Oral pharmaceutical composition comprising taste-masked N-acetylcysteine
Inventors
Becker, Karin • HAACK, DETLEV • SALAR BEHZADI, Sharareh • Zimmer, Andreas
Assignees
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Publication Number
US-9636307-B2
Publication Date
2017-05-02
Expiration Date
Abstract
The invention provides coated particles with taste-masked N-acetylcysteine. The particles comprise a core with the active ingredient and a coating comprising a triglyceride and a surfactant. The particles exhibit rapid drug release and a stable release profile. Moreover, the invention provides a hot-melt coating method for manufacturing such particles, and pharmaceutical compositions comprising the particles. The method allows the coating of core particles at moderate temperatures, thereby preventing the degradation of the thermolabile active ingredient.
Core Innovation
The invention is directed to a pharmaceutical composition comprising a coated particle having a core and a coating, wherein the core comprises N-acetylcysteine as the pharmacologically active ingredient. The coating comprises a triglyceride selected from the group consisting of glyceryl tripalmitate and glyceryl tristearate together with a non-ionic surfactant. The coated particle exhibits rapid release of the active ingredient.
The coating uses hot-melt triglyceride-based material intended to function in an oral taste-masked N-acetylcysteine formulation. The described coating includes a hot-melt triglyceride that is solid at room temperature, such as tripalmitin or tristearin, combined with a surfactant such as polysorbate 65. The surfactant is described as enabling coating at moderate temperatures to limit NAC degradation and to help stabilize the triglyceride polymorph.
The formulation is described as yielding rapid drug release and stable dissolution behavior during storage, with dissolution release reported after 15 minutes and storage follow-up showing no significant dissolution-profile change after about 3 months under specified temperature and relative humidity conditions.
Claims Coverage
The independent claim is directed to a coated-particle pharmaceutical composition of N-acetylcysteine with a specified triglyceride and a specified non-ionic surfactant, providing rapid release. The dependent claims refine identity and quantitative performance and stability limitations, including specific surfactant identity, coating composition ratios, coating weight fraction, dissolution release performance, and storage-related release-profile change.
Coated particle with N-acetylcysteine core and triglyceride/non-ionic surfactant coating enabling rapid release
A pharmaceutical composition comprising a coated particle comprising a core and a coating, wherein the core comprises N-acetylcysteine as the pharmacologically active ingredient, and wherein the coating comprises (i) a triglyceride selected from the group consisting of glyceryl tripalmitate and glyceryl tristearate, and (ii) a non-ionic surfactant selected from the group consisting of polysorbates, mono- and di-glycerides of fatty acids, propylene glycol esters, sucrose fatty acid esters, polyglycerol esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid ethers, and poloxamers; and wherein the coated particle exhibits rapid release of the active ingredient.
Triglyceride and polysorbate weight composition in the coating
The pharmaceutical composition wherein the coating comprises 70 to 90 wt.-% triglyceride and 10 to 30 wt.-% polysorbate.
Coating weight fraction on the coated particle
The pharmaceutical composition wherein the coating weight on a coated particle is 20 to 70 wt.% of the total weight of the coated particle.
Polysorbate 65 as the specified non-ionic surfactant
The pharmaceutical composition wherein the polysorbate component is polysorbate 65.
Rapid dissolution release in 0.1 N HCl
The pharmaceutical composition in which the coated particles, when tested by placing them in 900 mL of 0.1 N HCl and stirring in a USP paddle apparatus at 100 rpm, release at least about 95% of N-acetylcysteine equivalent to a 600 mg dose within 15 minutes.
No significant release-profile change after storage
The pharmaceutical composition whose drug release profile shows no significant change after 3 months of storage in sachets or glass bottles at 25°C/160% r.h., 30°C/65% r.h. or 40°C/75% r.h.
Across the independent claim and its dependents, the main claimed inventive structure is a coated particle with an N-acetylcysteine core and a coating containing a specific triglyceride (glyceryl tripalmitate or glyceryl tristearate) together with a defined non-ionic surfactant class. Further claimed refinements specify polysorbate/polysorbate 65, coating composition ratios and coating weight fraction, dissolution performance in 0.1 N HCl using a specified USP paddle setup, and stability showing no significant release-profile change after 3 months under stated storage conditions.
Stated Advantages
Rapid release of the active ingredient
Stable dissolution behavior during storage, with no significant dissolution-profile change after about 3 months under specified temperature and relative humidity conditions
Documented Applications
Oral taste-masked N-acetylcysteine formulations in solid oral dosage forms including dispersible/effervescent/direct-to-mouth granules and tablets
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