HK1098347A - Enteric coatings for orally ingestible substrates - Google Patents

Description

Enteric coating for orally ingestible substrates

Background

Technical Field

The field of the invention is enteric coatings for orally ingestible substrates (substrates), such as tablets and food supplements.

Description of the Prior Art

In this field, there have been a number of useful enteric-coated formulations including Acryl-EZE^®And Sureteric^®Both of which are prepared and sold by the assignee of the present application. However, all of the ingredients of currently marketed enteric coated formulations have been approved for food, nutritional supplement and pharmaceutical applications in every target market worldwide. Moreover, there continues to be a need in the food, nutritional supplement, and pharmaceutical markets to develop new, enteric-coated products that would allow the pharmaceutical or nutritional supplement companies to clearly stand out from competition.

A brochure entitled "Alginates for Pharmaceutical Applications" (code: PHARM/ALG/0800), published by International Specialty Products, which is incorporated herein by reference, indicates that Alginates such as sodium alginate have been used in certain commercially available tablet coating systems to achieve an enteric barrier in the stomach. It also indicates that alginate can be dissolved in water at a level of 5-10% and if a plasticizer such as glycerol or propylene glycol is added, a film with better integrity is produced. However, there is no disclosure or suggestion in the brochure of how to perform coating at solids level of above 10% in aqueous solution, which would result in a faster coating process and, overall, a more economical operation. Furthermore, increasing the concentration of the aqueous sodium alginate solution above 10% (w/w) will result in a thickening of the solution, which will make it difficult or impossible to express and spray the solution.

US 6,365,148 discloses a complex system (multiple systems) which achieves an enteric effect when coated on lactic acid bacteria particles. It is also disclosed that alginate alone or in combination with a "controlled release" top coat, which may consist of sodium alginate and/or ethyl cellulose, at low temperatures may be used to obtain an enteric effect. It has been demonstrated that either the controlled release layer alone (top coat) or the specific combination of ethylcellulose and sodium alginate in a single coating layer will not perform as an effective enteric coating. Moreover, the' 148 patent discloses the use of a limited amount of plasticizer, which is not necessary, nor most preferred for film-forming and special feel properties. For example, the' 148 patent does not describe the use of dibutyl sebacate and medium chain triglycerides (also referred to as fractionated coconut oil).

While the prior art has provided some improvements, there is a continuing need for improved enteric coating systems. The present invention meets this need.

Brief description of the invention

One subject of the present invention is the preparation of enteric coating systems which have a wide regulatory acceptance and can be applied to orally ingested substrates in a higher production process. In accordance with this and other subject matter, a preferred aspect of the present invention includes an enteric coating system comprising an aqueous dispersion of ethylcellulose and a substantially gastro-insoluble pore former (i.e.,insoluble at a pH of about 1 in the stomach). In a preferred aspect of the invention, the cellulose part of the film coating system is prepared by inclusion of Surelease^®To provide, Surelease^®A product of Colorcon, West Point, PA, which is a formulated product comprising an aqueous dispersion of ethylcellulose and a plasticizer. A preferred substantially gastro-insoluble pore former is sodium alginate.

Further aspects of the invention include methods of making the film coating systems described herein, as well as orally ingestible substrates (tablets, caplets, etc.) coated with the enteric coating systems of the invention.

Detailed Description

a) Ethyl cellulose fraction of the dispersion

According to a first aspect of the present invention there is provided an enteric coating system comprising an ethylcellulose dispersion and a substantially gastro-insoluble pore former. The ethylcellulose dispersion of the present invention comprises ethylcellulose which is uniformly dispersed in water with the aid of an emulsifier such as ammonium oleate, the particle size of the ethylcellulose being in the submicron to micron, typically in the range of about 0.1 to 10 microns. The ethylcellulose dispersion may optionally and preferably comprise a plasticizer such as dibutyl sebacate or medium chain triglycerides. Such ethylcellulose dispersions can be prepared according to US patent No.4,502,888, which is incorporated herein by reference. One such ethylcellulose dispersion product can be prepared according to the process disclosed in this patent under the trade name Surelease^®Sold under the name Colorcon of West Point, Pa. According to this embodiment, the ethylcellulose particles are mixed with oleic acid and a plasticizer, and then extruded and melted. Thereafter, the melted plasticized ethylcellulose was directly emulsified in aqueous ammonia under reduced pressure in a high shear mixing device. Ammonium oleate is formed in situ for stabilizing and forming the plasticized dispersion of ethylcellulose particles. Then, purified water is additionally added to obtain a final solid substance. See also U.S. patent No.4,123,403, which is incorporated herein by reference.

