Film coating compositions with improved opacity and color uniformity and substrates coated therewith

Abstract

The present invention is directed dry powder film coating compositions for use on oral dosage forms such as compressed tablets and other orally-ingestible substrates. The film coating compositions include 30-50% by weight water-soluble polymer, 25-50% by weight of calcium carbonate, and 3-25% by weight of an opacifying enhancer. Oral substrates such as tablets coated with the film coating compositions are also disclosed and have high opacity, improved color uniformity and overall excellent appearance.

Description

FILM COATING COMPOSITIONS WITH IMPROVED OPACITY AND COLORUNIFORMITY AND SUBSTRATES COATED THEREWITHField of the Invention

[0001] The present invention relates to dry film coating compositions which, when coated onto orally ingestible substrates as an aqueous suspension, demonstrate improved opacity and color uniformity. The invention also relates to pharmaceutical and nutritional substrates or tablets having such film coatings, as well as methods of preparing the film coating compositions and coated substrates or tablets.Background of the Invention

[0002] Film coatings have been used on orally-ingestible substrates such as pharmaceutical and dietary supplement products for many years. Prior art coating formulations typically contain a polymer, a plasticizer, optional pigments, and other additives to improve aesthetics, functional properties or processability. With respect to pigments, both synthetic and natural colorants have been used in film coating formulations. Titanium dioxide has been commonly used as a white pigment and also to provide opacity to a coating formulation so that the underlying color of an orally- ingestible core does not interfere with the intended color of the coating formulation.Presently, there is increasing regulatory scrutiny of titanium dioxide, which has led to an emerging formulation trend to avoid the use of titanium dioxide by some manufacturers of orally-ingestible substrates. Calcium carbonate and starch have been used in some cases as replacements for titanium dioxide. However, the opacity of substitutes for titanium dioxide is much lower than that of titanium dioxide.

[0003] TiCh-free polyvinyl alcohol (PVA)-based systems when using calcium carbonate have significant opacity and color uniformity issues compared to hydroxypropyl methylcellulose (HPMC)-based systems. As a result, most available TiCh-free systems with sufficient opacity for use with pharmaceuticals are HPMC -based. There is a need therefore to provide a PVA-based TiCh-free coating with high opacity and improved color uniformity. The present invention addresses this need.Summary of the Invention

[0004] In a first aspect of the invention there are provided film coating compositions which demonstrate improved opacity and color uniformity when coated onto orally ingestible substrates. The compositions are preferably in powder form and are applied to tablets and the like as an aqueous suspension. The invention also relates to pharmaceutical and nutritional substrates or tablets having such film coatings, as well as methods of preparing the film coating compositions and coated substrates or tablets. The film coating compositions can be titanium dioxide free.

[0005] The dry film coating compositions can include: 30-50% by weight water-soluble polymer; 25-50% by weight of calcium carbonate; and 4.5-25% by weight of an opacifying enhancer. A preferred water-soluble polymer is polyvinyl alcohol (PVA) and one preferred opacifying enhancer is an amorphous form of magnesium aluminometasilicate available under the tradename Neusilin®, having the compendial name (JP, USP / NF & EP) magnesium aluminometasilicate.

[0006] The film coating compositions of the invention, i.e. those comprising: a. about 30-50% by weight water-soluble polymer; b. about 25-50% by weight of calcium carbonate; and c. about 3-25% by weight of an opacifying enhancer, have distinguishable properties in that when they are applied as an aqueous dispersion having a pH of less than or equal to 8.0 to a substrate to a weight gain of from about 2 to about 6% by weight, the film coating has % opacity of > 80.

[0007] The invention also includes aqueous dispersions containing the above-mentioned film coating compositions. The dispersions have a pH of less than or equal to 8.0, and contain from about 5-30% by wt of the film coating compositions, the % by weight being based upon solids content. These film coating dispersions can be applied to substrates such as oral tablets or the like to a weight gain of from about 0.5 to about 6% and the resultant film coatings have % opacity of > 80.

