WO2006111981A2

WO2006111981A2 - Film coating compositions and methods providing moisture barrier

Info

Publication number: WO2006111981A2
Application number: PCT/IN2005/000144
Authority: WO
Inventors: Chetan Rajsharad; Shivaji Kamble
Original assignee: Ideal Cures Pvt. Ltd
Priority date: 2005-04-20
Filing date: 2005-05-04
Publication date: 2006-10-26
Also published as: WO2006111981A3

Abstract

A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets and the like comprises polyvinyl alcohol, self emulsifying glyceryl monostearate, and optionally a flow aid, a colorant, a plasticizer, a flavoring agent and/or a sweetening agent. A liquid coating solution or dispersion for forming a moisture barrier film coating for pharmaceutical tablets and the like comprises polyvinyl alcohol, self emulsifying glyceryl monostearate, water, and optionally a flow aid, a colorant, a plasticizer, a flavoring agent and nor a sweetening agent. A method of coating pharmaceutical tablets and the like with a moisture barrier film coating comprises forming a liquid coating solution or dispersion for forming a moisture barrier film coating for pharmaceutical tablets and the like comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, and optionally a flow aid, a colorant, a plasticizer, a flavoring agent and/or a sweetening agent, applying the coating solution or dispersion onto the tablets to form a film coating on the tablets, and drying the film coating on the tablets.

Description

FILM COATING COMPOSITIONS AND METHODS PROVIDING MQISIURE

BARRIER

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention is in the field of coating of pharmaceutical substrates like tablets and the like and is specifically addressed to coatings capable of providing / acting as a moisture barrier.

2. Description of the Prior Art

Many therapeutic ingredients and dosage forms into which they are formulated undergo degradation due to contact with moisture which has been adsorbed from the atmosphere. To combat this degradation, it is frequently necessary for such moisture sensitive therapeutic ingredients or dosage forms to be packed in moisture resistant or moisture impermeable special containers to limit their exposure to atmospheric moisture.

The climatic conditions vary in different parts of the world and in areas having humidity, specialized packaging is not a solution to moisture degradation. In case of solid dosage forms such as tablets, capsules and granules, the need for special packaging or augmentation of moisture protection provided by such packaging may be achieved by coating them with materials which reduce the rate at which such substrates or dosage forms absorb atmospheric moisture. Such moisture barrier coatings are known. Traditionally, water insoluble polymers, dissolved in an organic solvent have been used to achieve a moisture barrier coating. However the disadvantages with this resides in the need to use an organic solvent or the difficulty in application of these difficult aqueous polymer dispersions and the reduced aqueous solubility of the coating leading to prolongation of disintegration times of the dosage form during stability and when ingested by a person. The delay or prolongation in disintegration time may also delay the therapeutic action of the active ingredient. The use of the polymer polyvinyl alcohol, PVA, as a moisture barrier coating has been previously suggested. However the polymer grades which go fast into solution, thus enabling formation of a film coating dispersion / solution have an inherent disadvantage of being sticky. In addition one needs a plasticizer along with the PVA, which helps the formation of a coat by providing a degree of plasticity to the coat without compromising on the moisture barrier properties of the final coat. Earlier dry moisture barrier coating compositions as disclosed by US 5885617 use Soya lecithin that acts as an anti-tack agents and also as a plasticizer for the moisture barrier coat. However there are certain disadvantages of Soya lecithin. Soya lecithin being highly hygroscopic, tends to pick up moisture, hence the material stability is very poor with low shelf life. It also tends to become pale yellow to dark yellow on storage, thus interfering with the color shade of the final product. The coating formulation containing Soya lecithin, if not stored properly are likely to pick moisture from atmosphere and color shade may also change.

SUMMARY OF THE INVENTION

A dry powder moisture barrier coating composition capable of forming a moisture barrier film coat for pharmaceutical substrates like tablets and the like comprising polyvinyl alcohol in combination with self emulsifying glyceryl monostearate, together with none, one or more of the following components which enhances the desirable coating characteristics of the resulting film coating: a flow aid, a colorant, a plasticizing agent, a flavoring agent and a sweetening agent.