In the present inventionIn another aspect of the invention, the ethylcellulose dispersion can also be prepared by: dissolving ethylcellulose in a water-immiscible organic solvent, emulsifying the organic solution in water, optionally with the aid of additives, and removing the organic solvent from the suspension. This process is described in detail in U.S. patent No.4,330,338, which is incorporated herein by reference. One such product is prepared according to the process described in this patent and is sold under the trade name Aquacoat^®ECD, sold by FMC of Philadelphia, PA. However, the plasticizers incorporated into the ethylcellulose dispersion during this preparation are not conventional, and may optionally and preferably be added after the dispersion preparation is complete.

Non-limiting examples of suitable plasticizers for use in the film coating system of the present invention include alkyl carboxylates, polypropylene glycol, castor oil, fractionated coconut oil, dibutyl sebacate, polyethylene glycol, propylene glycol, glycerin, triacetin, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, or mixtures thereof. Preferably, the plasticizer is dibutyl sebacate, medium chain triglycerides such as fractionated coconut oil, or mixtures thereof. The plasticizer may be present in an amount up to about 30% of the ethylcellulose content in the film coating system of the present invention. Preferably, the plasticizer is present in an amount of from about 10% to about 25%, more preferably from about 10% to about 25%, of the ethylcellulose content in the film coating system.

The amount of ethylcellulose included in the film coating system of the present invention depends primarily on the type selected, but for purposes of illustration and not limitation, the concentration of ethylcellulose is generally from about 5% to 30%, most preferably from 7.5% to 20%.

b) Gastric insoluble pore former

The gastro-insoluble pore former included in the film coating system of the present invention may be any pore-forming chemical species known in the art that can be used with ethylcellulose dispersions compatibly, which are substantially insoluble at pH below about 3, but readily soluble at pH above about 5. Preferably, the gastro-insoluble pore former is sodium alginate. Additionally or in addition to sodium alginate, the film coating systems of the present invention may also include alginic acid or other alginates, such as potassium alginate or other deprotonated alginic acids, and salts of monovalent cations. Preferred are low viscosity grades of sodium alginate, especially those having a solution viscosity of less than about 100 centipoise in a 1% aqueous solution. Particularly preferred are the low viscosity sodium alginate grades of Keltone ® LVCR and Manucol ® LB, available from ISP.

The amount of gastro-insoluble pore former included in the film coating system of the present invention will depend primarily on the choice of gastro-insoluble pore former, but for purposes of illustration and not limitation, the sodium alginate concentration will generally be from about 0.5 to 10%, preferably from about 1.0 to 5.0%, most preferably from about 1.5 to 3.5%.

c) Ethyl cellulose: proportion of gastric insoluble pore former

In a most preferred aspect of the invention, the ratio of ethylcellulose to gastro-insoluble pore former in the film coating system ranges from about 1: 1 to about 10: 1. In a preferred aspect, the ratio is from about 3.5: 1 to about 6: 1, while in a more preferred aspect, it is about 4.25: 1.

As previously mentioned, the preferred gastro-insoluble pore former is sodium alginate and the preferred source of ethylcellulose dispersion is Surelease. An example of a film coating system of the present invention comprising these two components would comprise substantially the non-aqueous component of Surelease (nominally 25% solids) to sodium alginate in a preferred ratio of 85: 15 (w/w). Since the nonaqueous components of Surelease include about 75% ethylcellulose, the preferred ratio of ethylcellulose to sodium alginate is 63.75: 15 or about 4.25: 1 (w/w). For the purposes of this description, "solid" refers to all non-aqueous ingredients, including possible plasticizers, which when neat are present in the liquid state.