[0008] As a result of the invention, an improved film coating is provided which allows the artisan to film coat tablets and the like while maintaining high levels of opacity and color uniformity without the use of titanium dioxide.Brief Description of the Drawings

[0009] Figure 1 is a graph showing comparative L-Values for tablets having the coatings made in Example 3.Detailed Description of the Invention

[0010] For purposes of the present invention, the following terms are given further clarification as to their meanings:

[0011] “orally-ingestible substrate” shall be understood to mean any pharmaceutically acceptable dosage form, e.g. tablet, capsule, caplet, etc. or any other veterinary, nutritional, or confectionary product intended to be swallowed;

[0012] “dry powder” shall be understood to mean powders which are relatively dry to the touch rather than powders which are essentially without liquid content;

[0013] “ambient temperature” shall be understood to mean temperatures generally in the range of from about 20°C (68°F) to about 30°C (86°F) + / -3°C;

[0014] “about” shall be understood to mean approximately, roughly, around, or in the regions of; when the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term “about” can modify a numerical value above and below the stated value by a variance of, e g., 5-10 percent, up or down (higher or lower);

[0015] “fully formulated” as it relates to film coating systems shall be understood to include dry powder mixtures or aqueous dispersions containing all of the components necessary for film coating an orally ingestible substrate such as a compressed tablet in a manner consistent with good manufacturing practice (GMP) in the pharmaceutical and nutritional supplement industries.

[0016] In one aspect of the invention there are provided dry film coating compositions comprising: about 30-50% by weight water-soluble polymer; about 25-50% by weight of calcium carbonate; and about 4.5-25% by weight of an opacifying enhancer.

[0017] The water soluble polymer in most aspects of the invention is polyvinyl alcohol (PVA). Alternatively, a non-limiting list of suitable water soluble polymers includes not only PVA but also polyvinyl alcohol-polyethylene glycol graft copolymers (e.g. Kollicoat IR), hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone PVP, and vinyl pyrrolidone / vinyl acetate copolymers PVP-VA. Mixtures of the foregoing either with or without PVA are also contemplated for use herein.

[0018] Preferred grades of HPMC are lower viscosity grades such as those with aqueous solution viscosities of 1, 3, 5, 6, 15 and 50 centipoise (cP) when dissolved at 2% weight / volume in water.

[0019] Preferably, all of the water-soluble polymers are of sufficiently small particle size, preferably less than 250 microns, to facilitate dissolution into ambient water when forming the aqueous coating solutions. These polymers may be used alone or together.

[0020] In some aspects of the invention, the amount of water-soluble polymer is from about 30 to about 40% by weight of the powder composition. Similarly, the amount of calcium carbonate present in the dry composition can be from about 30 to about 40% by weight.

[0021] An opacifying agent such as calcium carbonate enhances the hiding power of a film coating such that the color of the underlying substrate is not visualized, allowing the intended color of the coating alone to be observed. The amount of calcium carbonate included in the powder mixtures of the present invention as described above is an amount which is sufficient to provide a measurable increase in the opacity of the film coating after application to the orally-ingestible substrate.

[0022] In many preferred aspects of the invention, the properties of the opacifying agent can be enhanced using an opacifying enhancer such as the aforementioned preferred Neusilin, a synthetic, amorphous form of magnesium aluminometasilicate available from Fuji Chemical Industries. In other aspects of the invention, the opacifying enhancer can comprise Syloid, a mesoporous silicon dioxide available from Grace or colloidal silicon dioxide. Another suitable opacifying enhancer is magnesium aluminosilicate. Still further aspects of the invention include mixtures of the foregoing, with the combination still being within the weight ranges provided herein, i.e. about 4.5-25% by weight or about 5-15% by weight for the opacifying enhancer.

