GB2606306A - Lactose particles and method of production thereof - Google Patents
Lactose particles and method of production thereof Download PDFInfo
- Publication number
- GB2606306A GB2606306A GB2210051.5A GB202210051A GB2606306A GB 2606306 A GB2606306 A GB 2606306A GB 202210051 A GB202210051 A GB 202210051A GB 2606306 A GB2606306 A GB 2606306A
- Authority
- GB
- United Kingdom
- Prior art keywords
- particles
- adherent
- spherical
- solvent
- lactose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Processes Of Treating Macromolecular Substances (AREA)
Abstract
Spherical particles and method of producing the same, said particles are disaccharide particles, wherein said disaccharide is lactose and the particles are substantially spherical in shape and/or hollow.
Claims (45)
1. A plurality of disaccharide particles, wherein said disaccharide is lactose and the particles are substantially spherical in shape and/ or hollow.
2. Particles according to claim 1 wherein the particles are monodisperse and/ or have a narrow size distribution.
3. Particles according to claims 1 or 2 wherein the particles are highly spherical or perfectly spherical particles.
4. Particles according to claims 1-3 wherein the particles contain at least one anti adherent .
5. Particles according to claim 4 wherein the anti adherent is a hydrophilic and/ or non-ionic compound or excipient.
6. Particles according to claim 5 wherein the anti-adherent is polyvinyl pyrrolidone (PVP).
7. Particles according to claim 6 wherein PVP is a synthetic hydrophilic non-ionic excipient divided into viscosity grades k-15, k-30, k-60, or k-90 with the average molecular weight being 10,000, 40000, 160000 and 360000, respectively .
8. Particles according to claim 1 wherein the lactose is oc-lactose monohydrate.
9. Particles according to claim 1 wherein the lactose is anhydrous oc-lactose.
10. Particles according to claim 3 wherein the particles have an elongation ratio of 0.9 - 1.1.
11. Particles according to claim 10 wherein the particles are spherical with an elongation ration of 1.
12. Particles according to any preceding claim wherein the particles are provided as a powder .
13. Particles according to claim 1 wherein the volume mean diameter (VMD) of the particles is, or is substantially, 75 pm.
14. Particles according to any preceding claim for use as a carrier in a dry powder for inhalation
15. Particles according to any preceding claim compressed into tablet form.
16. Particles according to claim 14 wherein are a carrier for use in an inhaled pharmaceutical compositions.
17. Particles according to claim 16 wherein said carrier has a sieve size diameter equal or smaller than 250 micrometres.
18. Particles according to claim 17 wherein the carrier has a sieve size diameter equal or smaller than 45 micrometres.
19. Particles according to claim 15 wherein the ratio of drug to carrier ranges from 1: 67.5 w/w to 1:5 w/w.
20. A crystallisation method to produce substantially spherical lactose particles comprising; - dissolving at least one anti-adherent polymer in an aqueous medium to form a solution; - dissolving lactose in the anti- adherent polymer solution; - preparing an anti-solvent mixture containing two miscible anti-solvents - wherein the anti-adherent polymer is substantially soluble in one of the anti solvents and insoluble in the other anti-solvent; and - mixing the antisolvent mixture with the polymer solution.
21. A method according to claim 20 wherein the volume of the anti-solvent in which the polymer is insoluble is at least equal or greater to the volume of the solvent in which the polymer is soluble.
22. A method according to claim 20 wherein the mixing of the antisolvent mixture and the polymer solution is under controlled agitation and/ or controlled temperature;
23. A method according to claim 20 wherein the solvent and/or anti-solvent is removed thereby harvesting the crystalline spherical particles containing an anti adherent.
24. A method according to claim 20 wherein the two miscible anti-solvents have substantially similar or identical densities.
25. A method according to claim 20 wherein the anti-adherent is a polymer.
26. A method according to claim 25 wherein the anti-adherent is polyvinyl pyrrolidone.
27. A method according to claim 20 wherein the surface roughness of the spherical particles is dictated by the solubility of the anti-adherent in the solvent/ anti-solvent mixture.
28. A method according to claim 20 wherein the aqueous solution comprises from about 0.01% to about 2% weight of the anti-adherent polymer per volume of the aqueous medium.
29. A method according to claim 20 wherein the anti-solvents have each a density of 0.79 g/ cm3 .
30. A method according to claim 20 wherein the anti-solvents include any one or any combination of methanol, methylated spirits, ethanol, ethylated spirits, propan- l-ol, isopropyl alcohol, 1,3-propanediol, acetone, ethyl acetate.
31. A method according to claim 20 wherein the anti-solvent mixture comprises ethanol and acetone.
32. A method according to claim 31 wherein at least some of the ethanol is replaced with 1,3-propanediol to control particle size .
33. A method according to claim 21 wherein the volume of ethanol in the volume of anti-solvent mixture varies from 0.1% to 50%.
34. A method according to claim 20 wherein the anti-adherent polymer solution when mixed with anti-solvent mixture constitutes or forms a crystallisation medium.