d) Preferred dispersion solids level

Surelease is a dispersion supplying 25% solids and, in the present invention, is mixed with an aqueous solution containing an appropriate amount of sodium alginate to give the ratios described above. In a preferred aspect of the invention, the final% solids level of the dispersion of the invention is as high as possible without increasing the viscosity of the dispersion to such an extent that the dispersion is difficult to prepare. As can be appreciated by those skilled in the art, it has become recognized that it is difficult to spray the dispersion (regardless of the content) when the viscosity is greater than about 2,000 centipoise (cps). Thus, the final film coating system or dispersion of the present invention has a viscosity of less than about 2,000 cps. Preferably, the dispersion viscosity is from about 100 to about 1,000 cps. The viscosity index increases with increasing sodium alginate content of the dispersion. It is therefore very important to carefully monitor the sodium alginate content and the overall solids level so that it remains within the scope of the present invention as described. Dispersions having a viscosity of less than 100 centipoise can be prepared; however, these dispersions will likely have low total solids levels, which will be disadvantageous in terms of coating processing time. Preferably, the dispersion of the present invention will be applied to tablets or tablet cores at a total solids level of no less than 10% while maintaining the ratio of ethylcellulose and sodium alginate in the preferred range of 1: 1 to 10: 1. Typically, the film coating systems of the present invention are applied at a solids level of from about 10 to about 20%, with a more preferred level of about 15.0%.

e) Auxiliary ingredients

The enteric film coating system may contain a number of additives commonly used in the film collar area. These additives include surfactants, emulsifiers, anti-adherents (detackifiers), glidants, flavoring agents, coloring agents, and the like, and mixtures thereof.

Surfactants and emulsifiers aid in the preparation of stable emulsions. The emulsifier may be an anionic emulsifier, such as sodium lauryl sulfate (USP), a cationic emulsifier such as a quaternary ammonium halide (e.g. cetyl pyridinium chloride) or a non-ionic emulsifier such as a linear fatty alcohol ethylatesor or polyoxyethylene condensate (exemplified by Spans and tweens or polyoxyethylene polypropylene glycols such as Pluronic F68, sold by BASF corp. Other agents are also used to perform these functions, including materials such as fatty acid polyglycerol esters, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monooleate, propylene glycol mono-or diesters of fatty and fatty acids, sodium lauryl sulfate, and sorbitan monostearate. In general, the emulsions and latexes of the invention can be prepared without the use of surfactants or emulsifiers, but in most cases, the use of these additives results in good particle size and better stability. The biodegradable polymers listed above form emulsions and produce latexes without the benefit of additives.

A variety of other additives may advantageously be included in the dispersion to enhance its properties, such as cetyl alcohol, beeswax, (yellow, bleached or white and natural white), candelilla wax, carnauba wax, cocoa butter, fatty acids such as stearic acid, monoglycerides, diglycerides and triglycerides (including glyceryl monostearate, glyceryl monooleate and the like and self-emulsifying glyceryl monostearate), glyceryl lactylate, oleate or palmitate (other self-emulsifying waxes), fatty acid glyceryl lactylate (also self-emulsifying) lauric, lauryl, linoleic, caprylic and acetic esters and paraffin waxes. High amounts of additives such as carnauba wax and chlorowax improve the appearance of the tablet coating. Of course, these may be added to the system as a polishing agent.

The emulsifier and surfactant comprise about 0.1% to 10% by weight of the film coating system. More preferably, the emulsifier is from about 0.3% to 6% by weight of the system, and most preferably, it is from 0.5% to about 3.5% by weight.

Flavoring agents, which are primarily used to mask taste and/or odor, may be vanillin, sodium citrate, citric acid, mint, orange, lemon oil, or other pharmaceutically approved flavoring or masking agents and combinations thereof.

The colorant may be FD & and D & C lakes, titanium dioxide, iron oxides, natural pigments, pearlescent agents, or dyes approved for ingestion by the u.s.federal Drug Administration, or combinations thereof. Preferably, the colorant is present in an amount of about 0.01% to about 30% by weight of the system. For Surelease to be included in the system, the colorant should be any of the above colorants that are stable at the pH of the dispersion (about 10).

g) Method for producing film coating systems dispersions

According to another aspect of the invention, there is provided a method of making a film coating system of the invention. The method comprises providing and preparing an aqueous dispersion of ethylcellulose particles (having the particle size distribution described above), and mixing the dispersion with a solution comprising a gastro-insoluble pore former. The mixture is mixed with a suitable mixer, such as a propeller mixer, until a substantially homogeneous dispersion is obtained. In a preferred aspect of the invention, the enteric dispersion of the invention is prepared by the following process: a solution containing the gastro-insoluble pore former sodium alginate is prepared by adding a suitable sodium alginate, such as Manucol LB, to a suitable amount of distilled water to form an approximately 5% solution, and stirring the composition with a propeller-type stirrer for a sufficient time until the sodium alginate is completely dissolved and uniformly dispersed in the water. To this solution was added a fully formulated ethylcellulose dispersion under the trademark Surelease containing a plasticizer. The resulting dispersion is gently mixed for a sufficient time until a uniform coating dispersion is obtained, preferably having a solids content of about 10-20% and a viscosity of 100-.