A method of preparing the moisture barrier film coating powder composition of the invention comprises the steps of mixing polyvinyl alcohol with self emulsifying glyceryl monostearate and optionally with one or more of the following components, until a dry homogenous powder mixture is produced: a flow aid, a colorant, a plasticizing agent, a flavoring agent and a sweetening agent.

Preferably the mixture of polyvinyl alcohol and self emulsifying glyceryl monostearate and any of the following components, if any of the components is to be included in the coating composition, is milled: a flow aid, a colorant a plasticizing agent, a flavoring agent and a sweetening agent. The resultant dry powder coating composition is readily soluble or dispersible in hot water to form a liquid coating solution or dispersion that is ready to use within 45 minutes.

Alternatively, the dry moisture barrier film coating composition may be produced by producing a mixture of ingredients processed into a granular form to form a granular coating composition by using the known methods of wet granulation, fluid bed granulation, spray granulation and dry compaction, roller compaction or slugging. The invention also embodies a liquid coating dispersion / solution for forming a moisture barrier film coat comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, an optional flow aid, an optional colorant, an optional plasticizer, an optional flavoring agent and an optional sweetening agent is mixed into hot water. The procedure for making the liquid coating dispersion of the invention comprises dispersing the dry powder coating composition, the granular coating composition, or the individual ingredients of the coating composition separately, into hot water and /or milling and /or stirring until a homogenous mixture of a desired viscosity is produced.

PVA is available in a number of grades some of which are soluble in hot water whereas the others are soluble in cold water. The hot water soluble grades of PVA offer excellent moisture barrier properties compared to the cold water-soluble grades. As the method of making the coating dispersion in the present invention involves the use of hot water, the present invention may comprise of polyvinyl alcohol of either grade, as the polyvinyl alcohol shall fully dissolve in the hot water used. Any grade of PVA may be used depending upon the extent of the moisture barrier protection required, depending on the pharmaceutical substrate or dosage form.

The glyceryl monostearate, which may be of self emulsifying grade manufactured by Sasol and sold under the trade name Imwitor^R, available commercially in the form of flakes, acts as an anti-tack agent and as a plasticizer in the present invention. Glyceryl monostearte has been quite popularly used as an emulsifier in the food industry. It is also referred to as monostearin and is a mixture of varying proportions of glyceryl monostearate, glyceryl monopalmitate and glycerin esters of fatty acids. It is prepared by glycerolysis of certain fats / oils that are derived from edible sources or by esterification with glycerol of stearic acid derived from edible sources. The use of glyceryl monostearate has been as an emulsifier both in the food as well as pharmaceutical industry. It has never been used as an anti-tack agent or its use as a plasticizer in pharmaceutical film coatings has not been reported. In order to achieve better film properties, use of a plasticizer like glycerin, PEG 6000, PEG 400, triethyl citrate, propylene glycol or triacetin or a mixture of plasticizers is recommended. The present inventors have surprisingly and unexpectantly found that self- emulsifying glyceryl monostearate functions as an anti-tack agent and as a plasticizer by locking moisture in the coating so the coating stays flexible and not brittle. Surprisingly, this locked-in moisture in the coating, while contributing to the plasticizing effect, does not compromise on the moisture barrier properties of the overall coating.

The colorant may be any FDA approved colors, opacifiers or dyes like iron oxides, titanium dioxide, aluminum lakes or natural colors. Talc, fumed silica, starch or lactose may be used as a flow aid.

The optional plasticizer additionally required for better film properties might include glycerin, PEG 6000, PEG 400, triethyl citrate, propylene glycol or triacetin or a mixture of these.

The flavoring agent used may include strawberry or mint flavors. Sweetening agents include sucrose, aspartame, sodium saccharin and the like. An essential feature of this invention is the use of hot water for reconstituting the dry moisture barrier coating composition. The glyceryl monostearte can function as an anti-tack agent and as a plasticizer only after it melts. Thus once the glyceryl monostearate and the PVA go into solution the glyceryl monostearate emulsifies and functions as an anti-tack agent and as a plasticizer. In addition by virtue of the emulsifying property it also helps to keep the hot water soluble grades of PVA in solution. After cooling of the reconstituted film coating dispersion / solution it does not allow the PVA to come out and it neither comes out by itself. By no reason are the properties of the film coating dispersion / solution lost because of the cooling effect over a period of time. The ranges for each component of the dry coating compositions of the invention are as follows, by weight:

The ranges for each component of the liquid coating dispersions of the inventions are as follows, by weight.

