Modified release pharmaceutical formulations comprising deferiprone
Inventors
Pertile, Marisa • Gazzaniga, Andrea • Cerea, Matteo • CIRILLI, Micol
Assignees
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Publication Number
US-12016851-B2
Publication Date
2024-06-25
Expiration Date
Abstract
The disclosure is directed to pharmaceutical compositions for oral administration in form of coated tablets that exhibit modified release properties when administered as either whole or half tablets. In particular, the disclosure is directed to modified release tablets comprising deferiprone, said tablets being suitable for twice daily oral administration. The disclosure is also directed to methods of making and using the same.
Core Innovation
The invention relates to a delayed release tablet for twice a day oral administration that comprises a core and an enteric coating. The core comprises about 1000 mg deferiprone, with deferiprone present in an amount of about 85.0% to about 95.0% by weight of the tablet, and further includes a modifying release agent comprising a hydroxypropylmethylcellulose polymer having a viscosity of 100 cP, optionally together with a hydroxypropylmethylcellulose polymer having a viscosity of 4000 cP.
The modifying release agent is hydrophilic and HPMC-based, including defined viscosity grades and optional mixtures of the two viscosity grades, in an amount of about 5.0% to about 10.0% by weight of the tablet. The tablet includes a lubricant and/or glidant in an amount of about 0.2% to about 2.0% by weight of the tablet, and additional pharmaceutically acceptable excipients in an amount of about 0.0 to 5.0% by weight of the tablet.
The enteric coating provides delayed release behavior and is part of the overall gastroresistant coating system. The delayed release tablet is defined by dissolution performance measured by USP Apparatus Type I basket method, releasing less than about 20% of the deferiprone within 120 minutes at a pH of 1.2 and about 60% or more of the deferiprone within 180 minutes at a pH of 6.8 under the stated measurement conditions.
The disclosed concept emphasizes achieving a pH-independent and reproducible release profile across GI transit while controlling undesired burst on pH change, and includes maintaining dissolution and steady-state bioequivalence relative to Ferriprox® DR.
Claims Coverage
The provided text identifies two independent inventive feature groups: a delayed release tablet composition with defined materials and quantitative ranges, and a release profile suited for twice a day oral administration with specified USP dissolution limits.
Delayed release tablet with defined deferiprone and HPMC modifying release agent
A delayed release tablet comprising a core with about 1000 mg deferiprone, wherein the deferiprone is in an amount of about 85.0% to about 95.0% by weight of the tablet, and a modifying release agent comprising a hydroxypropylmethylcellulose polymer having a viscosity of 100 cP and optionally a hydroxypropylmethylcellulose polymer having a viscosity of 4000 cP in an amount of about 5.0% to about 10.0% by weight of the tablet, together with a lubricant and/or glidant and additional pharmaceutically acceptable excipients, and an enteric coating.
Twice a day oral suitability with specified USP release limits
The delayed release tablet is suitable for twice a day oral administration and wherein the tablet releases less than about 20% of the deferiprone within 120 minutes when measured by USP Apparatus Type I basket method at 100 rpm in 900 mL at 37° C. at a pH of 1.2 and about 60% or more of the deferiprone within 180 minutes when measured by USP Apparatus Type I basket method at 100 rpm in 900 mL at 37° C. at a pH of 6.8.
Overall, the claim coverage centers on a delayed release tablet formulation defined by high deferiprone loading, HPMC-based modifying release agent with optional 100 cP and 4000 cP viscosity grades, a lubricant and/or glidant and excipients within defined ranges, an enteric coating, and a release profile at pH 1.2 and pH 6.8 under USP Apparatus Type I conditions.
Stated Advantages
More reproducible pH-independent performance across GI transit.
Reduced undesired burst on pH change.
Maintaining dissolution and steady-state bioequivalence relative to Ferriprox® DR.
Documented Applications
Clinical use for iron overload diseases including thalassemia, sickle cell anemia, hemochromatosis/myelodysplasia, and transfusional iron overload, with twice-daily dosing.
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