Extended-release oral dosage forms for poorly soluble amine drugs
Inventors
Zu, Yanming • GORUKANTI, Sudhir • Ahmed, Salah Uddin
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9011912-B2
Publication Date
2015-04-21
Expiration Date
Abstract
Oral dosage forms for poorly soluble amine drugs are provided. Such dosage forms include an ionizable compound such as an organic acid, an amphiphilic polymer and a release rate-controlling membrane. Such dosage forms allow for the consistent release of the active agent in both gastric pH conditions and in the intestine. Methods of making such dosage forms are also provided.
Core Innovation
The invention provides an extended-release oral dosage form for poorly soluble amine compounds. The dosage form includes a core having an ionizable compound, where the ionizable compound is an organic acid selected from citric acid, maleic acid and combinations thereof, and a barrier layer coating the core.
The dosage form further includes a mantle of a matrix having a poorly soluble amine compound and at least one amphiphilic polymer. The amphiphilic polymer is selected from polyethylene glycol 6000/vinylcaprolactam/vinyl acetate 13/57/30, d-α-tocopheryl polyethyleneglycol 1000 succinate (Vitamin E-TPGS), and combinations thereof, and the ionizable compound and the amphiphilic polymer are used in amounts sufficient to provide synergistic solubility effect.
The extended-release oral dosage form additionally includes a release-rate controlling layer coating the mantle. In one claim set, the release-rate controlling layer is configured as a release-rate controlling membrane covering the core, selected from hydrophobic polymer, enteric polymer, hydrophilic polymer, plasticizer and combinations thereof.
Claims Coverage
The patent includes two independent claims that cover extended-release oral dosage forms for poorly soluble amine compounds. Across the independent claims, three inventive feature themes recur: an organic-acid ionizable core with barrier layer, a mantle matrix combining the poorly soluble amine with specified amphiphilic polymer, and a release-rate controlling layer or membrane.
Organic acid ionizable core with barrier layer
An ionizable compound in the core is an organic acid selected from citric acid, maleic acid and combinations thereof, and a barrier layer coatings the core.
Mantle matrix combining poorly soluble amine and specified amphiphilic polymer
A mantle of a matrix having a poorly soluble amine compound and at least one amphiphilic polymer, wherein the amphiphilic polymer is selected from polyethylene glycol 6000/vinylcaprolactam/vinyl acetate 13/57/30, d-α-tocopheryl polyethyleneglycol 1000 succinate (Vitamin E-TPGS), and combinations thereof.
Synergistic solubility effect from ionizable compound and amphiphilic polymer
The ionizable compound and the amphiphilic polymer are in amounts sufficient to provide synergistic solubility effect.
Release-rate controlling layer or membrane
A release-rate controlling layer coating the mantle, or a release-rate controlling membrane covering the core, selected from hydrophobic polymer, enteric polymer, hydrophilic polymer, plasticizer and combinations thereof.
Overall claim coverage centers on an extended-release oral dosage form architecture with an organic-acid ionizable core and barrier layer, a mantle matrix combining the poorly soluble amine with specified amphiphilic polymer, and a release-rate controlling layer or core-covering membrane.
Stated Advantages
Synergistic solubility effect.
Improved extended-release oral dosage form performance for poorly soluble amine compounds as supported by increased solubility of paliperidone when combining citric acid and SoluPlus® versus citric acid alone [procedural detail omitted for safety].
Documented Applications
Extended-release oral dosage forms for poorly soluble amine compounds, including paliperidone and donepezil (HCl) as representative examples.
Interested in licensing this patent?