Solid dispersions
Inventors
Chen, Zhengming • Chen, Xiaoming • Halloran, Kevin
Assignees
Publication Number
US-10596118-B2
Publication Date
2020-03-24
Expiration Date
2036-03-10
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Abstract
An ospemifene solid dispersion for enhancing solubility and bioavailability, and methods of preparation thereof are disclosed. The solid dispersion comprises an active pharmaceutical ingredient, such as ospemifene, and a hydfophilie carrier, such as copovidone, hypromellose acetate succinate, polyvinylpyrrolidine, a polyvinylpyrrolidine/vinyl acetate co-polymer, hydroxyl propyl methylcellulose, hypromellose acetate succinate, a Eudragit® compound, hydroxypropylcellulose, a polyvinyl caprolactam-polyvinyl acetate polyethylene glycol graft co-polymer, hydroxypropyl methylcellulose phthalate, and mixtures thereof, and optionally a surfactant The ospemifene solid, dispersions can be used in methods of treating a symptom related, to menopause, such as vaginal dryness or sexual dysfunction, or in methods of treating osteoporosis.
Core Innovation
The invention provides a solid dispersion composition containing ospemifene and a hydrophilic carrier, which enhances the solubility and bioavailability of ospemifene, a poorly water-soluble drug. The hydrophilic carrier may include materials such as copovidone, polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate copolymer, hydroxyl propyl methylcellulose, hypromellose acetate succinate, methacrylic acid copolymer, hydroxypropylcellulose, polyvinyl caprolactam-polyvinyl acetate polyethylene glycol graft copolymer, hydroxypropyl methylcellulose phthalate, and mixtures thereof.
The problem addressed is the poor water solubility and low oral bioavailability of many new drug candidates, particularly ospemifene, which hinders their effective absorption and requires higher doses for therapeutic effect. Existing solid dispersion technologies can improve solubility but suffer from limitations such as complex preparation methods, reproducibility issues, challenges in dosage form formulation, scale-up complications, and stability concerns of the drug and carrier.
This patent discloses compositions and methods for preparing solid dispersions of ospemifene with selected hydrophilic carriers, optionally including surfactants, via melting or solvent evaporation processes. The resulting compositions can be formulated into various pharmaceutical dosage forms, promoting enhanced dissolution and absorption characteristics. The invention also details specific embodiments with defined ratios of ospemifene to carrier and optional surfactant to carrier, providing improved performance in terms of solubility and stability compared to previous formulations.
Claims Coverage
There are two main independent claim inventive features described in the claims.
Solid dispersion of ospemifene and specified hydrophilic carrier
A solid dispersion composition in solid state comprising ospemifene and a hydrophilic carrier selected from copovidone, polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate copolymer, hydroxyl propyl methylcellulose, hypromellose acetate succinate, methacrylic acid copolymer, hydroxypropylcellulose, polyvinyl caprolactam-polyvinyl acetate polyethylene glycol graft copolymer, hydroxypropyl methylcellulose phthalate, and mixtures thereof, with the solid dispersion being in a solid state.
Pharmaceutical composition comprising the solid dispersion and a pharmaceutically acceptable excipient
A pharmaceutical composition containing the above ospemifene solid dispersion and at least one pharmaceutically acceptable excipient. The composition may be provided in a dosage form, may include specific excipients such as glidants, dispersants, enteric coatings, lubricants, binders, buffering agents, and may have characteristic ratios of hydrophilic carrier to surfactant.
The claims cover solid dispersions of ospemifene with specific hydrophilic carriers and pharmaceutical compositions containing these dispersions with defined excipients and characteristics, targeting the improvement of solubility and bioavailability of ospemifene.
Stated Advantages
The solid dispersion forms significantly enhance the solubility and dissolution of ospemifene in aqueous media, including up to several hundred-fold increases in certain formulations.
These compositions can increase the bioavailability of ospemifene, potentially allowing for effective treatment with lower daily dosages than traditional formulations.
Formulations may show equivalent or greater bioavailability in the fasted state compared to the fed state, reducing the need for administration with food.
The use of specific carriers and preparation methods results in compositions with improved physical stability and chemical compatibility.
Enhanced solubility and stability allow for more flexible and varied dosage forms, enabling improved patient compliance and administration options.
Documented Applications
Methods of treating symptoms related to menopause, including vaginal dryness and sexual dysfunction, using the ospemifene solid dispersion.
Methods of treating osteoporosis using the ospemifene solid dispersion.
Pharmaceutical dosage forms including tablets, capsules, powders, granules, films, rings, and gels formulated with the ospemifene solid dispersion.
Use in oral administration for increased bioavailability and improved therapeutic effect of ospemifene.
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