Drug delivery systems comprising solid solutions of weakly basic drugs
Inventors
Venkatesh, Gopi M. • Boltri, Luigi • Colombo, Italo • Lai, Jin-Wang • Fabiani, Flavio • Mapelli, Luigi
Assignees
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Publication Number
US-12151028-B2
Publication Date
2024-11-26
Expiration Date
Abstract
The present invention is directed to pharmaceutical compositions and dosage forms comprising TPR beads, wherein said TPR beads comprise a solid dispersion of at least one active pharmaceutical ingredient in at least one solubility-enhancing polymer, and a TPR coating comprising a water insoluble polymer and an enteric polymer, wherein the active pharmaceutical ingredient comprises a weakly basic active pharmaceutical ingredient having a solubility of not more than 100 μg/mL at pH 6.8.
Core Innovation
The invention relates to timed pulsatile release (TPR) beads for weakly basic active pharmaceutical ingredients, where the active pharmaceutical ingredient has a solubility of not more than 100 μg/mL at pH 6.8. The TPR beads include a solid dispersion formed from the weakly basic active pharmaceutical ingredient in at least one solubility enhancing polymer, and the particles are formed as molecularly dispersed active pharmaceutical ingredient and solubility enhancing polymer.
The solid dispersion particles are coated with a TPR coating comprising a water insoluble polymer and an enteric polymer. The coating solution is formed by dissolving the water insoluble polymer and the enteric polymer in a pharmaceutically acceptable coating solvent, and the particles of the solid dispersion are coated with the TPR coating solution.
The resulting TPR beads provide a lag time of up to about 4 hours for the at least one active pharmaceutical ingredient. The pharmaceutical composition provides a therapeutically effective plasma concentration of the at least one active pharmaceutical ingredient over a period of at least 12 hours, and the document characterizes the solid dispersion and coating approach for delayed/sustained release behavior for weakly basic drugs.
Claims Coverage
The independent claim set recites 4 inventive features centered on a solid dispersion of a weakly basic active pharmaceutical ingredient and a TPR coating, with performance constraints of therapeutically effective plasma concentration over at least 12 hours and lag time up to about 4 hours. Dependent claims further refine polymer identity, compositional ratios, enteric loading, IR/TPR bead blending, and dosage-form integration into orally disintegrating tablets.
Weakly basic active pharmaceutical ingredient solid dispersion
A solid dispersion of at least one active pharmaceutical ingredient in at least one solubility enhancing polymer, wherein the at least one active pharmaceutical ingredient comprises a weakly basic active pharmaceutical ingredient having a solubility of not more than 100 μg/mL at pH 6.8, and wherein particles comprise molecularly dispersed at least one active pharmaceutical ingredient and at least one solubility-enhancing polymer.
TPR coating comprising water insoluble polymer and enteric polymer
A TPR coating comprising a water insoluble polymer and an enteric polymer, wherein the TPR beads provide a lag time of up to about 4 hours for the at least one active pharmaceutical ingredient.
Therapeutically effective plasma concentration over at least 12 hours
The composition provides a therapeutically effective plasma concentration of the at least one active pharmaceutical ingredient over a period of at least 12 hours.
Orally disintegrating tablet with rapidly dispersing microgranules
An orally disintegrating tablet is formed by granulating a disintegrant with a sugar alcohol and/or saccharide to form rapidly dispersing microgranules, mixing with TPR beads, and compressing the mixture into the tablet.
Across the claim set, the core inventive approach is a solid dispersion of a weakly basic active pharmaceutical ingredient in a solubility enhancing polymer followed by a TPR coating formed from a water insoluble polymer and an enteric polymer, configured to achieve therapeutically effective plasma concentration over at least 12 hours with a lag time up to about 4 hours. Dependent claims further refine the solubility-enhancing and coating polymer identities, specify API-to-polymer ratio and enteric coating loading, define an IR/TPR bead blend ratio, and extend the composition into orally disintegrating tablets using rapidly dispersing microgranules.
Stated Advantages
Improved and delayed/sustained release behavior for weakly basic active pharmaceutical ingredients.
Provides a lag time of up to about 4 hours.
Provides therapeutically effective plasma concentration over a period of at least 12 hours.
Documented Applications
Timed pulsatile release pharmaceutical composition using timed pulsatile release beads for weakly basic active pharmaceutical ingredients.
Orally disintegrating tablet formation incorporating rapidly dispersing microgranules mixed with TPR beads.
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