The adjunct ingredients may be added in a variety of ways. First, the adjunct ingredients are added to the gastro-insoluble pore former prior to dispersion in water. In this case, preferably, the adjunct ingredients are pre-mixed with the gastro-insoluble pore former to obtain a homogeneous mixture prior to the addition of water. Second, the adjunct ingredients are added continuously to the stirred aqueous solution of the gastro-insoluble pore former prior to the addition of the ethylcellulose dispersion, ensuring uniform dispersion of the adjunct ingredients. Third, the adjunct ingredient may be added to the ethylcellulose dispersion before the aqueous solution of the gastric insoluble pore former is added to the dispersion to ensure uniform dispersion of the adjunct ingredient. Fourth and finally, after the gastro-insoluble pore former and the ethylcellulose dispersion are mixed, the adjunct ingredients may be added to their mixture. Again, care was taken to ensure that all ingredients were mixed uniformly.

h) Administration of tablet cores

According to another aspect of the invention, there is provided a method of coating an orally ingestible substrate with a system comprising an enteric film coating as described herein. The method comprises applying an enteric film coating system described herein to a substrate, such as an orally ingestible substrate. Non-limiting examples of suitable substrates that may be coated with the coating system of the present invention include compressed tablets, caplets, cores containing pharmaceutical, nutraceutical, and food supplements, and other oral ingestion cores known in the art. Garlic tablets and soft gelatin capsules containing fish oil are examples of suitable orally ingestible substrates. Preferably, the enteric film coating system is applied to the tablet or other core until a weight gain of about 0.5% to about 20% is achieved. More preferably, the weight gain is from about 2% to about 10%, yet most preferably, the weight gain is from about 4% to about 8%. Preferably, the coating is carried out using a coating tablet or multiparticulate process known in the art.

In another aspect of the invention, the tablet core is coated with a barrier coating to increase the weight gain by up to about 3% by weight prior to application of the enteric coating of the invention. The purpose of the barrier coat is to improve the mechanical strength of the tablet core and to act as a barrier between the matrix and the top coat to prevent possible interactions between the matrix and the enteric top coat. Suitable barrier coatings include those coatings which do not substantially delay the release of the active ingredient formulation from the core. Non-limiting examples of these immediate release film coating systems are Opadry ®, Opadry II, Opadry NS, and Opaglos ® 2, available from Colorcon.

Examples

The following examples are presented to further illustrate the invention but are not meant to limit the scope of the invention in any way.

The following materials were used in the examples of the present invention:

material	Function(s)	Suppliers of goods
			Surelease®(ethylcellulose content: 18.8%) (Medium chain triglyceride content: 4%, 21.3% relative to ethylcellulose) (25% solids w/w)	Film forming agent	Colorcon
Sodium alginate a) Manucol LBb) Keltone LVCR	Film/pore former 1% solution 4cP 1% solution 50cP	ISP Alginates
			Opadry®NS Clear	Film forming/barrier layer	Colorcon
Opadry®Clear	Membrane/pore former	Colorcon

Tablet core

Garlic Core A-11.2 mm standard concave circle (total weight 545 mg)

Garlic Core B-19.2-mm capsule tablet (875 mg total weight)

Example 1

a) Composition of matter

Garlic coats (1.0Kg total Core A) were sequentially coated with a barrier coat dispersion from Opadry and from an enteric coat dispersion of the composition of the invention^®NS Clear coating composition.

First, an Opadry NS barrier coating dispersion was prepared by adding an Opadry NS formulation (30 grams) to distilled water (345 grams) and stirring the mixture for 45 minutes using a propeller stirrer. The resulting dispersion was homogeneous, yellow-brown. Coating the dispersion onto a tablet produces a theoretical weight gain of 30 grams per 1,000 grams or 3%.

