Oral preparation with controlled release
Inventors
Schlutermann, Burkhard • Kohlmeyer, Manfred
Assignees
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Publication Number
US-9005658-B2
Publication Date
2015-04-14
Expiration Date
Abstract
A pharmaceutical pellet is provided, comprising a spherical core containing the active substance with a smooth surface and a coating on the core, which controls pH-independent release of the active substance. With a pellet of this kind, the release of the active substance may follow a profile with a lag-phase from 60 minutes to 840 minutes, where during the lag-phase a proportion of 5 wt. % or less of the active substance is released. Furthermore, the active substance may be released from the pellet with a profile such that, after the lag-phase, the release of the active substance is between 3 and 25 wt. % per hour. The active substance is a metoprolol salt.
Core Innovation
The invention relates to a pharmaceutical pellet for oral controlled release, comprising a spherical core having a smooth surface. The spherical core comprises a core seed free of metoprolol salt and comprising at least one carbohydrate, and a layer comprising a metoprolol salt formed on top of the core seed. The pellet further comprises a coating comprising polyvinyl acetate.
The polyvinyl acetate coating is formed on the spherical core in an amount of 40–60 wt. % based on the weight of the spherical core. The coating is configured to control pH-independent release of the active substance. The described spherical core smoothness and surface roughness criteria are used to support reliable coating and reproducible release behavior.
The release behavior described includes a lag phase of 60–840 min, during which ≤5 wt% of the active substance is released. After the lag phase, the release rate is described as 3–25 wt% per hour. The disclosed pellet geometry/roughness and coating amount variations (45/50/60 wt%) are linked to the resulting release trends.
Claims Coverage
The independent claim provides the overall composition of a metoprolol-salt oral controlled-release pellet with a smooth spherical carbohydrate-containing core, a metoprolol-salt layer, and a polyvinyl acetate coating that controls pH-independent release. The independent claim coverage is refined by dependent claims that add quantitative release-profile constraints and structural/particle parameters.
Spherical core with smooth surface and metoprolol-salt layer
A pharmaceutical pellet having a spherical core with a smooth surface, where the core seed is free of metoprolol salt and comprises at least one carbohydrate, and a layer comprising a metoprolol salt as an active substance is formed on top of the core seed.
Polyvinyl acetate coating for pH-independent release
A coating comprising polyvinyl acetate, formed on the spherical core in an amount of 40–60 wt.% based on the weight of the spherical core, wherein the coating controls pH-independent release of the active substance.
Lag phase release profile
The pellet produces an active substance release profile with a lag phase of 60 to 840 minutes, during which 5 wt.% or less of the active substance is released.
Post-lag release rate range
The pellet produces, after a lag phase, an active substance release rate between 3 and 25 wt.% per hour.
Core diameter range
A spherical core having a diameter between 0.2 and 2 mm.
Core surface mean roughness limit
A spherical core having a mean roughness of less than 10 μm.
Compression step with disrupted pellets
A method includes a compression step in which disrupting some of the pellets shortens the lag-phase for release of the active substance from the tablet compared with the pellets.
Overall claim coverage centers on a spherical smooth-surface carbohydrate-containing core seed free of metoprolol salt, a metoprolol-salt active substance layer formed on top of the core seed, and a polyvinyl acetate coating (40–60 wt.%) that controls pH-independent release, with dependent claim refinements defining quantitative lag-phase and post-lag release-rate ranges, and structural constraints such as core diameter and mean roughness, and further narrowing to tablet compression with disrupted pellets that alters lag-phase behavior.
Stated Advantages
Controls pH-independent release of the active substance.
Enables a described oral controlled release profile with a lag phase and a defined post-lag release rate range.
Supports reliable coating and reproducible release based on smooth pellet geometry/roughness.
Documented Applications
Oral controlled release using the described metoprolol-salt pharmaceutical pellets, including release behavior characterized by a lag phase and post-lag release rate.
Tablet production involving a compression step in which disrupting some of the pellets affects lag-phase release from the tablet.
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