COATING COMPOSITION FREE OF TITANIUM DIOXIDE

Abstract

Disclosed is a coating composition including, in relation to 100% of the weight thereof: 10-90 wt. % of at least one film-forming polymer selected from methyl cellulose, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, hydroxy ethyl cellulose, sodium carboxy methyl cellulose, ethyl cellulose, PVA (polyvinyl alcohols), PVA-PEG (polyethylene glycol) copolymers, polyvinyl acetate, polyvinyl pyrrolidones (PVP), vinylpyrrolidone-vinyl acetate copolymers, alginates, pectin, arabic gum, guar gum, carrageenans, xanthan gum, inulin, chitosan, methacrylic acid copolymer, ethyl acetate, or polyethylene glycol-polypropylene glycol (PEG-PPG) copolymer; 0-50 wt. % of at least one auxiliary coating agent selected from diluents, surfactants, plasticisers and anti-foaming agents; and 10-50 wt. % of a whitening filler free of titanium dioxide including at least one alkaline or alkaline earth salt of a fatty acid and at least one cellulose compound selected from cellulose, cellulose powder, microcrystalline cellulose, or a mixture of the components.

Claims

1. A coating composition comprising, per 100% of its weight: from 10% to 90% by weight of at least one film-forming polymer chosen from methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethylcellulose sodium, ethyl cellulose, PVA (polyvinyl alcohols), PVA/PEG (polyethylene glycol) copolymers, polyvinyl acetate, polyvinylpyrrolidones (PVP), vinylpyrrolidone/vinyl acetate copolymers, alginates, pectin, gum arabic, guar gum, carrageenans, xanthan gum, inulin, chitosan, methacrylic acid/ethyl acetate copolymer or polyethylene glycol/polypropylene glycol (PEG/PPG) copolymer, from 0% to 50% by weight of at least one auxiliary coating agent chosen from diluents, surfactants, plasticizers or antifoaming agents, and from 10% to 50% by weight of a whitening filler devoid of titanium dioxide comprising at least one alkali metal or alkaline earth metal fatty acid salt and at least one cellulose compound chosen from cellulose, cellulose powder, microcrystalline cellulose or a mixture of these components.

2. The coating composition as claimed in claim 1, wherein said at least one auxiliary coating agent is chosen from diluents; surfactants; plasticizers; or antifoaming agents.

3. The coating composition as defined in claim 1, wherein said at least one film-forming polymer is hydroxypropyl methylcellulose.

4. The coating composition as defined in claim 1, wherein the whitening filler is composed, per 100% of weight, of 20% to 80% by weight of alkali metal or alkaline earth metal fatty acid salt and of 20% to 80% by weight of a cellulose compound.

5. The coating composition as defined in claim 1, wherein the alkali metal or alkaline earth metal fatty acid salt is chosen from the monovalent salts of fatty acids and alkali metal cations and/or the divalent salts of fatty acids and alkaline earth metal or other metal cations.

6. The coating composition as claimed in claim 5, wherein the alkali metal or alkaline earth metal fatty acid salt is magnesium stearate.

7. The composition as claimed in claim 6, wherein at least 90% by volume of the particles of said at least one cellulose compound have a diameter of less than or equal to 60 micrometers.

8. The coating composition as defined in claim 1, in the form of an aqueous dispersion, of a powder or of ready-for-use granules.

9. A process for the preparation of the coating composition as defined in claim 1 and which is provided in the form of a dry powder, comprising the following stages: a stage (a) of mixing the film-forming polymer, the whitening filler according to the invention and, if necessary or if desired, one or more other coating auxiliaries, a stage (b) of grinding the mixture resulting from stage (a), in order to form said coating composition.

10. A process for the preparation of a coating composition as defined in claim 1 and which is provided in the form of ready-for-use granules, comprising the following stages: a stage (a1) of wetting the mixture of film-forming polymer, of the whitening filler according to the invention and, if necessary or if desired, of one or more other coating auxiliaries with a binding solution, in order to obtain a wet mass containing from 30% to 60% of water, a stage (b1) of drying the wet mass obtained in stage (a1) and, if desired or if necessary, a stage (c1) of grading the dried mass obtained in stage (b1), in order to obtain said coating composition.

11. A process for the preparation of the coating composition as defined in claim 1 and which is provided in the form of an aqueous dispersion, comprising the following stages: a stage (a2) of dispersing the film-forming polymer, the whitening filler according to the invention and, if necessary or if desired, one or more other coating auxiliaries in an aqueous phase, a stage (b2) of grinding the mixture resulting from stage (a1), in order to form said coating composition.

12. An ingestible solid form having a coating comprising the coating composition as defined in claim 1.

13. The coating composition of claim 1 comprising a whitening filler devoid of titanium dioxide comprising at least one alkali metal or alkaline earth metal fatty acid salt chosen from the monovalent salts of fatty acids and alkali metal cations and/or the divalent salts of fatty acids and alkaline earth metal or other metal cations, and at least one cellulose compound chosen from cellulose, cellulose powder, microcrystalline cellulose or a mixture of these components.