The enteric dispersion of the present invention is prepared as follows. The sodium alginate solution was prepared by adding Manucol LB (12 g) to distilled water (249.33 g) and stirring the mixture for 45 minutes using a propeller stirrer. The resulting solution was opaque, yellow-brown. Surelease (272 g) was added to the solution and the resulting dispersion was gently mixed with a propeller stirrer for 30 minutes. Since Surelease contains 25% (w/w) of non-aqueous or "dry" ingredients, the content of non-aqueous ingredients added to the resulting mixture from Surelease dispersion was 68 g. Thus, the relative ratio of the non-aqueous Surelease ingredient to sodium alginate was 68: 12 g or 85% to 15% (w/w). The final coating dispersion had a dispersion solids content of 533.33 grams of the non-water ingredients in the total coating dispersion, or about 15% solids. The final coating dispersion was opaque, beige in color, maintaining a viscosity of 378 cps at room temperature (Brookfield viscometer, spindle 2, 20 r.p.m.).

b) Application method

The tablet cores (Garlic Core a, 1.0kg quantity) were added to a fully perforated, side vented coating pan (1 kg capacity) equipped with a Cole-Parmer Masterflex pump containing a pump head, silicone tubing and an air assisted spray nozzle. The core was coated sequentially with an Opadry NS barrier layer (3% theoretical weight gain, 8% solids) and the coating dispersion of the invention under the following treatment conditions:

c) coating parameters-isolation layer and enteric layer

Parameter(s)	Insulating layer	Enteric layer
			Intake air temperature (. degree. C.)	57	57
Exhaust temperature (. degree. C.)	44	44
			Product temperature (. degree.C.)	43	41
Fluid feed rate (g/min.)	12	12
			Atomization pressure (psi)	25	30
Mode (Pattern) air pressure (psi)	25	30
			Volume of dry air (cfm)	120	120
Pan rotating speed (rpm)	15	16
			Treatment time (minutes)	28	37

Samples with 4, 6 and 8% weight gain of the enteric layer were removed from the coating pan for analysis.

d) Analytical method

Six tablets were subjected to disintegration analysis in hydrochloric acid (0.1N) for 1 hour. After this period, the tablets were removed from the disintegration tank and the cabinet was inspected for cracking, flaking, swelling or film rupture. The identification result by "pass" indicates that six tablets showed no cracking, flaking, swelling or film cracking.

After testing in 0.1N HCl, the tablets were placed directly in phosphate buffer at pH6.8 and the disintegration time was examined. The results are reported as the average time required for the core (garlic core) to disintegrate completely.

Disintegration results-example 1

Theoretical weight gain	Intestinal disintegration	pH6.8 buffer disintegration time (min: sec)
			Garlic Core A	Not applicable to	40:42+/-5:14
4％	By passing	71:54+/-13:48
			6％	By passing	87:30+/-8:30
8％	By passing	95:30+/-4:52

Examples 2 to 4

Examples 2-4 are compositions of the present invention prepared in a manner similar to that described in example 1, with minor adjustments to the composition or method of application, as described in the following table.

In examples 2-4, the appearance and structure of the final dosage form was similar to the properties of the dosage form in example 1. The difference in example 2 was noted, where the ratio of Surelease solid to sodium alginate in example 2 was 75/25, requiring a higher weight gain of the enteric layer to achieve enteric protection. Moreover, a higher sodium alginate content provides a faster disintegration time in ph6.8 buffer and at an equal weight gain compared to example 1.

Thus, examples 3-4 show that higher viscosity and higher molecular weight grades of sodium alginate can be successfully used in the compositions of the present invention; however, it is desirable to use a higher viscosity grade of sodium alginate so that dispersions of low solids content can be prepared, ensuring that they are sufficiently low viscosity to be easily sprayed onto tablets.

Comparative data sheet-examples 2 to 4

Weight in Dispersion (g)

Composition (I)	Example 2	Example 3	Example 4
				Surelease (same as example 1) Keltone LVCR sodium alginate 50 cPhanucol LB	24020	27212	27212

Sodium alginate 4cP additional Total Dispersion (grams) Core type Garlic Core AGallic Core B barrier coat (if applied) Opadry NS Clear Dry solids content (%) Dispersion viscosity (cP)

273.3533.3××15％690

356.0640××12.5％1550

356.0640×12.5％1550

Disintegration results-examples 2 to 4

Theoretical weight gain	Intestinal disintegration	Disintegration time in pH6.8 buffer (min: sec)
			Garlic Core B	Not applicable to	55:12
Example 2 to 8%	By passing	62:00+/-4:34
			Example 3-4%	By passing	98:12+/-5:57
Example 4-4%	By passing	97:24+/-8:17

Examples 5 to 6

Examples 5-6 comparative compositions and dispersions were prepared in a similar manner to that described in example 1, with minor adjustments to the composition or method of application, as described in the table below.

