EP-4740939-A1 - COATING SOLUTIONS WITH IMPROVED COVERING AND WHITENING EFFECT

EP4740939A1EP 4740939 A1EP4740939 A1EP 4740939A1EP-4740939-A1

Abstract

The invention relates to coating solutions comprising a polyol, a polymer, and a solvent, wherein the polyol is mannitol or xylitol and the polymer is an aqueous soluble polymer or a cellulose based polymer, and the use of said coating solutions in the coating of medicaments. The invention further relates to a method for coating a medicament and the use of mannitol in a coating solution for medicaments.

Inventors

The designation of the inventor has not yet been filed

Assignees

Merck Patent GmbH

Dates

Publication Date: 20260513
Application Date: 20241108

Claims (15)

A coating solution, comprising - a polyol, - a polymer, - a solvent, and, - optionally, a plasticizer; wherein the polyol is mannitol or xylitol and the polymer is an aqueous soluble polymer or a cellulose based polymer.
The coating solution of claim 1, wherein the aqueous soluble polymer is selected from the group consisting of polyvinyl alcohol (PVA), copovidone vinylpyrrolidone-vinyl acetate copolymers (PVP-VA), polyvinyl pyrrolidone, methacrylic acid copolymers, and shellac; and/or wherein the cellulose based polymer is selected from the group comprising methylcellulose, hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxyethyl methyl cellulose (HEMC), ethylcellulose (EC), and cellulose acetate phthalate.
The coating solution of any of claims 1 to 2, wherein the polyol is mannitol and the polymer is PVA, the w/w% ratio of mannitol to PVA being preferably between about 40 : 60, preferably,50 : 50 and more preferably 85:15.
The coating solution of any of claims 1 to 3, wherein the coating solution comprises mannitol at a w/w% concentration between 5 and 40%, preferably between 7.5% and 15%.
The coating solution of any of claims 1 to 4, further comprising an anti-tacking agent, wherein the anti-tacking agent is preferably selected from the group consisting of talcum, magnesium stearate, microcrystalline cellulose, glyceryl monostearate, stearic acid, kaolin and colloidal silicon dioxide.
The coating solution of any of claims 1 to 5, wherein the plasticizer is selected from the group comprising triethylcitrate, triacetin, glycerol, and polyethylene glycols of molecular weights between 600 and 6000 Da, preferably between 1000 and 3000 Da.
The coating solution of any of claims 1 to 6, wherein the solvent is a water-based solvent, an alcohol, a ketone, an ester or a chlorinated hydrocarbon or a mix thereof.
The coating solution of any of claims 1 to 7, wherein the color distribution values of the coating solution according to L*a* b* values of CIELAB color space are L* > 90, preferably L* > 95, -5 < a* < 10, preferably -2 < a* < 5, preferably -1 < a* < 1, more preferably a* = 0, and -5 < b* < 10, preferably -2 < b* < 5, preferably -1 < b* < 1, more preferably b* = 0, as measured by color card trials.
Use of the coating solution of any of claims 1 to 8, as a coating of a medicament, preferably a tablet.
A method for coating a medicament, comprising the steps of a) mixing a solution comprising a polyol, a polymer, a solvent and optionally a plasticizer; b) spraying the solution of step a) on a medicament; c) allowing the evaporation of the solvent, wherein the polyol is mannitol or xylitol and the polymer is an aqueous soluble polymer or a cellulose based polymer.
The method of claim 10, wherein the mannitol is added during the mixing step a) at a w/w% concentration between 10% and 30%, preferably between 20% and 30%.
The method of claim 10 or 11, wherein the polyol crystallizes on the medicament surface during step c).
The method of any of claims 10 to 12, wherein the solvent is a water-based solvent, an alcohol, a ketone, an ester or a chlorinated hydrocarbon or a mix thereof.
The method of claim 13, wherein a water-based solvent is used and a second solvent during step a) is added at a w/w% concentration of up to 30% of the water-based solvent in order to improve evaporation during step c).
Use of mannitol in a coating solution or of a coating solution comprising mannitol, preferably according to any of claims 1 to 8, for imparting a white color to a medicament, preferably a tablet.

