Kollicoat Mae Grades

Technical Information

Kollicoat ® MAE grades

April 2006 Spersedes issue dated May 2005 MEMP 030725e-02/Page 1 of 12

® = Registered trademark of BASF Aktiengesellschaft

Methacrylic acid/ethyl acrylate copolymers for enteric coatings



Excipients s Contract Manufacturing Value Added

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Kollicoat® MAE grades

Contents Page

1.

Introduction

3

1.1 General

3

1.2 Structural formula

3

1.3 Trivial names

3

1.4 Commercial form

3

2.

3

Specifications and properties

2.1 Description

3

2.2 Physicochemical properties

3

2.3 Pharmacopoeia

4

3.

4

Application and examples of formulations

3.1 Processing instructions

4

3.2 Coloured enteric film coatings for tablets

6

3.3 Coloured enteric film coatings for pellets and crystals

8

3.4 White enteric film coatings for pellets

9

3.5 Colourless enteric coatings for soft gelatin capsules

10

3.6 Subcoating of cores prior to sugar-coating

11

3.7 Further applications

11

3.8 Patents

11

4.

Storage

11

5.

Shelf life

11

6.

PBG Number

11

7.

Packaging

11

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Kollicoat® MAE grades

1. Introduction 1.1 General

Kollicoat® MAE 30 DP and Kollicoat® MAE 100P are copolymers derived from methacrylic acid/ethyl acrylate and are used as film-formers in the pharmaceutical industry for the production of enteric coatings for solid dosage forms.

1.2 Structural formula

 

  The ratio of the components in the copolymer is roughly 1 : 1. The Kollicoat® MAE grades have an anionic character. The average molecular weight Mw is of the order of 250,000.

Kollicoat® MAE 100P has been treated with sodium hydroxide to neutralize about 6 mol-% of the carboxyl groups.

1.3 Trivial names

Methacrylic Acid Copolymer Type C (USP), Methacrylic Acid Copolymer LD (JPE) and Methacrylic Acid-Ethyl Acrylate Copolymer (Ph. Eur.), Methacrylsäure Copolymer.

1.4 Product form

Kollicoat® MAE 30 DP is an aqueous dispersion with a solids content of 30%. The milky white, low-viscosity product has a faint, characteristic odour.



Kollicoat® MAE 100P is a white redispersible powder with a faint characteristic odour. The neutralized carboxyl groups in the powder make it easy to redisperse in water without further auxiliaries. The properties and processing requirements of latices produced with it are the same as those of Kollicoat® MAE 30 DP, from which it is manufactured.

2. Specifications and properties 2.1 Description

The Kollicoat® MAE grades contain 0.7% sodium lauryl sulfate (USP) and 2.3% Polysorbate 80 (Ph. Eur.) as emulsifying agents. (The percentages refer to the solid substances.) The fatty acids used in the manufacture of Polysorbate 80 are of vegetable origin. The Kollicoat® MAE grades are weakly acidic copolymers that dissolve at a pH above 5.5.

2.2 Physicochemical properties

Kollicoat® MAE 30 DP Kollicoat® MAE 100P Identity Apearance of the Film Viscosity Coagulate content Acid value DIN 53402

conforms conforms <15 mPas <1.0% 300 – 330 mg KOH per g of dry substance Methacrylic acid, % 46.0 – 50.6 pH 2.0 – 3.0 Specific gravity (DIN 53217) 1.062 –1.072 Microbiological status conforms Solids content 28.5 – 31.5% Total monomer content <100 ppm Arsenic  1 ppm Heavy metals max. 20 ppm Sulphated ash max. 0.1% Organic volatile conforms components

conforms conforms <100 mPas – 280 – 310 mg KOH per g of dry substance 43.2 – 47.6 – – conforms  95% <100 ppm  2 ppm max. 20 ppm  3.0% conforms

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Kollicoat® MAE grades

Solubility

Kollicoat® MAE 30 DP is freely miscible with water and retains its milky white appearance when mixed with it. A faintly opalescent, clear, viscous solution is obtained on mixing the product with acetone, ethanol or isopropyl alcohol in a ratio of 1 : 5. When an organic solvent is added to the product, the polymer initially precipitates, then redissolves as more is added.



Kollicoat® MAE 100P dissolves in methanol and ethanol to yield clear to slightly cloudy solutions.



The Kollicoat® MAE products are also soluble in dilute alkaline solutions.

Film formation

10 g of Kollicoat® MAE 30 DP is mixed with 0.3 g of triethyl citrate. 2 g of Kollicoat® MAE 100P is dispersed in 8 g of water to which 0.2 g triethyl citrate is added.



The mixture is poured onto a sheet of glass: a clear film forms as the water evaporates.

