Systems and processes for spray drying hydrophobic and hydrophilic components

• US 8,802,149 B2
• Filed: 05/20/2009
• Issued: 08/12/2014
• Est. Priority Date: 12/31/1996
• Status: Expired due to Fees

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Novartis Pharma AG (Novartis Ag)
• Inventors: Gordon, Marc S., Clark, Andrew, Brewer, Thomas K.
• Primary Examiner(s): CHANNAVAJJALA, LAKSHMI SARADA
• Application Number:
  US12/469,634
• Publication Number:
  US 20090285905A1
• Time in Patent Office: 1,910 Days
• Field of Search: None
• US Class Current: 424/489
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules

Abstract

Methods for preparing dry powders having hydrophobic and hydrophilic components comprise combining solutions of the components and spray drying them simultaneously in a spray dryer. The hydrophilic and hydrophobic component are separately dissolved in separate solvents and directed simultaneously through a nozzle, usually a coaxial nozzle, into the spray dryer. The method provides dry powders having relatively uniform characteristics.

Claims

1. A dry powder drug composition in the form of a unit dose, the composition comprising discrete particles having an average particle size of less than 10 μ

m for delivery to the lungs as a dry powder, wherein each discrete particle comprises a drug component, a hydrophobic component having a water solubility of less than 5 mg/mL, and a hydrophilic component having a water solubility of greater than 5 mg/mL, wherein the unit dose is contained in a unit dose receptacle that is insertable into a dry powder inhaler.

2. The dry powder drug composition of claim 1, wherein the hydrophilic component comprises water soluble polymer or water soluble carbohydrate.

3. The dry powder drug composition of claim 1, wherein the hydrophilic component comprises a material selected from the group consisting of polyvinylpyrrolidone, lactose, sodium citrate, mannitol, pectin, povidone, citric acid, sodium chloride, salts thereof, and hydrates thereof.

4. The dry powder drug composition of claim 1, wherein at least about 90% by weight of the particles have the average particle size within a range from about 0.1 μ

m to about 7 μ

m.

5. The dry powder drug composition of claim 1, wherein the average particle size is within a range from about 0.4 μ

m to about 4 μ

m.

6. The dry powder drug composition of claim 1, wherein the hydrophilic component comprises a citrate.

7. The dry powder drug composition of claim 6, wherein the hydrophilic component comprises sodium citrate.

8. The dry powder drug composition of claim 1, wherein at least about 90% by weight of the particles have the average particle size within a range from about 0.1 μ

m to about 7 μ

m.

9. The dry powder drug composition of claim 8, wherein at least about 85% by weight of the particles have the average particle size within a range from about 0.4 μ

m to about 5 μ

m.

10. The dry powder drug composition of claim 9, wherein the water solubility of the hydrophilic component is greater than 50 mg/mL.

11. The dry powder drug composition of claim 10, wherein the water solubility of the hydrophilic component is greater than 100 mg/mL.

12. The dry powder drug composition of claim 1, wherein the discrete particles comprise spray-dried particles.

13. The dry powder drug composition of claim 1, where the discrete particles having an average particle size within a range from about 0.4 μ

m to about 5 μ

m for at least about 85% by weight of the particles for delivery to the lungs as a dry powder and wherein the hydrophilic excipient has a water solubility of greater than 50 mg/mL.

14. The dry powder drug composition of claim 13, wherein the water solubility of the hydrophobic component is less than 1 mg/mL.

15. The dry powder drug composition of claim 13, wherein the water solubility of the hydrophilic excipient is greater than 100 mg/mL.

16. The dry powder drug composition of claim 15, wherein the water solubility of the hydrophobic component is less than 1 mg/mL.

17. The dry powder drug composition of claim 13, wherein the discrete particles comprise spray-dried particles.

18. The dry powder drug composition of claim 1, wherein the hydrophobic component has a water solubility of less than 1 mg/mL.

19. The dry powder drug composition of claim 18, wherein the discrete particles comprise spray-dried particles.

20. The dry powder drug composition of claim 1, wherein the drug component comprises a hydrophobic drug having a water solubility of less than 5 mg/mL.

21. The dry powder drug composition of claim 20, wherein the drug component comprises one or more drugs selected from the group consisting of budesonide, testosterone, progesterone, estrogen, flunisolide, triamcinolone, beclomethasone, betamethasone, dexamethasone, fluticasone, methylprednisolone, prednisone, hydrocortisone, cyclosporin, all-cis retinoic acid, 13-trans retinoic acid, vitamin D, vitamin E, vitamin K, a prostaglandin, a leukotriene, prostacyclin, tetrahydrocannabinol, a lung surfactant lipid, a lipid soluble antioxidant, a hydrophobic antibiotic, a hydrophobic chemotherapeutic drug, amphotericin B, and adriamycin.

22. The dry powder drug composition of claim 1, wherein the drug component comprises a hydrophilic drug having a water solubility of greater than 5 mg/mL.

23. The dry powder drug composition of claim 1, wherein the unit dose receptacle comprises a capsule.

24. The dry powder drug composition of claim 23, wherein the capsule is made or gelatin or plastic.

25. The dry powder drug composition of claim 1, wherein the unit dose receptacle comprises a foil layer.

26. A dry powder drug composition comprising discrete particles having an average particle size of less than 10 μ

m for delivery to the lungs as a dry powder, wherein each discrete particle comprises a hydrophobic component having a water solubility of less than 5 mg/mL, a hydrophilic component having a water solubility of greater than 5 mg/mL, and a chloride salt.

27. The dry powder drug composition of claim 26, wherein each discrete particle further comprises a salt of an acid.

28. The dry powder drug composition of claim 27, wherein the salt of an acid comprises a citrate.

29. The dry powder drug composition of claim 26 wherein the chloride salt comprise sodium chloride.

30. A dry powder drug composition comprising discrete particles having an average particle size of less than 10 μ

m for delivery to the lungs as a dry powder, wherein each discrete particle comprises a hydrophobic component having a water solubility of less than 5 mg/mL, a hydrophilic component having a water solubility of greater than 5 mg/mL, and a salt of an acid.

31. The dry powder drug composition of claim 30, wherein the salt of an acid comprises a citrate.