[0023] The dry powder compositions of the invention can also include viscosity enhancers, microcrystalline cellulose, plasticizers, and mixtures thereof as well as ancillary excipients commonly found in fdm coating compositions if desired. One preferred viscosity enhancer is xanthan gum. Alternatively, the viscosity enhancer can beselected from among one or more pharmaceutically acceptable gums including the aforementioned xanthan gum, as well as sodium alginate, guar gum, locust bean gum, HPMC and mixtures thereof. When included, the viscosity enhancer can be present in an amount of 0.25-1% by weight. The film coating compositions can also include up to 2% by weight of a wax such as carnauba wax or another pharmaceutically acceptable wax.

[0024] The film coating compositions can also include microcrystalline cellulose (MCC,) present in an amount of up to 15% by weight.

[0025] The compositions of the invention can also include a plasticizer, present in an amount of up to 15% by weight, with amounts of from about 5 to about 10% by weight being preferred. In many aspects, the preferred plasticizer comprises polyethylene glycol (PEG). Preferred PEG’S are solid such as those for example having a molecular weight of from about 3,000 to about 8,000. Other plasticizers known to those of ordinary skill in the art can be used if desired as well.

[0026] As mentioned, it is an object to provide a fdm coating composition, preferably a PVA-based fdm coating system which is free of titanium dioxide. However, titanium dioxide can be included in addition to the ingredients described herein. Other ancillary ingredients common to fdm coating arts such as a glidant, a pigment, etc. can be included if desired.

[0027] Some preferred dry, powder fdm coating compositions of the invention are those in which the water-soluble polymer is polyvinyl alcohol, present in an amount of about 30-40% by weight; the calcium carbonate is present in an amount of about 30-40% by weight; and the opacifying enhancer is magnesium aluminometasilicate, i.e. Neusilin, present in an amount of 5-25% by weight. Such preferred compositions also can include a plasticizer such as polyethylene glycol 8000, present in an amount of 5-10% by weight, a viscosity enhancer such as xanthan gum, present in an amount of 0.25-1% and about 1% by weight carnauba wax, the total of the ingredients, of course, amounting to 100%.

[0028] The powder mixtures are prepared using standard dry blending or mixing techniques known to those of ordinary skill. For example, the ingredients are individually weighed, added to a suitable apparatus, and blended for a sufficient time until a substantially uniform mixture of the ingredients is obtained. The time required toachieve such substantial uniformity will, of course, depend upon the batch size and apparatus used.

[0029] As mentioned above, batch sizes will vary upon need. A non-limiting list of suitable blending devices include diffusion blenders such as a cross flow, V-blender, or hub blender, available from Patterson-Kelly, or convection blenders, such as Ruberg or VM blenders, available from Azo and Readco, respectively, may be used. Blending of the aforementioned formulations may also be achieved by processing ingredients into a granular form to produce a non-dusting granular coating composition by methods including, but not limited to, wet massing, fluid bed granulation, spray granulation and dry compaction, roller compaction or slugging. Other manners of blending will be apparent to those of ordinary skill.

[0030] Some preferred fdm coating powder compositions in accordance with the invention include:

[0031] It will be understood from the foregoing that the preferred dry film coating compositions will include at least 30-50% of the film forming polymer such as PVA, 25- 50% calcium carbonate and 4.5-25% of the opacifying enhancer. The remainder of the compositions are those optional ingredients described herein with the understanding that the total amount of all ingredients in the dry blend will be 100% by weight.

[0032] Further aspects of the invention include aqueous dispersions prepared by mixing the powder film coating compositions described herein with water. For purposes ofillustration and not limitation, an aqueous dispersion having about 20% non-water ingredients can be formed by dispersing 100 parts of a blended powder mixture described hereinabove into 400 parts of ambient temperature water. The water is weighed into a suitable vessel, i.e. one with a diameter approximately equal to the depth of the final suspension. A low shear mixer, preferably one having a mixing blade with a diameter about one third the diameter of the mixing vessel, is lowered into the water and turned on to create a vortex from the edge of the vessel down to about just above the mixing blade to prevent entrapment of air. Generally, the aqueous dispersions will contain from about 5-30% solids, i.e. of the film coating ingredients. Preferably, the aqueous dispersions of the invention will have a pH less than or equal to 8.0, or in the range of from about 6.0 to about 8.0.