35. A method according to claim 34 wherein the temperature of the crystallisation medium is between -10 °C to + 30 °C .
36. A method according to claim 20 wherein the method includes adding any one or any combination of; a drug, a pharmaceutical excipient, a particle composite comprising of one or more excipients and a drug.
37. A method according to claim 36 wherein one or more substances are introduced to the anti-solvent mixture to form a spherical particle composite comprising all the substances in one particle or each substance forms its own spherical particles in the same crystallisation medium, or said one or more substances are introduced to the anti- adherent polymer solution
38. A method according to claim 37 wherein said substances include a drug substance, an excipient or a mixture comprising one or more drugs with one or more excipients, suitable for use and/ or administration by oral route or in an inhaled pharmaceutical composition .
39. A method according to claim 34 wherein the particles are separated from the crystallisation medium by discarding the crystallisation medium to leave solid particles which are harvested by exposing said particles to a volatile solvent.
40. A method according to claim 39 wherein the particles are dispersed in a volatile solvent before being emptied on a glass slab or conveyer belt.
41. A method according to claim 20 wherein particles are treated by contacting the spherical particles with a hydrophobic coating solution and/ or suspension.
42. A method according to claim 41 wherein the crystalline spherical particles containing an anti-adherent are contacted with polylactic co-glycolic acid (PLGA) solution/ suspension and/ or colloidal silica suspension to enhance their resistance to moisture.
43. A method according to claim 20 or 26 wherein polyvinyl pyrrolidone is a spherical particle former.
44. A method according to any of claims 20-43 wherein the particles of the invention are used as they are produced or further processed via coating in a formulation in which are included.
45. A method according to claim 44 wherein the particles are milled.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB201914532A GB201914532D0 (en) | 2019-10-08 | 2019-10-08 | Lactose particles and method of production thereof |
| PCT/GB2020/052496 WO2021069901A1 (en) | 2019-10-08 | 2020-10-08 | Lactose particles and method of production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB202210051D0 GB202210051D0 (en) | 2022-08-24 |
| GB2606306A true GB2606306A (en) | 2022-11-02 |
Family
ID=68541484
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB201914532A Ceased GB201914532D0 (en) | 2019-10-08 | 2019-10-08 | Lactose particles and method of production thereof |
| GB2210051.5A Pending GB2606306A (en) | 2019-10-08 | 2020-10-08 | Lactose particles and method of production thereof |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB201914532A Ceased GB201914532D0 (en) | 2019-10-08 | 2019-10-08 | Lactose particles and method of production thereof |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP4138762A1 (en) |
| GB (2) | GB201914532D0 (en) |
| WO (1) | WO2021069901A1 (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004052334A2 (en) * | 2002-12-11 | 2004-06-24 | El Hassane Larhrib | Drug delivery particles and methods of treating particles to improve their drug delivery capabilities |
| WO2007045689A2 (en) * | 2005-10-21 | 2007-04-26 | Eratech S.R.L. | Inhalatory pharmaceutical compositions in form of dry powders, solutions or suspensions |
| WO2014143808A1 (en) * | 2013-03-15 | 2014-09-18 | Children's Medical Center Corporation | Hollow particles encapsulating a biological gas and methods of use |
-
2019
- 2019-10-08 GB GB201914532A patent/GB201914532D0/en not_active Ceased
-
2020
- 2020-10-08 GB GB2210051.5A patent/GB2606306A/en active Pending
- 2020-10-08 WO PCT/GB2020/052496 patent/WO2021069901A1/en unknown
- 2020-10-08 EP EP20793773.1A patent/EP4138762A1/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004052334A2 (en) * | 2002-12-11 | 2004-06-24 | El Hassane Larhrib | Drug delivery particles and methods of treating particles to improve their drug delivery capabilities |
| WO2007045689A2 (en) * | 2005-10-21 | 2007-04-26 | Eratech S.R.L. | Inhalatory pharmaceutical compositions in form of dry powders, solutions or suspensions |
| WO2014143808A1 (en) * | 2013-03-15 | 2014-09-18 | Children's Medical Center Corporation | Hollow particles encapsulating a biological gas and methods of use |
Non-Patent Citations (1)
| Title |
|---|
| EBRAHIMI AMIRALI ET AL,"Incorporation of acetaminophen as an active pharmaceutical ingredient into porous lactose",INTERNATIONAL JOURNAL OF PHARMACEUTICS, ELSEVIER, NL,(20160106), vol. 499, no. 1, doi:10.1016/J.IJPHARM.2016.01.007, ISSN 0378-5173, pages 217-227 1-3,8-19* figure 1 * * |
Also Published As
| Publication number | Publication date |
|---|---|
| GB202210051D0 (en) | 2022-08-24 |
| WO2021069901A1 (en) | 2021-04-15 |
| EP4138762A1 (en) | 2023-03-01 |
| GB201914532D0 (en) | 2019-11-20 |
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