DETAILED DESCRITTON

We now provide examples to illustrate the invention, all ingredients by weight

Example 1 :

440 grams of polyvinyl alcohol, 150 grams of talc, 100 grams of titanium dioxide_^ 30 grams of lake sunset yellow, 80 grams of PEG 6000, and 200 grams of self emulsifying glyceryl monostearate are loaded into a dry powder blender/mill, and vigorously mixed therein for at least 5 minutes or until a homogenous mix is achieved, resulting in one formulation of the inventive dry powder moisture barrier film coating composition. 500 grams of this formulation of the inventive dry powder moisture barrier film coating composition is dispersed in 2000 grams of hot purified water at a temperature of about 75°C to 90⁰C to form an aqueous suspension of the invention. Specifically, 2000 grams of purified water at a temperature of about 90⁰C, is loaded into a vessel having a diameter that is approximately equal to the depth of the final suspension. A low shear mixer, preferably having a mixing head that has a diameter that is approximately 1/3 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 just above the mixing head without any air being drawn into the water. Then, the 500 grams of the moisture barrier film coating powder composition is added to the vortex at a rate where there is no excessive build up of dry powder. The temperature of the hot purified water is maintained at 9O⁰C before addition and then at around 85⁰C till the glyceryl monostearate melts and goes into solution to form a suspended solution / dispersion. The speed or depth of the mixing head is adjusted to avoid air being drawn into the suspension so as to avoid foaming. The suspension is stirred for 45 minutes and is then ready for spraying onto substrates like pharmaceutical tablets.

In this Example 1, 10 Kg of tablets are coated with the coating of the invention so as to obtain about a 3.0% weight gain. The extra 100 grams of the dry powder moisture barrier film coating composition above the 300 grams of the dry powder moisture barrier film coating composition needed to obtain a 3.0% weight gain on the tablets is included to allow for losses of coating composition during the coating procedure. 10 Kg of tablets which have logos embossed therein are loaded into a coater, and the tablets are rotated in the coater at a rotation speed of 10-15 rpm. The tablets are sprayed with the coating suspension of this Example 1 while the tablets are being rotated. Hot air at 60 to 7O⁰C, is used to evaporate the water in sprayed coating suspension and to maintain the tablets at 38 to 42°C. Upon completion of the coating process, the tablets show a smooth surface with excellent logo definition.

In the following Examples 2 to 14, one Kg batches of coating suspension are produced by mixing 200 grams of inventive dry powder moisture barrier coating composition into 800 grams of purified water. These coating suspensions are then sprayed onto tablets. The procedures set out in Example 1 for making the dry powder moisture barrier coating composition, for making the coating suspension, and for spraying the coating suspension onto tablets are used in Examples 2 to 49. The coated tablets of the Examples 2 to 49 show a smooth surface with excellent logo definition Example 2

Example 6

Example 8

\

Example 13

Example 14

Example 15

Example 18

Example 23

Example 24

Example 25

Example 26

Example 27

Example 30

Example 31

Example 36

Example 45

Example 48

Component Percentage Grams

Polyvinyl Alcohol 44 440

Triethyl citrate 8 80

Self emulsifying glyceryl monostearate 22 220

Titanium dioxide 10 100

Mint flavor 16 160 '

Total 100-% iooa

Example 49

Component Percentage Grams

Polyvinyl Alcohol 44 440

Triethyl citrate 8 80

Self emulsifying glyceryl monostearate 22 220

Titanium dioxide 5 50

Lake Ponceau 4R 5 50

Asparatme 16 160

Total 100 % 1000

Example 50

Component Grams

Polyvinyl alcohol 440

Self emulsifying Glyceryl monostearate 200

Talc 150

Titanium dioxide 130

PEG 6000 80

Water 4000

Total 50000 I

The coating dispersion of this Example 50 is made and used using the procedures set out in Example 1 It was unexpectedly found that glyceryl monostearate which is used as an emulsifier commonly had tack reduction properties and also acted as a plasticizer by locking moisture in the coating as to keep the coating flexible and not brittle. It is also unexpected that this moisture while contributing to plasticization, does not compromise the moisture barrier properties of the overall coating.