[0033] The 100 parts of dry film coating composition is added to the vortex at a rate where there is no excessive buildup of dry powder. The speed and depth of the mixing blade is adjusted to avoid air being drawn into the suspension so as to avoid foaming. The suspension is stirred at low speed, preferably 350 rpm or less, for a time sufficient to ensure that a homogenous mixture is formed. Using the above batch size as a guide, about 45 minutes mixing time is required. The suspension is then ready for spraying onto pharmaceutical substrates and the like. Those of ordinary skill will also realize that there are many ways of preparing a substantially homogenous mixture of the solids in water and that the scope of the invention is in no way dependent on the apparatus used. It is contemplated that suitable aqueous dispersions will contain from about 5 to about 30% and preferably from about 15 to about 25% or about 20% non-water ingredients, i.e. solids, therein.

[0034] The pH of the aqueous dispersions of the present invention being less than or equal to 8.0 can be advantageous. For example, an aqueous dispersion hydrated at 20% solids will have a pH in the range of from about 6.0 to about 8.0. Many active pharmaceutical ingredients included in oral solid dosage forms are acidic or salts with acidic compounds like HC1, which could potentially interact with more alkaline film coating systems and could potentially affect the solubility of the active. Film coatings such as those described herein with a more neutral pH are desirable to reduce the potential for this interaction.

[0035] Another important aspect of the invention is that the film coating offers a % opacity > 80 when coated to a coating density of 5.00 mg / cm2(equivalent to 4% weight gain, hereinafter “WG” on a 330 mg tablet). Coatings with a lower opacity < 80 have poor color uniformity and inconsistent visual appearance. While this can sometimes be overcome by applying higher weight gains of a lower opacity coating, this approach is not desirable from an economical or a process capacity stand point.

[0036] To measure the opacity, the coating would first have to be applied to a mixture of uncoated white tablets and tablets previously sub-coated with a black HPMC -based coating. Then the lightness value (L*) of top coated tablets with black subcoat and the top coated tablets without the black subcoat were measured using a Datacolor reflectance spectrophotometer. The lightness value (L*) of coated tablets was determined on a scale of 0-100, where 0 and 100 correspond to the darkest and lightest shades measurable. A white tile supplied by Datacolor was used as the standard. The Opacity is the ratio of revalues of the black tablets over the white tablets multiplied by 100.

[0037] Another important aspect of the invention includes orally-ingestible substrates which have been film coated with the aqueous dispersions described herein. The film coated orally-ingestible substrates will, in most aspects of the invention, include the film coating applied to the orally-ingestible substrate to a weight gain of from about 0.5 to about 6%. Some film coatings substrates have % opacity of > 80 when the orally- ingestible substrates are film coated to a weight gain of from about 3- 6% by weight of the orally-ingestible substrate. In alternative aspects of the invention, similar % opacity can be obtained with film coatings to weight gains of less than 3% and greater than 6%.

[0038] The coated ingestible substrates have a visually attractive appearance, are free or substantially free from cracks, pick marks and other surface defects. This combination of properties for a coating system is clearly advantageous over the prior art and existing marketed products, especially in the case of PVA-based film coating systems.

[0039] In accordance with some preferred embodiments, film coated substrates include a core portion having at least about 0.25 % wt of a titanium dioxide free or substantially titanium-free film coating prepared from a dispersion containing the previously dry film coating compositions described herein thereon. The film coating on the tablet or substrate has a % opacity of > 80 and the film coating includes a water soluble polymersuch as PVA, calcium carbonate and an opacifying enhancer selected from magnesium aluminometasillicate and mesoporous silicon dioxide and mixtures thereof.

