Codes: A61P 5/04 for decreasing, blocking or antagonising the activity of the hypothalamic hormones
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH

Abstract

A formulation for administration to a nasal or buccal cavity of a subject which comprises a non-aqueous liquid environment, preferably an emollient oil base, and at least one active molecule, preferably a dopamine agonist and especially apomorphine, in solution or suspension therein, wherein in one embodiment the formulation has such a viscosity as to be delivered as a liquid jet from a spray pump which is capable of delivering an aerosol spray of an aqueous formulation.

Claims

1. A formulation which comprises a non-aqueous liquid environment and at least one active molecule for administration to a nasal or buccal cavity of a subject.

2. The formulation of claim 1, wherein the non-aqueous liquid environment comprises an emollient oil base.

3. The formulation of claim 2, wherein the emollient oil base includes at least one of a vegetable, mineral or animal oil, preferably the emollient oil base comprises a vegetable oil, and preferably the vegetable oil comprises at least one of almond oil, anise oil, apricot kernel oil, arachis oil, argan oil, avocado oil, borage oil, cajuput oil, canola oil, caraway oil, cassia oil, castor oil, cinnamon oil, citronella oil, clove oil, coconut oil, coriander oil, corn oil, cottonseed oil, eucalyptus oil, evening primrose oil, fennel oil, geranium oil, grapeseed oil, hazelnut oil, hemp oil, jojoba oil, juniper oil, lavender oil, lemon oil, macadamia oil, mace oil, melaleuca oil, neem oil, neroli oil, niaouli oil, nutmeg oil, olive oil, orange oil, palm oil, palm kernel oil, pine oil, poppyseed oil, pulegium oil, pumpkin seed oil, rapeseed oil, rice bran oil, rosehin oil rosemary oil, rue oil, safflower oil, sesame oil, spearmint oil, sovbean oil, sunflower oil, thyme oil, walnut oil and wheatgerm oil.

6. The formulation of claim 2, wherein the emollient oil base includes a fatty acid.

7. The formulation of claim 2, wherein the emollient oil base includes at least one of a monoglyceride, diglyceride or triglyceride.

8. The formulation of claim 1, wherein the at least one active molecule is a drug substance which degrades when in aqueous solution preferably the degradation is one of oxidation or hydrolysis.

10. The formulation of claim 8, wherein the at least one active molecule comprises an organic molecule with a molecular weight of less than about 1000.

11. The formulation of claim 8, wherein the at least one active molecule comprises a dopamine agonist, preferably the dopamine agonist comprises apomorphine or a pharmaceutically-acceptable derivative or analogue thereof.

13. The formulation of claim 8, wherein the at least one active molecule is a protein or a peptide.

14. The formulation of claim 13, wherein the at least one active molecule comprises an antidiurectic hormone, such as argipressin, lypressin, desmopressin, felypressin, ornipressin, terlipressin and vasopressin or a pharmaceutically-acceptable derivative or analogue thereof, an oxytocic hormone, such as carbetocin, demoxytocin and oxytocin or a pharmaceutically-acceptable derivative or analogue thereof, an oxytocin antagonist, such as atosiban or a pharmaceutically-acceptable derivative or analogue thereof, a corticotrophic hormone, such as corticotrophin and tetracosactide or a pharmaceutically-acceptable derivative or analogue thereof, a corticotrophic releasing hormone, such as corticorelin or a pharmaceutically-acceptable derivative or analogue thereof, an omatotrophic hormone, such as mecasermin, somtrem and somatropin or a pharmaceutically-acceptable derivative or analogue thereof, a somatotrophic hormone receptor antagonist, such as pegvisomant or a pharmaceutically-acceptable derivative or analogue thereof, an omatotrophic releasing hormone, such as sermorelin and somatorelin or a pharmaceutically-acceptable derivative or analogue thereof, a somatotrophic release inhibitor, such as lanreotide, octreotide, somatostatin and vapreotide or a pharmaceutically-acceptable derivative or analogue thereof a gonadotrophic hormone, such as choriogonadotrophin alfa, chorionic gonadotrophin, a follicle stimulating hormone, follitropin alfa, follitropin beta, a luteinising hormone, lutropin alfa, menotrophin and urofollitropin or a pharmaceutically-acceptable derivative or analogue thereof, a gonadotrophic releasing hormone, such as buserelin, deslorelin, gonadorelin, goserelin, histrelin, leuprorelin, naferlin and triptorelin or a pharmaceutically-acceptable derivative or analogue thereof, an onadotrophic releasing hormone antagonist, such as abarelix, cetorelix and ganirelix or a pharmaceutically-acceptable derivative or analogue thereof, a thyrotrophic hormone, such as thyrotrophin and thyrotrophin alfa or a pharmaceutically-acceptable derivative or analogue thereof, a thyrotrophic releasing hormone, such as posatirelin, protirelin and taltirelin or a pharmaceutically-acceptable derivative or analogue thereof, a lactotrophic hormone, such as prolactin or a pharmaceutically-acceptable derivative or analogue thereof, a metabolic peptide, such as insulin, an insulin-like growth factor, a glucagon, a growth hormone and PYY3-36 or a pharmaceutically-acceptable derivative or analogue thereof, a calcitonin or a pharmaceutically-acceptable derivative or analogue thereof, such as elcatonin and salcatonin, a melanocyte stimulating hormone, a nerve growth factor, an epidermal growth factor, an epoetin or a pharmaceutically-acceptable derivative or analogue thereof, an interleukin, a protein involved in one or both of blood coagulation and fibrinolysis, or an antibiotic, such as lactams, penicillins and cephalosporins.

38. The formulation of claim 8, wherein the at least one active molecule comprises water-labile esters, such as aspirin or a pharmaceutically-acceptable derivative or analogue thereof.

39. The formulation of claim 8, wherein the at least one active molecule comprises benzocain or a pharmaceutically-acceptable derivative or analogue thereof.

40. The formulation of claim 8, wherein the at least one active molecule comprises N-acetyl p-aminophenol or a pharmaceutically-acceptable derivative or analogue thereof.

41. The formulation of claim 8, wherein the at least one active molecule comprises a prostaglandin analogue or derivative.

42. The formulation of claim 8, wherein the at least one active molecule comprises indole-3-carbinol (I3C) or a pharmaceutically-acceptable derivative or analogue thereof.

43. The formulation of claim 8, wherein the at least one active molecule comprises water-labile amides.

44. The formulation of claim 1, wherein the formulation is substantially free of anti-microbial preservative.

45. The formulation of any of claim 1, wherein the at least one active molecule is in solution or suspension in the non-aqueous liquid environment.

47. The formulation of claim 1, wherein the viscosity of the formulation is such as to be delivered as a liquid jet from a spray pump which is capable of delivering an aerosol spray of an aqueous formulation or as a liquid spray from a spray pump which is capable of delivering an aerosol spray of an aqueous formulation.

49. The formulation of claim 1, wherein the formulation comprises a nasal formulation for administration to the nasal cavity.

50. The formulation of claim 1, wherein the formulation comprises a buccal formulation for administration to the buccal cavity preferably for sub-lingual administration.

52. A method of treating breakthrough dyskinesia or sexual dysfunction, which comprises the step of intranasally administering the formulation of claim 49 to a nasal airway of a subject.

53. The method of claim 52, wherein the formulation is delivered as a liquid jet or a liquid spray.

4. (canceled)

5. (canceled)

9. (canceled)

12. (canceled)

15-37. -37. (canceled)

46. (canceled)

48. (canceled)

51. (canceled)

54-58. -58. (canceled)