Functional polymer film-coated particle having high drug content, tablet containing same, and methods for production thereof
Inventors
Hayashida, Tomohiro • Yamazaki, Junji • Nakano, Yoshio • HIZAKI, Masaya • Kinoshita, Naotoshi
Assignees
Powerex Corp • Powrex KK • Zensei Pharmaceutical Industries Co Ltd
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Publication Number
US-9693965-B2
Publication Date
2017-07-04
Expiration Date
Abstract
Provided are functional drug-containing particles which can be compressed into tablets and in particular, to orally disintegrating tablets by employing any of a dry molding method, a wet molding method, or a humidifying drying method. The functional drug-containing particles comprise substantially spherical drug-containing particles essentially including drug and a binder, the functional drug-containing particles including a functional polymer film selected from the group consisting of an enteric film, a release control film, and a bitter taste masking film, an average particle diameter of said functional drug-containing particles being 400 μm or less, a particle diameter ratio D90/D10 of the functional drug-containing particles with respect to particle size distribution calculated on a volumetric basis being 1.65 or more, or a coefficient of variation in particle diameters being 24% or more.
Core Innovation
The invention relates to high-drug-content functional drug-containing particles for compression-moldable orally disintegrating tablets. The functional drug-containing particles are substantially spherical and essentially include drug particles and a binder, and the particles are coated with a film of a functional polymer selected from an enteric polymer, a release control polymer, and a bitter taste masking polymer.
The functional drug-containing particles have an average particle diameter of 400 μm or less. The substantially spherical drug-containing particles are manufactured from a solution of the binder including dissolved or suspended drug by using a spray drying fluidized bed granulation apparatus.
The document further links the coated functional drug-containing particles to compression molding and orally disintegrating tablet performance. It describes tablet formulations and manufacturing approaches that achieve target tablet hardness and intraoral disintegration, using functional polymer-coated particles to reduce the need for excipients.
Additional refinements describe particle size distribution constraints and tablet composition and mechanical thresholds, together with tablet manufacturing routes that include humidifying and drying steps and the use of amorphous-forming saccharides or sugar alcohols, in connection with compression-molded tablets made from the functional drug-containing particles.
Claims Coverage
The claim set centers on functional drug-containing particles with specific particle shape, size, composition, and manufacturing by spray drying fluidized bed granulation apparatus, followed by coating with a functional polymer film. Dependent claims further add inventive features related to particle size distribution, quantitative tablet composition and mechanical thresholds, specific coating and film selections, and specific tablet manufacturing features.
Functional drug-containing particles with functional polymer film and <=400 μm average diameter
Functional drug-containing particles essentially including drug particles and a binder, coated with a film of a functional polymer selected from an enteric polymer, a release control polymer, and a bitter taste masking polymer, wherein the functional drug-containing particles have an average particle diameter of 400 μm or less.
Spray drying fluidized bed granulation from binder solution including dissolved or suspended drug
The substantially spherical drug-containing particles are manufactured from a solution of the binder including dissolved or suspended drug by using a spray drying fluidized bed granulation apparatus.
Broad particle size distribution by D90/D10 or diameter CV constraint
The functional drug-containing particles have either a broad particle size distribution with a volumetric particle diameter ratio D90/D10 of 1.65 or more, or a particle diameter coefficient of variation of 24% or more.
Tablet with at least 50% by weight functional drug-containing particles and hardness at least 40 N
A tablet comprises the functional drug-containing particles and an auxiliary component, where the content of the functional drug-containing particles is at least 50% by weight and the tablet has hardness of at least 40 N.
Tablet manufacturing using amorphous-capable saccharide or sugar alcohol conversion with compression molding
A method coats the functional drug-containing particles with a saccharide or sugar alcohol capable of becoming amorphous, then compression molds the coated substance at a pressure of 5 kN/cm2 or less and humidifies and dries the molded tablet to convert the saccharide from an amorphous state to a crystalline state.
Valacyclovir hydrochloride and bitter taste masking film as functional film selection
The functional drug-containing particles use valacyclovir hydrochloride as the drug and employ a bitter taste masking film as the functional film.
Overall, the claims are directed to substantially spherical functional drug-containing particles with an average particle diameter of 400 μm or less, made by spray drying fluidized bed granulation from a binder solution containing dissolved or suspended drug, and coated with a film of an enteric polymer, a release control polymer, or a bitter taste masking polymer. Dependent features add particle size distribution constraints, tablet composition and mechanical thresholds, and saccharide or sugar-alcohol and film selections in connection with compression-molded tablets.
Stated Advantages
Improved moldability enabling tablets with reduced excipient need.
Achieving tablet hardness targets and intraoral disintegration targets.
Low-pressure tablet manufacture approaches are described, including compression molding routes and drying and humidifying related routes.
Documented Applications
Compression-moldable orally disintegrating tablets using high-drug-content functional drug-containing particles coated with functional polymer films.
Tablet formulations including ambroxol hydrochloride and valacyclovir hydrochloride using the functional drug-containing particles.
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