Pharmaceutical composition for oral administration comprising high concentration taxane
Inventors
Lee, In-Hyun • Son, Min-hee • Park, Yeong-Taek • LEE, Han-Koo
Assignees
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Publication Number
US-10987335-B2
Publication Date
2021-04-27
Expiration Date
Abstract
The present invention provides a pharmaceutical composition for oral administration, consisting essentially of (a) 4 to 40% by weight of a taxane, (b) 10 to 40% by weight of polyoxyl glyceryl fatty acid ester, (c) 30 to 70% by weight of monooleoyl glycerol or 30 to 70% by weight of 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, and (d) 5 to 30% by weight of a surfactant and a process for preparing the same.
Core Innovation
The invention provides an oral pharmaceutical composition comprising paclitaxel or docetaxel, a polyoxyl glyceryl fatty acid ester selected from caprylocaproyl polyoxyl glyceride, lauroyl polyoxyl glyceride, and stearoyl polyoxyl glyceride, and monooleoyl glycerol or an oleoyl glycerol complex having defined monooleoyl, dioleoyl, and trioleoyl glycerol contents. The composition further includes polyoxyethylene (80) sorbitan monooleate and is in the form of a clear solution.
The described approach uses polyoxyl glyceryl fatty acid ester in place of medium-chain triglyceride to form a clear, precipitate-free high drug concentration solution. The formulation maintains solution form at room temperature using an oleoyl glycerol complex with specified monooleoyl/dioleoyl/trioleoyl glycerol proportions.
The document states that the oral taxane formulation improves in vivo absorption rate versus monoolein-based formulations and reports pharmacokinetic parameters including early absorption and higher Cmax and AUC in mice. It also describes formulation and process overviews, precipitation observations, and stability observations including no leaks and no appearance changes over 1–6 months.
Claims Coverage
The independent claims are clm-00001, clm-00006, and clm-00007. Across these claims, there are three main inventive features, covering a specific oral clear-solution composition and two related processes for preparing that clear-solution composition.
Clear oral taxane composition with polyoxyl glyceryl fatty acid ester and oleoyl glycerol complex
A pharmaceutical composition for oral administration consisting essentially of paclitaxel or docetaxel, polyoxyl glyceryl fatty acid ester selected from caprylocaproyl polyoxyl glyceride, lauroyl polyoxyl glyceride, and stearoyl polyoxyl glyceride, monooleoyl glycerol or an oleoyl glycerol complex having specified monooleoyl, dioleoyl, and trioleoyl glycerol contents, and polyoxyethylene (80) sorbitan monooleate, wherein the pharmaceutical composition is in the form of a clear solution.
Process of dissolving and mixing to obtain a clear oral taxane solution
A process for preparing a pharmaceutical composition for oral administration comprising dissolving paclitaxel or docetaxel and polyoxyl glyceryl fatty acid ester in an organic solvent; removing the organic solvent followed by mixing monooleoyl glycerol or an oleoyl glycerol complex and polyoxyethylene (80) sorbitan monooleate therewith to form a solution; optionally filling the solution in a capsule, wherein the pharmaceutical composition is in the form of a clear solution.
Alternative process order for preparing a clear oral taxane solution
A process for preparing a pharmaceutical composition for oral administration comprising dissolving paclitaxel or docetaxel, polyoxyl glyceryl fatty acid ester, monooleoyl glycerol or an oleoyl glycerol complex, and polyoxyethylene (80) sorbitan monooleate in an organic solvent; removing the organic solvent; and optionally filling the solution in a capsule, wherein the pharmaceutical composition is in the form of a clear solution.
The independent claims collectively require a clear-solution oral formulation containing paclitaxel or docetaxel with defined components of polyoxyl glyceryl fatty acid ester and monooleoyl/oleoyl glycerol complex, plus polyoxyethylene (80) sorbitan monooleate, and they cover processes for preparing such clear solutions using organic solvent dissolution and solvent removal with optional capsule filling.
Stated Advantages
Clear, precipitate-free high-concentration solution at room temperature.
Improved in vivo absorption rate versus monoolein-based formulations.
Stability with no leaks and no appearance changes over 1–6 months.
Pharmacokinetic improvement with early absorption and higher Cmax and AUC in mice.
Documented Applications
Oral administration of paclitaxel or docetaxel using the stated pharmaceutical composition in the form of a clear solution.
Preparation of the oral pharmaceutical composition by dissolving, removing organic solvent, and optionally filling in a capsule.
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