Description

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Examples

[0133] The qualifying of the film-coating compositions as described above as alternatives to compositions containing titanium dioxide, exhibiting in particular satisfactory characteristics of white and opacifying coloring, is established by the implementation of analyses as described below.

[0134] Tablets are film-coated with the film-coating compositions to be evaluated.

[0135] The film-coated tablets are studied according to the combination of the two following methods:

[0136] 1. Visual Method

[0137] The visual quality of the film coatings on the tablets is evaluated under standardized conditions of exposure to daylight or by means of a Konica Minolta Just Normlicht light cabin; at least two evaluators are required. The three parameters studied are: [0138] the smooth nature of the surface film of tablets; graded from 1 to 4 (1: Smooth-2: Bumps-3: Granular-4: Very granular); the best result being to obtain a smooth surface film; only a grade of 1 will be considered satisfactory, [0139] the coverage over the surface of the tablets; graded from 1 to 3; the best result being notified by a grade of 3; only the grades 2 and 3 will be considered satisfactory, [0140] as well as the coverage of the edges; graded from 1 to 4; the best result being notified by a grade of 4; only the grades of 3 and 4 will be considered satisfactory.

[0141] 2. Colorimetric Method, Chroma Meter

[0142] The L*a*b* color space, defined by the CIE in 1976 and also called CIELAB space, is currently one of the most widely used to measure the color of objects in different fields of activity. It covers the entire spectrum visible to the human eye and represents it in a uniform way. It thus makes it possible to describe all the visible colors.

[0143] In this, a color is pinpointed by three values: [0144] L*, lightness (0 for black to 100 for white), [0145] a* and b*, the chromaticity coordinates, ranging from green to red and from blue to yellow respectively with values ranging from 120 to +120.

[0146] Use is made here of the Konica Minolta CR-400 colorimeter/chroma meter in order to acquire the color on the tablets film-coated with coating solution(s).

[0147] Two criteria in particular are studied: [0148] lightness L*, since we are in shades of whitethis measurement will make it possible to measure the impact of the film coating on the final color of the tablets and thus to differentiate the impact of the different ingredients+=only L* values of greater than or equal to 90 will be considered satisfactory, [0149] also, the numerical calculation of the E, which makes possible a complete analysis of possible differences between a reference (for example a reference here with regard to titanium dioxide) and the tablet studied, by taking into account this time the L*, a* and b* parameters. The calculation formula is as follows: E=[(L1L2).sup.2+(a1a2).sup.2+(b1b2).sup.2]it is considered that a difference E5 is not visible to the human eye; in other words, a film-coated tablet exhibiting a value E>5 will be regarded as different from the reference taken into considerationthe formulation which has been used to film-coat it will thus be regarded as unsatisfactory.

[0150] It is the combining into a whole of the conclusions obtained with regard to these two methods which determines the ability of the new film-coating products to pertinently be an alternative to the film coatings containing titanium dioxide.

Example 1

[0151] Film-coating products are formulated in the powder form according to the following composition (not exhaustive):

TABLE-US-00001 Formulation F1 F2 F3 F4 F14 HPMC (hydroxypropyl 60% 60% 60% 60% 60% methylcellulose) Whitening filler*: Magnesium stearate 20% 20% 20% 20% 0% Calcium stearate 0% 0% 0% 0% 20% MCC (microcrystalline cellulose) 20% 0% 0% 0% 20% Cellulose powder 0% 20% 0% 0% 0% Calcium carbonate 0% 0% 20% 0% 0% Talc 0% 0% 0% 20% 0% *The various compounds tested exhibit a particle size profile, established by laser particle sizing, in accordance with the interval described above in the description of the invention. The % are by weight (for example, the Dv(90) of the microcrystalline cellulose used in the preparation of the formulations F1 to F4, as defined above, is less than or equal to 50 micrometers.

[0152] 500 mg placebo tablets with the following composition: 49.8% of microcrystalline cellulose, 49.6% of lactose and 0.6% of magnesium stearate, are film-coated with the various film-forming compositions. Some of these tablets are pre-film-coated with a Sepifilm PW Yellow I film-coating solution, inducing a yellow/orange coloring at the surface of the cores, in order to more precisely visualize the covering abilities, in particular of the various film-forming compositions to be tested.

[0153] The film coatings are carried out in a Profile Automation perforated turbine mixer charged with 1.2 kg of tablets; the dry deposit on the tablets is 5%.

[0154] Tablets film-coated with the commercial product Sepifilm PW White containing titanium dioxide are taken as reference.

[0155] The film-coated tablets are studied according to a combination of the following two methods:

[0156] 1. using the visual method described above,

[0157] 2. using the colorimeter/chroma meter as described above.

