Pharmaceutical Compositions Comprising Multi-Component Crystalline Particles Suitable for Use in Inhalation Therapy

• US 20150366804A1
• Filed: 01/29/2014
• Published: 12/24/2015
• Est. Priority Date: 01/31/2013
• Status: Active Grant

• Current Assignee: Circassia Limited (Circassia Group Plc)
• Original Assignee: Prosonix Ltd. (Circassia Group Plc)
• Inventors: Burns, John, Parikh, Dipesh
• Granted Patent: US 9,682,038 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• 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 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/44 Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids

Abstract

Pharmaceutical compositions comprising multi-component crystalline particles suitable for use in inhalation therapy and for delivery by oral or nasal inhalation are provided, wherein said compositions additionally comprise particles of at least one additional active agent. Also provided are methods of preparation of the compositions and their use in medicine.

Claims

1. A composition for inhalation therapy comprising multi-component crystalline particles and also particles of fluticasone propionate, wherein the multi-component crystalline particles comprise glycopyrronium bromide and salmeterol xinafoate (GB-SX) as active ingredients and are substantially free of excipients and agents other than the active ingredients.

2. A composition according to claim 1 wherein the particles of fluticasone propionate are crystalline.

4. A composition according to claim 1 for the treatment of asthma, COPD or cystic fibrosis.

12. A composition according to claim 1 wherein the multi-component particles comprise a eutectic composition.

13. A composition according to claim 1 deliverable from a pressurised metered dose inhaler, a dry powder inhaler or a breath activated nasal inhaler.

14. A composition deliverable from a pressurised metered dose inhaler according to claim 13 which is substantially free of excipients and er-agents other than the active agents and a pharmaceutically acceptable propellant.

15. A composition according to claim 1 wherein the multi-component particles are prepared by a process comprising the steps:

(i) forming a solution of glycopyrronium bromide and salmeterol xinafoate in a solvent;

(ii) subjecting the solution to a process selected from the group consisting of rapid precipitation, freeze drying, lyophilisation, rapid expansion of supercritical solutions, spray drying or mixtures thereof, wherein the glycopyrronium bromide and salmeterol xinafoate are converted into a substantially dry solid material;

iii) optionally isolating the solid material from the liquid and/or gaseous components of the process of step (ii);

(iv) treating said dry solid material from step (ii) or step (iii) with a non-solvent therefor;

(v) applying ultrasound to the solid material from step (iv) when it is in contact with said non-solvent; and

(vi) separating and/or drying the resultant solid material from step (v).

16. A composition according to claim 1 wherein the multi-component particles are prepared in the presence of ultrasound irradiation in a process comprising contacting a solution of glycopyrronium bromide and salmeterol xinafoate in a first flowing stream with an anti-solvent in a second flowing stream, causing the mixing thereof, and collecting the crystalline particles that are generated.

17. A dry powder inhaler, a pressurised metered dose inhaler, or a breath activated nasal inhaler comprising a composition according to claim 1.

18. A method of treating a respiratory disease or disorder or a pulmonary disease or disorder in a patient wherein the method comprises a composition according to claim 1.

20. A composition according to claim 1 for treatment of a respiratory disease or disorder or a pulmonary disease or disorder.

22. A method of treating a respiratory disease or disorder or a pulmonary disease or disorder in a patient according to claim 18 wherein the composition is administered by a dry powder inhaler, a pressurised metered dose inhaler, or a breath activated nasal inhaler.

23. An inhaler according to claim 17 for treatment of a respiratory disease or disorder or a pulmonary disease or disorder.

3. (canceled)

5-11. -11. (canceled)

19. (canceled)

21. (canceled)