[0040] The inventive film coatings can be formulated to be titanium dioxide-free, substantially free of titanium dioxide, i.e. having less than about 0.5% by wt., or with substantially reduced amounts of titanium dioxide commonly found in dry film coating compositions, e.g. 20-30% w / w less, thus providing the artisan with a useful alternative to currently-available film coatings having high degrees of opacity and which are largely dependent upon titanium dioxide for achieving that result.

[0041] The invention also includes methods of increasing the opacity of a film coating on an orally-ingestible substrate. These methods comprise preparing an aqueous dispersion as described herein and applying the aqueous dispersion to an orally-ingestible substrate as a film coating until a weight gain of at least about 0.5% is achieved. In some aspects, the weight gain of the film coating on the orally-ingestible substrate is about 4% by weight.

[0042] As will be described in the examples below, the methods include applying the film coating compositions as aqueous suspensions to the surfaces of orally ingestible substrates. The film coating can be applied as part of a pan coating or spray coating process commonly used to coat such articles. The amount of coating applied will depend upon several factors, including the nature and functionality of the film coating, the substrate to be coated and the apparatus employed to apply the coating, etc. In some embodiments, the substrates will be tablets and will be coated to a theoretical weight gain of from about 0.25 or 0.5 to about 5.0%. For economic reasons, it is preferred to apply as low a weight gain as possible while obtaining acceptable opacity and overall aesthetic characteristics. As mentioned above, the coating solutions of the present invention may also include auxiliary ingredients in addition to the powder mixture and the water.

[0043] The coated, orally-ingestible substrates described above can also include a subcoat film coating between the orally-ingestible substrate and the inventive film coating. The subcoat selected is preferably based on an edible film coating composition that is compatible with and adheres to both the orally ingestible substrate and the inventive coating. Thus, the artisan may choose from a wide variety of pharmaceutical or food-acceptable coatings for use as subcoats in the present invention. The subcoat is alsoapplied to the substrate to provide from about a 0.25 to about a 5.0% weight gain to the orally-ingestible substrate.

[0044] Regardless of the method employed or the specific materials included in the film coating compositions, the orally-ingestible substrates of the present invention will include a film coating applied to a weight gain sufficient to obtain acceptable opacity and overall aesthetic characteristics.EXAMPLES

[0045] The following examples serve to provide further appreciation of the invention but are not meant in any way to restrict the effective scope of the invention. All ingredients are expressed as being by weight%.EXAMPLE 1

[0046] A preferred formulation for an inventive dry coating composition is the following:100.0Preparation of the Dry Film Coating Composition:

[0047] The dry film coating composition was prepared by adding the ingredients into a laboratory blender and blending for 5 minutes until a homogenous mixture was produced.Preparation of the Aqueous Dispersion:

[0048] The dry film coating composition (100 parts) was dispersed into 400 parts of ambient temperature water to make an aqueous coating suspension having 20% w / w nonwater ingredients. The water was weighed into a vessel with a diameter approximatelyequal to the depth of the final dispersion. A low shear mixer was lowered into the water and turned on to create a vortex from the edge of the vessel down to just above the mixing blade to prevent entrapment of air. The 100 parts of dry film coating composition was added to the vortex at a rate where there was no excessive buildup of dry powder or foam. The speed and depth of the mixing blade was adjusted to avoid air being drawn into the suspension so as to avoid foaming. The suspension was stirred at low speed (350 rpm or less) for 45 minutes to form a homogeneous aqueous dispersion suitable for coating. The pH of this dispersion was evaluated.Coating of Tablets:

[0049] Placebo tablets (3.0 kg), which was a mixture of uncoated white placebo tablets and tablets previously sub-coated with a black HPMC -based coating, were coated with the aqueous dispersion of Example 1 at a spray rate of 20 grams / min in a Labcoat I (O’Hara Technologies Inc., Canada) outfitted with a 15” fully perforated pan. A theoretical coating weight gain of 4.0% was applied to the tablets. The resulting coated tablets were smooth, non-tacky, and free from cracks or other surface defects. The coating strongly adhered to the tablet surface, and the coated tablets had no visible friability. The black placebo tablets were purposefully selected to challenge the opacification properties of the inventive coating. As the weight gain of the inventive coating was applied, the color of the tablets gradually became white. The whiteness of the tablets coated to 4% weight gain were instrumentally analyzed to determine whiteness / lightness as described below.

