Pharmaceutical composition for oral administration comprising taxane
Inventors
Lee, In-Hyun • Son, Min-hee • Park, Yeong-Taek • LEE, Seul-Ae • LEE, Han-Koo
Assignees
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Publication Number
US-11116744-B2
Publication Date
2021-09-14
Expiration Date
Abstract
Provided is a pharmaceutical composition for oral administration, including (a) a taxane, (b) a medium chain triglyceride, (c) an oleoyl glycerol complex having 30 to 65% by weight of monooleoyl glycerol contents; 15 to 50% by weight of dioleoyl glycerol contents; and 2 to 20% by weight of trioleoyl glycerol contents, (d) a surfactant, and optionally (e) polyoxyl glyceryl fatty acid ester and a process for preparing the same.
Core Innovation
The invention relates to an oral taxane pharmaceutical composition comprising paclitaxel or docetaxel, a medium chain triglyceride, and an oleoyl glycerol complex. The oleoyl glycerol complex is present as monooleoyl glycerol, dioleoyl glycerol, and trioleoyl glycerol in defined weight-percent ranges, together with a surfactant and polyoxyl glyceryl fatty acid ester.
The composition is formulated to be in a clear solution form at room temperature. Conventional oral taxane formulations based on monoolein require heating or melting at about 50°C, whereas the disclosed composition changes to a clear solution form when allowed to stand at room temperature after being stored at 4°C.
The disclosed formulations are precipitate-free and allow formation of clear high-concentration solutions suitable for soft capsules. Example formulations and comparative examples demonstrate clear high-concentration solutions, stability of soft capsules, and pharmacokinetic results in mice.
The reported outcome is an improvement in in vivo absorption rate versus a monoolein-based conventional formulation, alongside room-temperature clarity.
Claims Coverage
The independent claim is clm-00001, which specifies a pharmaceutical composition for oral administration with five essential components quantified by weight-percent ranges and functional clarity requirements. The main inventive features are expressed through the combined selection and defined proportions of a taxane, a medium chain triglyceride, a defined oleoyl glycerol complex, a selected surfactant, and a polyoxyl glyceryl fatty acid ester, together with room-temperature clarity and post-cold-storage behavior.
Clear-room-temperature oral taxane composition with defined oleoyl glycerol complex
A pharmaceutical composition for oral administration consisting essentially of paclitaxel or docetaxel at 4 to 40% by weight, a medium chain triglyceride at 10 to 30% by weight, and an oleoyl glycerol complex at 30 to 70% by weight having 30 to 65% by weight of monooleoyl glycerol contents, 15 to 50% by weight of dioleoyl glycerol contents, and 2 to 20% by weight of trioleoyl glycerol contents.
Surfactant selection combined with polyoxyl glyceryl fatty acid ester for room-temperature clarity
The composition further includes a surfactant selected from polyoxyethylene-polypropylene block copolymer, sorbitan ester, polyoxyethylene sorbitan, and polyoxyethylene ether at 5 to 30% by weight, and polyoxyl glyceryl fatty acid ester at 10 to 30% by weight.
Room-temperature clear solution and post-4°C standing clarity
The pharmaceutical composition is in a clear solution form at room temperature, and is changed to a clear solution form when allowed to stand at room temperature after being stored at 4°C.
Overall, the independent claim focuses on an oral taxane formulation that combines a medium chain triglyceride with an oleoyl glycerol complex defined by mono-/di-/triglycerol weight-percent ranges, together with a selected surfactant and polyoxyl glyceryl fatty acid ester, while requiring the composition to be clear at room temperature and to become clear after cold storage followed by standing.
Stated Advantages
Clear solution at room temperature without heating or melting.
Improved in vivo absorption rate versus a monoolein-based conventional formulation.
Formation of precipitate-free clear high-concentration solutions suitable for soft capsules.
Clear solution maintenance after storage at 4°C followed by standing at room temperature.
Documented Applications
Oral administration of taxane pharmaceutical compositions comprising paclitaxel or docetaxel.
Soft capsules containing precipitate-free clear high-concentration solutions.
Pharmacokinetic evaluation in mice using UPLC-MS/MS and HPLC.
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