Crystalline microspheres and the process of manufacturing the same
Inventors
Propst, Cecil W. • Meadows, Marc W. • TODD, Michael S.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9089487-B2
Publication Date
2015-07-28
Expiration Date
Abstract
The present invention relates to microspheres comprising a core material, wherein the microsphere is perfectly spherical and has a moisture content less than 1%, and the method of manufacturing the same. The present invention is useful in the manufacture of sustained and modified release active pharmaceutical ingredient (API) microspheres, as a free flowing excipient for mini-tablets and in the manufacture of API dispersions.
Core Innovation
The invention relates to crystalline, perfectly spherical pharmaceutical microspheres having a core material. The microspheres are characterized by very low moisture content, and their hygroscopicity/gain is assessed using Karl Fisher or Dynamic Vapor Sorption (DVS). Moisture is also measured by loss on drying, supporting that the microspheres maintain a moisture level of less than about 1%.
The microspheres further exhibit high geometric quality, including circularity, aspect ratio, solidity, and convexity values consistent with ISO 9276-6. They lack porosity and internal voids, as shown by helium pycnometry skeletal density and SEM cross-sections. Surface roughness and ridges are described as being low, with ridge and peak-to-valley values reported.
The microspheres are also described as having high crystallinity, including DSC results indicating alpha mannitol for mannitol-based microspheres, with comparable DSC results for other described polyols. The document reports that the crystalline structure is associated with the low-moisture, non-porous, perfectly spherical form, and provides manufacturing approaches including prilling/spray chilling, spin-disc droplet formation, and a sonic-nozzle spherisator.
Claims Coverage
Two independent claims are identified. Both independent claims define microspheres by core material plus quantitative shape metrics (circularity and aspect ratio), and Claim 24 additionally defines a moisture content constraint.
Microsphere with high circularity, high aspect ratio, and lack of porosity
A microsphere comprising a core material, wherein the microsphere has a circularity greater than 0.95, an aspect ratio greater than 0.95, and lacks porosity.
Microsphere with high circularity, high aspect ratio, and low moisture content
A microsphere comprising a core material, wherein the microsphere has a circularity greater than 0.95, an aspect ratio greater than 0.95, and a moisture content of 0.5% or less.
The independent claim coverage focuses on microspheres with a core material that meet specified shape metrics (circularity > 0.95 and aspect ratio > 0.95), with Claim 1 additionally requiring lack of porosity and Claim 24 additionally requiring moisture content of 0.5% or less.
Stated Advantages
Very low moisture content, including hygroscopicity/gain behavior assessed by Karl Fisher or DVS.
High geometric quality including circularity, aspect ratio, solidity, and convexity (ISO 9276-6).
Lack of porosity and internal voids as indicated by helium pycnometry skeletal density and SEM cross-sections.
Smooth surface roughness with low ridge/peak-to-valley values.
High crystallinity indicated by DSC (e.g., alpha mannitol for mannitol-based microspheres).
Documented Applications
Sustained and modified release beads.
API carriers for tablet/mini-tablets.
API dispersions.
Layering and lyophilization.
Placebo beads.
Interested in licensing this patent?