Granules of an active substance with double taste-masking technique, method for the production thereof, and orodispersible tablets containing same
Inventors
Herry, Catherine • Ailhas, Caroline
Assignees
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Publication Number
US-11872306-B2
Publication Date
2024-01-16
Expiration Date
Abstract
The present invention relates to granules of active ingredient with double taste masking, wherein the double taste masking is achieved by a hot-melt compound selected from waxes, hydrogenated vegetable oils, fatty acids, mono-, di- and triesters of fatty acids and of glycerol, triglycerides, glycerides, polyoxylglycerides, fatty alcohols, and mixtures thereof, and a thermoplastic polymer that is soluble at a pH less than or equal to 5. The invention also relates to the method for producing these granules and to orodispersible tablets containing these coated granules.
Core Innovation
The invention relates to a method for producing granules of active ingredient with double taste masking. The method performs two successive thermal granulation steps to form first granules and then final granules of the active ingredient, provided by the combination of a first compound and a second compound.
In step (a), the active ingredient is thermally granulated with a first compound at at least a melting temperature of the first compound. In step (b), the first granules are thermally granulated with a second compound at a temperature below step (a) and at least the glass thermoplastic temperature of the second compound.
The first compound comprises a hot-melt compound selected from waxes, hydrogenated vegetable oils, fatty acids, monoesters of fatty acids, diesters of fatty acids, triesters of fatty acids, monoesters of glycerol, diesters of glycerol, triesters of glycerol, triglycerides, glycerides, polyoxylglycerides, fatty acids, or mixtures of any of the foregoing hot-melt compounds. The second compound comprises a thermoplastic polymer soluble at a gastric pH less than or equal to 5, wherein the thermoplastic polymer is a cationic copolymer based on alkyl methacrylate and alkylamine methacrylate.
Each thermal granulation step is divided into three phases, comprising mixing at constant paddle and lump breaker speeds while increasing temperature, granulating at a stable temperature while increasing paddle and lump breaker speeds relative to the mixing step, and cooling by decreasing temperature while decreasing paddle and lump breaker speeds relative to the granulating step. The described process aims to enable controlled double taste masking granulation using sequential thermal processing.
Claims Coverage
The document includes one independent claim describing a two-step successive thermal granulation method with double taste masking, plus dependent claims that narrow and refine the independent method. The inventive features are primarily characterized by the two successive thermal steps using a hot-melt compound at its melting temperature and a gastric pH ≤ 5 soluble cationic thermoplastic polymer at least at its glass thermoplastic temperature, with each step carried out in three defined phases of mixing, granulating, and cooling.
Two successive thermal granulation steps for double taste masking
A method comprising thermally granulating an active ingredient with a first compound at at least a melting temperature of the first compound to form first granules, and then thermally granulating the first granules with a second compound at a temperature below the first step and at least the glass thermoplastic temperature of the second compound to form granules of the active ingredient with double taste masking provided by the combination of the first compound and the second compound.
Hot-melt first compound with thermoplastic second compound soluble at gastric pH ≤ 5
The first compound comprises a hot-melt compound selected from waxes, hydrogenated vegetable oils, fatty acids, monoesters of fatty acids, diesters of fatty acids, triesters of fatty acids, monoesters of glycerol, diesters of glycerol, triesters of glycerol, triglycerides, glycerides, polyoxylglycerides, fatty acids, or mixtures of any of the foregoing hot-melt compounds, and the second compound comprises a thermoplastic polymer that is soluble at a gastric pH less than or equal to 5, wherein the thermoplastic polymer is a cationic copolymer based on alkyl methacrylate and alkylamine methacrylate.
Three-phase thermal granulation within each step
Each thermal granulation step is divided into three phases: mixing at constant paddle and lump breaker speeds while increasing temperature; granulating at stable temperature while increasing paddle and lump breaker speeds relative to the mixing step; and cooling by decreasing temperature while decreasing paddle and lump breaker speeds relative to the granulating step.
Across the independent claim, the core claim coverage centers on forming intermediate granules by thermally granulating with a hot-melt compound at its melting temperature, followed by a second thermally granulation with a gastric pH ≤ 5 soluble cationic copolymer thermoplastic polymer at least at its glass thermoplastic temperature, with each thermal granulation step carried out in mixing, granulating, and cooling phases defined by paddle and lump breaker speed and temperature changes.
Stated Advantages
Provides double taste masking for very bitter actives.
Documented Applications
Pharmaceutical granules and orodispersible tablets intended for very bitter actives, including trazodone and trazodone hydrochloride, where double taste masking is desired.
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