[0050] Determination of Opacity: The lightness value (L*) of top coated tablets with black subcoat and the top coated tablets without the black subcoat were measured using a Datacolor reflectance spectrophotometer. The lightness value (L*) of coated tablets was determined on a scale of 0-100, where 0 and 100 correspond to the darkest and lightest shades measurable. A white tile supplied by Datacolor was used as the standard. The Opacity is the ratio of L-values of the black tablets over the white tablets multiplied by 100. Opacity: 87%; pH @ 20% solids: 7.8.Comparative Examples A-B

[0051] Comparative formulations are prepared according to the following ratios and are evaluated using the same methods as Example 1.

[0052] The resultant coated tablets have less than the desired levels of opacity and higher than desirable pH. The opacity for A and B were 67% 59%, respectively. The pH for A and B are pH 8.1 and 8.3.EXAMPLE 2

[0053] In this example, each coating formulation was top-coated at 20% solids onto 3 kg of black sub-coated placebos in a 15” fully perforated side-vented coating pan from O’Hara Technologies (Labcoat II). Tablets were collected at 3, 4, and 5% weight gains.The coated tablets were measured using a Datacolor spectrophotometer and the L-valueswere recorded (n=10). The L-value indicates the lightness of the sample from 0 to 100, with higher numbers representing whiter and more opaque samples. The following formulations were tested:

[0054] PVA-based formulation containing TiO2Control #1

[0055] PVA-based formulation containing calcium carbonate Without Opacity EnhancerControl #2

[0056] A formulation made in accordance with Example 1Opacity:

[0057] The inventive PVA-based TiO2-free formulation containing the Neusilin and the PVA-based formulation containing TiO2 look white suggesting that both systems have sufficient opacity and whiteness to hide the color of the black sub-coat, with the TiO2- free formulation being only slightly darker. In contrast, the non-optimized PVA-based formulation containing calcium carbonate has a significant dark gray tint suggesting poor opacity. See Table below:

[0058] L-Values for Black Sub-coated Placebos with Top-Coats at Different Weight Gains[ PVA-based w / Calcium Carbonate, no opacity enhancer s 61.33 [ 67.00 ; 70 34

[0059] The L-Value results using the Datacolor show that the PVA-based formulation with TiCh has significantly better opacity compared to the PVA-based formulation containing calcium carbonate but no opacity enhancer, with a 26-unit difference at 4% WG. The inventive PVA-based TiCh-free formulation containing the opacity enhancer is much closer in opacity to the PVA-based formulation with TiCh, with an 8-unit difference in L-value at 4% WG. The inventive formulation has significantly better opacity compared to the PVA-based formulation containing only calcium carbonate, with a 20-unit difference at 4% WG.EXAMPLE 3

[0060] In this example, each formulation was coated at 20% solids onto 17kg of 500mg acetaminophen caplets in a 24” fully perforated side-vented coating pan from O’HaraTechnologies (Labcoat II). Tablets were collected at 3, 4, and 5% weight gains. Caplets were measured using the Datacolor spectrophotometer (n=20). Delta E (DE) values for each individual caplet was compared to a reference standard (5%wg average). DE values greater than 2.5 suggest that non-uniformity of color would be visually apparent. The following formulations were tested:

[0061] PVA-based formulation containing TiCh with FD&C Blue #2 Aluminum Lake (Blue #2) Control #2

[0062] PVA-based formulation Without Opacity Enhancer containing calcium carbonate with Blue #2