This invention provides the means of preparing a moisture barrier coating for application to pharmaceutical solid dosage forms in which the coating composition material is presented as a dry particle powder or granular powder which is readily dispersible in hot water. The resultant coating solution or dispersion is ready to use by applying it to tablets within 45 minutes. The coating solution or dispersion may also be presented in the form of a ready-to-use liquid, or liquid concentrate, which is diluted prior to use.

Compared with existing moisture barrier coatings using water insoluble polymers, there is negligible effect on the disintegration time of the coated dosage forms coated with the inventive coating.

The dry form of the invention is manufactured using rotary mixers or mills. The ingredients are loaded and then blended/milled until a homogenous mix is produced. In the case of liquid dispersions, the ingredients are dispersed into hot or cold water and stirred or milled until a homogenous dispersion or solution of the desired correct viscosity is produced.

The dry form of the invention, which comprises a powder of PVA and self emulsifying glyceryl monostearate, and optionally a flow aid, a colorant, and a plasticizer, is dispersed in hot water and stirred till the self emulsifying glyceryl monostearate melts and until the PVA is hydrated and a homogenous mixture is produced. The liquid solution or dispersion formed, which comprises PVA, self-emulsifying glyceryl monostearate, and any optional components mixed into hot water, may be ready-to-use. The resulting coating dispersion is sprayed onto the dosage forms using airless or airborne methods. The movement of air around or through the tablet bed facilitates drying of the film on the tablet surface.

Claims

CLAIMS:We claim:

1. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical substrates comprising: polyvinyl alcohol, self-emulsifying glyceryl monosterate and water.

2. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monosterate, water, and a plasticizer, the water being in a range of about 60.0% to about 95.0% by weight of the composition, preferably the water being in a range of about 75.0% to about 85.0% by weight of the composition.

3. A pharmaceutical tablet coated with a moisture barrier film coating made using a dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monosterate, a flow aid, a colorant, a plasticizer, a flavoring agent and a sweetening agent.

4. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, and self emulsifying glyceryl monostearate, the polyvinyl alcohol being in a range of about 20.0% to about 99.0% by weight of the composition, and the self emulsifying glyceryl monostearate being in a range of about 5.0% to about 50% by weight of the composition.

5. The coating composition of claim 4, the polyvinyl alcohol being in a range of about 30.0% to about 98.0% by weight of the composition, and the self emulsifying glyceryl monostearate being in a range of about 10.0% to about 40.0% by weight of the composition.

6. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, and a flow aid, the flow aid being in a range of greater than 0.0% to about 40.0% by weight of the composition preferably in a range of about 15.0% to about 25% by weight of the composition.

7. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, and a flow aid, the flow aid being talc, fumed silica, lactose, or starch.

8. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, and a colorant, the colorant being in a range of 0.0% to about 60.0% by weight of the composition, preferably in a range of about 25.0% to about 40.0% by weight of the composition for the colored compositions.

9. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self-emulsifying glyceryl monostearate, and a colorant, the colorant being any food approved colors, opacifiers or dyes.

10. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, and a plasticizer, the plasticizer being in a range of greater than 0.0% to about 30.0% by weight of the composition, preferably in a range of about 2.0% to about 30.0% by weight of the composition.

1 1. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, and a plasticizer, the plasticizer being glycerin, polyethylene glycol molecular weight varying from 200 to 8000, triethyl citrate, propylene glycol, triacetin or combinations thereof and the like.