[0158] The following results are obtained:

[0159] 1. Evaluation according to the visual method:

TABLE-US-00002 Smooth character of the film (1: Smooth - Surface Coverage of 2: Bumps - 3: coverage the edges Granular - 4: ( to +; ( to +; Very granular) scale 1 to 3) scale 1 to 4) Film-coating 1 3 4 formulation F1 Film-coating 1 3 3 formulation F2 Film-coating 1 3 2 formulation F3 Film-coating 1 3 3 formulation F4 Film-coating 1 3 3 formulation F14

[0160] 2. Colorimetric evaluation with regard to the advantageous formulations:

TABLE-US-00003 Value of Value of L* on L* on tablets E* on tablets tablets film-coated not film-coated not film-coated beforehand with beforehand beforehand Sepifilm PW Yellow I Film-coating 97 4 90 formulation F1 Film-coating 97 4 90 formulation F2 Film-coating 96 4 88 formulation F4 Reference with 96 Reference 94 titanium dioxide* *This reference is a commercial product containing an identical proportion and identical nature of film-forming compound (HPMC), a proportion of whitening filler of the same order, with in particular the implementation of 20% of titanium dioxide.

[0161] Interpretation:

[0162] The superior performance of the formulations based on microcrystalline cellulose or cellulose powder is thus noticed. Talc is also advantageous on the scale of the first evaluation method but has fallen regarding the evaluation by colorimetry.

[0163] The colorimetry of these tests on cellulose compounds confirms the relevance of these compositions as a replacement for titanium dioxide.

Example 2

[0164] We wished to confirm the specificity of the (quantitative) synergy between the alkali metal or alkaline earth metal fatty acid compounds and the cellulose compounds (the two components of the whitening filler according to the invention). Various film-forming compositions containing, for whitening filler, the microcrystalline cellulose and magnesium stearate combination were prepared:

TABLE-US-00004 Formulation F5 F6 F7 F8 F9 F11 F12 F13 HPMC 60% 60% 60% 60% 60% 40% 0% 0% (hydroxypropyl methylcellu- lose) Starch 0% 0% 0% 0% 0% 0% 60% 0% (PC-10 starch) HPC 0% 0% 0% 0% 0% 0% 0% 60% (hydroxypropyl cellulose) Whitening filler: MCC 40% 30% 20% 10% 0% 30% 20% 20% (microcrystal- line cellulose) Magnesium 0% 10% 20% 30% 40% 30% 20% 20% stearate

[0165] Placebo tablets identical to those used in example 1 are employed. Some are film-coated beforehand with a Sepifilm PW Yellow I film-coating solution, inducing a yellow/orange coloring at the surface of the cores.

[0166] The film coatings are carried out in the Profile Automation perforated turbine mixer; the dry deposit on the tablets is 5%.

[0167] The film-coated tablets are studied using the visual method described above.

[0168] The following results are obtained:

[0169] 1. Evaluation according to the visual method:

TABLE-US-00005 Smooth character of the film (1: Smooth - Surface Coverage of 2: Bumps - 3: coverage the edges Granular - 4: ( to +; ( to +; Very granular) scale 1 to 3) scale 1 to 4) Film-coating 1 1 1 formulation F5 Film-coating 1 2 4 formulation F6 Film-coating 1 3 4 formulation F7 Film-coating 1 2 3 formulation F8 Film-coating 1 2 2 formulation F9 Film-coating 1 3 2 formulation F11 Film-coating 2 1 1 formulation F12 Film-coating 1 2 3 formulation F13

[0170] Interpretation:

[0171] The superior performance of the formulations F6, F7, F8 and F13, with respect to the formulations F5, F9, F11 and F12, is thus noticed.

Example 3

[0172] We wished to study the specificity of the particle size profile of the powders constituting the whitening filler.

[0173] Two film-forming compositions containing, for whitening filler, the microcrystalline cellulose and magnesium stearate combination were prepared:

TABLE-US-00006 Formulation FI FJ HPMC (hydroxypropyl 60% 60% methylcellulose) Whitening filler: MCC (microcrystalline cellulose) 20% 20% (fine particle (coarse particle size profile) size profile) Magnesium stearate 20% 20%

[0174] The particle size profile of the powders is measured by virtue of a Mastersizer 3000 laser particle sizer from Malvern, used in the dry route, at a pressure of 1 bar.

[0175] The particle size profiles of the microcrystalline celluloses studied are as follows:

MCC>d(v,50)=10-20 m,d(v,90)=40-60 m.Formulation I:

MCC>d(v,50)=100-120 m,d(v,90)=220-250 m.Formulation J:

[0176] Placebo tablets identical to those used in example 1 are employed. Some are film-coated beforehand with a Sepifilm PW Yellow I film-coating solution, inducing a yellow/orange coloring at the surface of the cores.

[0177] The film coatings are carried out in the Profile Automation perforated turbine mixer; the dry deposit on the tablets is 5%.

[0178] The visual method alone, described above, makes it possible to decide on the quality/relevance of the film-coating composition.

[0179] The following results are obtained:

TABLE-US-00007 Smooth character of the film (1: Smooth - Surface Coverage of 2: Bumps - 3: coverage the edges Granular - 4: ( to +; ( to +; Very granular) scale 1 to 3) scale 1 to 4) Film-coating 1 3 4 formulation I Film-coating 4 2 2 formulation J

[0180] Interpretation:

[0181] The importance of the choice of particle size profiles of the whitening filler on the performance of the film-coating composition is thus noticed, the formulation J being straight away considered unsatisfactory according to the visual evaluation method.