[0063] A formulation made in accordance with Example 1 with Blue #2Color Uniformity:

[0064] Figure 1 shows the color uniformity of the different formulations containing Blue #2 at 3, 4, and 5% WG on acetaminophen caplets. The PVA-based formulation with TiCh has the best color uniformity, reaching the acceptable limit (DE<2.5) at 3% WG with little variation within samples. The PVA-based formulation with calcium carbonate but no opacity enhancer requires more than 5% WG to reach sufficient color uniformity and has much larger variation within samples. The inventive PVA-based TiCh free formulation has good color uniformity, reaching the acceptable limit at 4% WG and lower variation at all weight gains compared to the PVA-based formulation with calcium carbonate but without the opacity enhancer. (Figure 1).Example 4

[0065] In this example formulations 4A, 4B and 4C were prepared according to the following ratios and are evaluated using the same methods as Example 1. The opacity of formulations 4A, 4B and 4C were 84%, 90% and 83%, respectively. The dispersion pH at 20% solids were 7.8, 7.8 and 8.0, respectively. Example 4 shows high opacity and low dispersion pH can be achieved with other water soluble polymers.Example 5

[0066] In this example formulations 5A, 5B and 5C were prepared according to the following ratios and are evaluated using the same methods as Example 1. The opacity of formulations 5A, 5B and 5C were 81%, 84% and 85%, respectively. The dispersion pH at 20% solids were 7.9, 8.0 and 8.0, respectively. Example 5 shows high opacity and low dispersion pH can be achieved with colloidal silica or mesoporous silica.Example 6 Comparative Examples C-I

[0067] Comparative formulations are prepared according to the following ratios and are evaluated using the same methods as Example 1.

[0068] Although the resultant coated tablets meet the desired levels of opacity, the coating dispersion pH was higher than pH 8.0, when prepared at 20% solids. The opacity of formulations C-I were 87%, 85%, 85%, 85, 81, 84 and 87 respectively. The dispersion pH at 20% solids were 8.2, 8.1, 8.1, 8.3, 8.3, 8.2 and 9.6 respectively and therefore outside the acceptable range.EXAMPLE 7

[0069] In this example, each coating formulation contains red beet pigment. This colorant is known to bleach in high pH environments. Each formulation was coated at 20% solids onto 1 kg of placebos in a 12” fully perforated side-vented coating pan fromO’Hara Technologies (Labcoat I). Tablets were collected at 4% weight gains. Tablets were inspected visually for any differences.

[0070] A formulation made in accordance with Example 1 containing red beet pigment.

[0071] PVA-based formulation containing calcium silicate, red beet pigment, and no opacity enhancer.

[0072] All formulations are the desired light pink color when in powder form. After being dispersed in water at 20% solids, the inventive PVA-based TiCh free formulation continue to have the desired light pink color. After coatings were performed, the resultant tablets of this formulations continue to have the desired light pink color. The PVA-based formulation with calcium silicate and no opacity enhancer starts with a pink color as a powder. However, when the powder is dispersed into water, the dispersion initially started off as pink, but then quickly turned yellow within a few minutes of mixing, due to the high pH of the calcium silicate. Resultant tablets of this formulation are yellow which is not the desired color.EXAMPLE 7

[0073] The example formulation is prepared according to the following ratios and are evaluated using the same methods as Example 1.

[0074] The resultant coated tablets meet the desired levels of opacity (90%) and pH (7.72).CONCLUSION

[0075] This study shows that the PVA-based TiO2-free formulations of the invention achieved good opacity and color uniformity at 4% WG. This is a significant improvement compared to other PVA-based TiO2-free systems without enhancers.

Claims

WHAT IS CLAIMED IS:

1. A film coating composition, comprising: i) about 30-50% by weight water-soluble polymer; ii) about 25-50% by weight of calcium carbonate; and iii) about 4.5-25% by weight of an opacifying enhancer, wherein the film coating composition is in the form of a powder mixture.