12. The coating composition of claim 4, the self emulsifying glyceryl monostearate being in a range of about at least 10.0% further including a flow aid, the flow aid being in a range of about 0% to about 25% by weight of the composition, the flow aid being talc, fumed silica, lactose, or starch, a colorant, the colorant being in a range of about 0.0% to about 40.0% by weight of the composition, the colorant being any food approved colors, opacifiers, or dyes, a plasticizer, the plasticizer being in a range of about 2.0% to about 30.0% by weight of the composition, the plasticizer being glycerin, polyethylene glycol molecular weight varying from 200 to 8000, triethyl citrate, propylene glycol, triacetin or combinations thereof, a flavoring agent being in a range of about 0.0% to about 10.0% by weight of the composition, a sweetening agent being in a range of about 0.0% to about 6.0% by weight of the composition, the sweetening agent being aspartame, sodium saccharin , sucrose or a combination thereof.

13. A method of coating substrates with a moisture barrier film coating, comprising mixing the coating composition according to claim 4 into hot water to form an aqueous coating solution/dispersion, applying the coating solution / suspension onto the substrates to form a film coating on the substrates, and drying the film coating on said substrates.

14. A pharmaceutical tablet coated with a moisture barrier film coating made using the coating composition according to claim 12.

15. A method of coating substrates with a moisture barrier film coating, comprising mixing the coating composition according to claim 13 into hot water to form an aqueous coating solution/dispersion, applying the coating solution / suspension onto the substrates to form a film coating on the substrates, and drying the film coating on said substrates.

16. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, and self emulsifying glyceryl monostearate, the polyvinyl alcohol being in a range of about 20.0% to about 98.0% by weight of the composition.

17. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, and self emulsifying glyceryl monostearate, the self emulsifying glyceryl monostearate being in a range of about 10.0% to about 40.0% by weight of the composition.

18. A coated substrate made in accordance witlvthe method of claim 13.

19. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol^ self emulsifying glyceryl monostearate, and water, the polyvinyl alcohol being in a range of about 5.0% to about 40.0% by weight of the composition, and the self emulsifying glyceryl monostearate being in a range of about 10.0% to about 40.0% by weight of the composition.

20. The liquid composition of claim 19, the polyvinyl alcohol being in a range of about 2.0% to about 28.0% by weight of the composition, and the self emulsifying glyceryl monostearate being in a range of about 1.0% to about 7.0% by weight of the composition.

21. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, and a flow aid, the flow aid being in a range of greater than 0.0% to about 16.0% by weight of the composition preferably in a range of about 3.0% to about 5.0% by weight of the composition.

22. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, and a flow aid, the flow aid being talc, fumed silica, lactose, or starch.

23. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, and a colorant, the colorant being in a range of 0.0% to about 24.0% by weight of the composition preferably in a range of about 4.8% to about 8.0% by weight of the composition.

24. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self-emulsifying glyceryl monostearate,. water, and a colorant, the colorant being any food approved colors, opacifiers or dyes.

25. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, and a plasticizer, the plasticizer being in a range of greater than 0.0% to about 40.0% by weight of the composition preferably in a range of about 2.0% to about 30.0% by weight of the composition.

26. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, a flow aid, a colorant, a plasticizer and a flavoring agent, the flavoring agent being in a range of greater than 0.0% to about 25.0% by weight of the composition preferably in a range of about 0.1% to about 20.0% by weight of the composition.

27. The composition of claim 26, the flavoring agent being strawberry flavor, mint flavor, vanilla flavor and the like or a combination of flavors.

28. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, a flow aid, a colorant, a plasticizer and a flavoring agent, the flavoring agent being in a range of greater than 0.0% to about 6.0% by weight of the composition.

29. A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, a flow aid, a colorant, a plasticizer a flavoring agent, and a sweetening agent, the sweetening agent being in a range of 0.0% to about 25.0% by weight of the composition preferably in a range of about 0.0% to about 10.0% by weight of the composition.

30. The composition of claim 29, the sweetening agent being aspartame, sodium saccharin, sucrose and the like or a combination thereof.

31. A liquid moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets comprising polyvinyl alcohol, self emulsifying glyceryl monostearate, water, a flow aid, a colorant, a plasticizer, a flavoring agent, and a sweetening agent, the sweetening agent being in a range of 0.0% to about 6.0% by weight of the composition.