Pharmaceutical composition containing phosphate binding polymer
Inventors
Karavas, Evangelos • Koutris, Efthimios • SAMARA, VASILIKI • Diakidou, Analia • Papanikolaou, Georgia • Mparmpalexis, Panagiotis
Assignees
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Publication Number
US-9849147-B2
Publication Date
2017-12-26
Expiration Date
Abstract
The present invention relates to a fast dissolving tablet comprising a therapeutically effective amount of a phosphate binding polymer, such as sevelamer or pharmaceutically acceptable salt or derivative thereof, that exhibit limited swelling in the oral cavity, has pleasant taste and mouth feel, high phosphate binding capacity with fast binding kinetics and require limited amount of water intake. A process for the preparation thereof is disclosed.
Core Innovation
The disclosed invention relates to a fast-disintegrating orally dispersible chewable, sublingual, or lozenge tablet pharmaceutical composition comprising sevelamer, including sevelamer HCl or carbonate, and pharmaceutically acceptable salts or derivatives, as an active ingredient and a pharmaceutically acceptable excipient system. The composition dissolves or disintegrates in the oral cavity and releases the active ingredient in less than 5 minutes, while providing limited oral swelling, pleasant taste and mouth feel, and reduced water intake.
A primary mechanism described is swelling suppression of sevelamer in the oral cavity. The excipient system forms a homogeneous mixture with the active ingredient via melt mixing, and in the homogeneous mixture the excipient directly bonds to the active ingredient and forms hydrogen bonds with amine groups of the active ingredient, thereby reducing swelling of the active ingredient in an oral cavity.
The disclosed compositions include excipients such as carnauba wax, glyceryl behenate, and glyceryl monostearate, and are produced using melt mixing and/or wet granulation or coating over sevelamer granules. FTIR spectra are used to support hydrogen bonding behavior, and in vitro phosphate binding comparisons with kinetic and binding-constant comparisons are described as comparable to marketed sevelamer products.
Claims Coverage
The partial content contains two independent claims. The claims define sevelamer-based orally dispersible, chewable, sublingual, or lozenge tablets that disintegrate or dissolve in the oral cavity within less than 5 minutes and reduce swelling by direct bonding and hydrogen bonding to sevelamer amine groups, with a distinction between melt-mixed excipients and a coating formed over active ingredient granules.
Melt-mixed excipient that hydrogen-bonds to sevelamer amine groups to reduce oral swelling
The pharmaceutically acceptable excipient forms a homogeneous mixture with sevelamer or a pharmaceutically acceptable salt or derivative via melt mixing, and in the homogeneous mixture the excipient bonds directly to the active ingredient and forms hydrogen bonds with amine groups of the active ingredient, thereby reducing swelling of the active ingredient in an oral cavity.
Orally dispersible, chewable, sublingual, or lozenge tablet disintegrating within 5 minutes
The pharmaceutical composition comprises a tablet that is orally dispersible, chewable, sublingual, or lozenge, wherein the pharmaceutical composition dissolves or disintegrates in the oral cavity releasing the active ingredient in less than 5 minutes.
Minimum excipient amount and specified wax or ester excipients
The pharmaceutically acceptable excipient comprises at least one of carnauba wax, glyceryl behenate, glyceryl monostearate, or mixtures thereof, and comprises an amount of at least 3% of the total weight of the tablet.
Coating formed over sevelamer granules with melt-mixed hydrogen-bonding excipients
The pharmaceutical composition comprises a coating formed over granules of the active ingredient, where the coating comprises a pharmaceutically acceptable excipient that comprises at least one of carnauba wax, glyceryl behenate, glyceryl monostearate, or mixtures thereof, wherein the excipient forms a homogeneous mixture with the active ingredient via melt mixing and in the homogeneous mixture the excipient bonds directly to the active ingredient and forms hydrogen bonds with amine groups of the active ingredient, thereby reducing swelling of the active ingredient in an oral cavity.
Across the independent claims, the inventive coverage centers on sevelamer tablets that rapidly dissolve or disintegrate in the oral cavity while reducing oral swelling through direct bonding and hydrogen bonding to sevelamer amine groups, using specified wax or ester excipients. The claims split the implementation between melt-mixed excipient within the tablet and an excipient coating formed over sevelamer granules.
Stated Advantages
Reduces swelling of the active ingredient in an oral cavity.
Dissolves or disintegrates in the oral cavity releasing the active ingredient in less than 5 minutes.
Provides high phosphate binding capacity and fast binding kinetics.
Reduced water intake.
Pleasant taste and mouth feel.
Documented Applications
Use as a phosphate binder via sevelamer released in the oral cavity from fast-dissolving or fast-disintegrating oral tablets in chewable, sublingual, or lozenge forms.
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