In examples 5-6, the difference in disintegration time was recorded in a buffer at pH 6.8. Inclusion of OpadryClear in an enteric film coating system significantly increases disintegration time to a point where these coated dosage forms would be considered unsuitable for human consumption. This indicates that sodium alginate allows pores to be created through which the surrounding medium or active ingredient can migrate more effectively than hydroxypropyl methylcellulose based film coating systems.

Comparative data sheet-examples 5 to 6

Weight in Dispersion (g)

Composition (I)	Example 5	Example 6
			Surelease E-7-19010 (same as example 1) Opadry Clear additional Total Water Dispersion (g) Core type Garlic Core B barrier coat (if applicable) Opadry NS Clear Dry solids content (%) Dispersion viscosity (cP)	27212516800×10％44	27212516800××1O％44

Disintegration results-examples 5 to 6

Theoretical weight gain	Intestinal disintegration	pH6.8 buffer disintegration time (minutes: seconds)
			Example 5-4%	By passing	> 300 minutes
Example 6-4%	By passing	> 300 minutes

Claims (25)

1. An enteric film coating system comprising an ethylcellulose dispersion and a substantially gastro-insoluble pore former.

2. The enteric film coating system of claim 1, wherein the substantially gastro-insoluble pore former is sodium alginate.

3. The enteric film coating system of claim 1, wherein the ratio of ethylcellulose in said ethylcellulose dispersion to gastro-insoluble pore former is from about 1: 1 to about 10: 1.

4. The enteric film coating system of claim 3, wherein the ratio of ethylcellulose in said ethylcellulose dispersion to gastro-insoluble pore former is from about 3.5: 1 to about 6: 1.

5. The enteric film coating system of claim 4, wherein the ratio of ethylcellulose in said ethylcellulose dispersion to gastro-insoluble pore former is about 4.25: 1.

6. The enteric film coating system of claim 1, wherein the ethylcellulose dispersion comprises plasticized ethylcellulose particles.

7. The enteric film coating system of claim 1, wherein the ethylcellulose particles in said ethylcellulose dispersion have an average particle size of from about 0.1 to about 10 microns.

8. The enteric film coating system of claim 1, further comprising a plasticizer.

9. The enteric film coating system of claim 8, wherein the plasticizer is selected from the group consisting of dibutyl sebacate, medium chain triglycerides, and mixtures thereof.

10. The enteric film coating system of claim 8, wherein the plasticizer is present in an amount up to about 30% of the amount of ethylcellulose.

11. The enteric film coating system of claim 10, wherein the plasticizer is present in an amount of about 15% to about 25% of the amount of ethylcellulose.

12. The enteric film coating system of claim 1, wherein the viscosity is less than about 2,000 centipoise.

13. The enteric film coating system of claim 12, wherein the viscosity is from about 100 to about 1,000 centipoise.

14. The enteric film coating system of claim 2, wherein the concentration of sodium alginate is from about 0.5 to about 10%.

15. The enteric film coating system of claim 14, wherein the concentration of sodium alginate is from about 1.0 to about 5.0%.

16. The enteric film coating system of claim 15, wherein the concentration of sodium alginate is from about 1.5 to about 3.5%.

17. The enteric film coating system of claim 1, wherein the total solids level is at least about 10%.

18. The enteric film coating system of claim 17, wherein the total solids level is from about 10 to about 20%.

19. The enteric film coating system of claim 1, further comprising an ingredient selected from the group consisting of emulsifiers, anti-adherents, surfactants, glidants, flavoring agents, coloring agents, and mixtures thereof.

20. An orally-ingestible substrate coated with the enteric film coating system of claim 1.

21. The orally-ingestible substrate of claim 20, further comprising a barrier coat.

22. The orally-ingestible substrate of claim 20, wherein the enteric film coating system is applied in an amount of from about 0.5 to about 20% weight gain.

23. The orally-ingestible substrate of claim 22, wherein the enteric film coating system is applied in an amount of about 4 to about 8% weight gain.

24. A method of coating an orally-ingestible substrate with an enteric film coating, comprising applying the enteric film coating system of claim 1 to the orally-ingestible substrate.

25. The method of claim 24, further comprising the step of applying a barrier coat prior to applying the enteric film coating system.