Crystalline microspheres and the process of manufacturing the same
Inventors
Propst, Cecil W. • Meadows, Marc W. • TODD, Michael S.
Assignees
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Publication Number
US-10245232-B2
Publication Date
2019-04-02
Expiration Date
Abstract
Microspheres comprising a core material, wherein the microspheres have a circularity greater than 0.95 and an aspect ratio greater than 0.95, and methods of manufacturing the same. The microspheres may be 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 disclosure describes crystalline, perfectly spherical pharmaceutical microspheres having quantified morphology and structure metrics. The microspheres are characterized by circularity greater than 0.95 and an aspect ratio of shortest diameter to longest diameter greater than 0.95, together with high solidity, convexity, and absence of internal voids or porosity.
The pharmaceutical microspheres are also characterized by performance properties related to moisture behavior. The microspheres are described with low hygroscopicity, low moisture gain, and low moisture content, including moisture gain of less than 1.0% at 90% relative humidity. Characterization is described using Karl Fischer moisture and Dynamic Vapor Sorption, alongside crystallinity and density measurements.
The disclosure emphasizes crystalline core materials and density, including examples of alpha mannitol and reported skeletal density values around 1.4595 to 1.4651 g/cc. The microspheres can be very small, down to about 10 μm, and highly crystalline, with analytical characterization including DSC crystallinity or melting behavior, helium pycnometry skeletal density, microscopy, and image analysis.
Claims Coverage
The independent claim coverage is directed to a microsphere defined by a combination of morphology metrics, skeletal density, and moisture gain, with four core inventive features explicitly present in the provided material. Dependent claims refine the microsphere with additional constraints on particle size, moisture content, composition, and absence of internal voids.
Spherical morphology with high circularity and aspect ratio
The microsphere has a circularity greater than 0.95 and an aspect ratio of shortest diameter to longest diameter greater than 0.95.
Skeletal density within a defined range
The microsphere has a skeletal density from about 1.4595 g/cc to about 1.4651 g/cc.
Low moisture gain at high relative humidity
The microsphere has a moisture gain of less than 1.0% at 90% relative humidity.
Mean particle size within a defined range
The microsphere has a mean particle size ranging from about 10 μm to about 500 μm.
Moisture content threshold
The microsphere has a moisture content of 0.5% or less.
Single core material as mannitol
The microsphere has a single core material that is mannitol.
No internal voids
The microsphere has no internal voids.
Composition including an active pharmaceutical ingredient
The composition further includes an active pharmaceutical ingredient.
Overall claim coverage is anchored on microspheres with tightly defined spherical morphology, defined skeletal density, and low moisture gain at 90% relative humidity, with further refinements such as particle size range, moisture content, mannitol single-core specification, and absence of internal voids. Coverage also extends to compositions that include the microspheres and an active pharmaceutical ingredient.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Sustained/modified-release bead manufacture using the microspheres.
Mini-tablet excipient use.
API carrier dispersions.
Compositions containing APIs, including potential API loading inside or on the outside.
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