2. The film coating composition of claim 1, wherein when said film coating composition is applied as an aqueous dispersion having a pH of less than or equal to 8.0 to a substrate to a weight gain of from about 2 to about 6% by weight, the film coating has % opacity of > 80.

3. The composition of claim 1, wherein the water soluble polymer is polyvinyl alcohol.

4. The composition of claim 1, wherein the water soluble polymer is selected from the group consisting of polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone PVP, vinyl pyrrolidone / vinyl acetate copolymers PVP-VA and mixtures thereof.

5. The composition of claim 1, wherein the amount of water-soluble polymer is about 30-40% by weight.

6. The composition of claim 1, wherein the amount of calcium carbonate is about 30- 40% by weight.

7. The composition of claim 1, wherein the amount of opacifying enhancer is about 4.5 to about 15 % by weight.

8. The composition of claim 1, wherein the opacifying enhancer is magnesium aluminometasilicate (Neusilin®).

9. The composition of claim 1, wherein the opacifying enhancer comprises Syloid, mesoporous silicon dioxide or colloidal silicon dioxide.

10. The composition of claim 1, further comprising a member of the group consisting of viscosity enhancers, microcrystalline cellulose, plasticizers, and mixtures thereof.

11. The composition of claim 10, wherein the viscosity enhancer is xanthan gum.

12. The composition of claim 10, wherein the viscosity enhancer is present in an amount of about 0.25-1% by weight.

13. The composition of claim 1, further comprising up to about 2% by weight of a wax.

14. The composition of claim 10, wherein the microcrystalline cellulose is present in an amount of up to about 20% by weight.

15. The composition of claim 10, wherein the plasticizer is present in an amount of up to about 15% by weight.

16. The composition of claim 10, wherein the plasticizer comprises polyethylene glycol.

17. The composition of claim 1, wherein the composition is free of titanium dioxide.

18. A dry fdm coating composition of claim 1, wherein i) the water-soluble polymer is polyvinyl alcohol and is present in an amount of about 30-40% by weight; ii) the calcium carbonate is present in an amount of about 30-40% by weight; and iii) the opacifying enhancer is magnesium aluminometasilicate, present in an amount of 5-15% by weight,said dry film coating composition further comprising a plasticizer, said plasticizer being polyethylene glycol 8000 and being present in an amount of about 5-10% by weight, a viscosity enhancer, said viscosity enhancer being xanthan gum and being present in an amount of about 0.25-1% and about 1% by weight carnauba wax.

19. An aqueous dispersion prepared by mixing a composition of claim 1 in water.

20. The aqueous dispersion of claim 19, wherein dispersion contains from about 5-30% solids.

21. The aqueous dispersion of claim 19, wherein the dispersion contains 20% solids and has a pH in the range of from about 6.0 to about 8.0.

22. An orally-ingestible substrate film coated with the aqueous dispersion of claim 19.

23. The film coated orally-ingestible substrate of claim 22, wherein the film coating is applied to a weight gain of from about 0.25 to about 6%.

24. The film coated orally-ingestible substrate of claim 22, wherein the film coating has % opacity of > 80 when the orally-ingestible substrate is film coated to a weight gain of from about 2- 6% by weight of the orally-ingestible substrate.

25. A film coated substrate comprising a core portion having at least about 0.25 % wt of a titanium dioxide free film coating thereon, said film coating film coating having a % opacity of > 80 and said film coating comprising a water soluble polymer, calcium carbonate and an opacifying enhancer selected from the group consisting of magnesium aluminometasillicate, mesoporous silicon dioxide and mixtures thereof.

26. A method of increasing the opacity of a film coating on an orally-ingestible substrate, comprising film coating an orally-ingestible substrate with an aqueous dispersion of claim 19 until a weight gain of at least about 0.25% is achieved.

27. The method of claim 26, wherein the weight gain of the film coating on the orally- ingestible substrate is about 4% by weight.