Description

Field of the invention The invention relates to coating solutions with improved covering and whitening effects on the surface of a medicament. Technical background Regulatory concerns regarding the use of titanium dioxide as a whitening pigment in coating formulations are on the rise, which makes it important to provide alternatives for formulation development. Classical approaches for titanium dioxide replacement include the use of other pigments like zinc oxide, calcium phosphate, magnesium carbonate or calcium carbonate. Sugar-based formulations have also been developed in order to enhance appearance, taste, and stability of pharmaceutical and non-pharmaceutical products in solid dosage forms. However, sugar-based solutions present their own disadvantages and limitations, for example due to considerable dosage form size increase, higher caloric content, or the effects on blood sugar levels. Recently, the replacement of sugar by sugar-free alternatives has been described in scientific literature. However, providing sugar-free alternatives with suitable whitening and covering effects remains a challenge. The whitening effect of a coating solution is not a mere aesthetic or marketing aspect. Among the many complex factors involved in the success or failure of a drug therapy are behavioral elements such as patient compliance. Compliance is notably impacted by feelings of fear, anxiety, and mistrust in a patient. Medicaments that are coated with an intense, sharp white color have been shown to convey several characteristics that significantly contribute to patient compliance, such as safety, purity, or calm. In practice, coating solutions are applied to medicaments by spraying. This process also presents challenges as it puts constraints on the potential compounds and their concentrations that might be selected for mixing in the coating solution. Objective problem to be solved To address these challenges, alternative sugar-free coating solutions are required which show a satisfactory whitening effect, are chemically stable and comply with drug requirements. Summary of the invention In one aspect, the invention relates to a coating solution comprising a polyol, a polymer, and a solvent, wherein the polyol is mannitol or xylitol and the polymer is an aqueous soluble polymer or a cellulose based polymer. In a second aspect, the invention relates to the use of the coating solution according to the invention as a coating of a medicament. In a third aspect, the invention relates to a method for coating a medicament, comprising the steps of a) mixing a solution comprising a polyol, a polymer, a plasticizer, and a solvent, b) spraying the solution of step a) on a medicament, and c) allowing the evaporation of the solvent, wherein the polyol is mannitol or xylitol and the polymer is an aqueous soluble polymer or a cellulose based polymer. In a fourth aspect, the invention relates to the use of mannitol in a coating solution for a medicament. In a fifth aspect, the invention relates to the use of mannitol in a coating solution or a coating solution comprising mannitol, preferably as described hereinafter, for imparting a white color to a medicament. Brief description of the figures Fig. 1 shows the results of the color measurement of different pigment containing films on the black color cards.Fig. 2 shows the results of the color measurements of mannitol containing films at different concentrations on the black color cards.Fig. 3 shows the results of the color measurements for mannitol coated tablets in comparison to calcium carbonate and titanium dioxide. Detailed description of the invention In one aspect, the invention relates to a coating solution comprising a polyol, a polymer, and a solvent, wherein the polyol is mannitol or xylitol and the polymer is an aqueous soluble polymer or a cellulose based polymer. The coating solution according to the invention provides a coating of a medicament. The coating solution according to the invention provides a strong whitening and covering effect on the surface of a medicament without requiring titanium dioxide or any other insoluble or poorly soluble pigments. The coating solution also provides a coating of a medicament with outstanding light reflection as well as the covering of undesired colors of the core of the dosage form. The strong covering effect on a medicament, in turn protects the core of the dosage form from environmental factors such as light and humidity, thus enhancing the stability and shelf-life of the active pharmaceutical ingredient. Similar effects can be achieved when using sorbitol as the polyol. According to the invention, the medicament is preferably a solid dosage form such as a pill, a granule, a tablet or capsules. Most preferably, the medicament is a tablet. In some embodiments, the coating solution further comprises a plasticizer. A plasticizer increases the pliability and flexibility of the coating film produced from the coating solution. The pl