Viscosity

The viscosity of Kollicoat® MAE 30 DP is determined by the EN ISO 3219 method with a shear rate of 250 s-1 at 23°C. The viscosity of Kollicoat® MAE 100P in a 20% aqueous dispersion is determined at 23°C in a Brookfield viscometer (rotor 2, 100 rpm). The dispersion should be homogenized for 3 – 4 hours before it is measured.

Coagulate content

Filter 100 g of substance through a 90-µm screen. Dry the residue to constant weight in an oven at 105°C.

Microbiological status

The microbiological status is tested by the method described in Ph. Eur. III, 5.1.4, Category 2 + 3.



Unless otherwise stated, the methods of determination are taken from the 1997 European Pharmacopoeia.

2.3 Pharmacopoeia

Kollicoat® MAE 30 DP conforms to the requirements in USP monograph, “Methacrylic Acid Copolymer Type C”, JPE monograph; “Methacrylic Acid Copolymer LD” and Ph. Eur. monograph, “Methacrylic acid – Ethyl Acrylate Copolymer Dispersion 30%”. Kollicoat® MAE 100P contains carboxyl groups, some of which are neutralized. The dispersion from which it is produced meets the requirements of the USP, Ph. Eur. and JPE monographs.

3. Applications and typical formulations 3.1 Processing instructions

Plasticizers are essential to improve the flexibility of the films.



Suitable plasticizers or gloss intensifiers are • 1,2-propylene glycol • Triethyl citrate • Polyethylene glycols • Triacetin



The amount of plasticizer to add is 10 – 25% of the dry polymer. The Kollicoat® MAE grades are incompatible with magnesium stearate. However, any magnesium stearate in the product to be coated presents no problems. 1.2-propylene glycol improves the processability and barrier properties of the film coatings. A number of factors may cause aqueous dispersions to coagulate during processing, rendering them unusable: • the addition of finely divided pigments • high shear gradients on stirring and grinding • addition of emulsifying agents, stabilizers or wetting agents • changes in pH • cationic additives • organic solvents. • the formation of foam

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Kollicoat® MAE grades



Foam formation during processing can be prevented by adding a silicone antifoam such as Pharsil 21046.



Flat-plate stirrers have proved suitable for the production of spray suspensions.



Spray suspensions with a 15 – 30% solids content give good results and save time in spraying.



To avoid problems in incorporating auxiliaries in the aqueous suspensions, we recommend to:



• dilute the dispersion to a solids content of 20% • stir the desired auxiliary into the dispersion in the form of a dilute solution.



The following excipients can be included in a film-coating formulation:



• Talc • Syloid • Aerosil and • Kaolin as release and smoothing agents; • pigments



The Kollicoat® MAE grades have a high pigment binding capacity: two to three parts of pigments or other auxiliaries may be added for one part of solid polymer.

Redispersion of Kollicoat® MAE 100P

Stirring the powder into water yields an aqueous dispersion with technical and processing properties similar to those of the Kollicoat® MAE 30 DP dispersion on which it is based.



Procedure: Add the powder to the specified quantity of water with stirring. When adding the powder, ensure that • it does not form lumps, • it is immediately wetted, • the speed of the stirrer always matches the viscosity, • not too much foam forms.



To avoid lump formation and deposits on the stirrer, a stirrer with no horizontal surfaces, e. g. a bar or gate-type should be used.



When the powder has been incorporated, the viscosity rises and then falls again on further stirring. The dispersion should be stirred for 2 – 4 hours to ensure complete redispersion. It must be ensured that not too much air is entrained in the dispersion when it thickens.



A concentration of 20% has been found to be the optimum. The further steps in the preparation of a sprayable dispersion are essentially the same as for Kollicoat® MAE 30 DP.



It is not necessary to add any other auxiliaries such as alkali to redisperse Kollicoat® MAE 100P. The powder already contains the necessary proportion of neutralized methacrylic acid groups.

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3.2 Coloured enteric film  coatings for tablets Composition of the spray suspension

The formulation below is calculated for 5 kg of cores (diameter 9 mm; weight 330 mg) Parts by weight, g Polymer suspension

% composition

Alternative I Kollicoat® MAE 30 DP Propylene glycol Water

495.00 22.28 319.27

50.00 2.25 32.25

Alternative II Kollicoat® MAE 100P Propylene glycol Water

148.50 22.28 665.77

15.00 2.25 67.25

4.95 4.95 39.60 103.95 990.00

0.5 0.5 4.0 10.5 100.0

Pigment suspension Titanum dioxide Sicovit® Red 30 Talc Water

Solids content of the spray suspension Content of polymer dry substance Polymer applied (as solids) Total solids applied

22.25% 15.0% 4.0 mg/cm2 5.9 mg/cm2

Preparation of the spray suspension

Polymer suspension



Kollicoat® MAE 30 DP: Polypropylene glycol is first stirred into the specified amount of water. Kollicoat® MAE 30 DP is then stirred in.



Kollicoat® MAE 100P is dispersed in the specified amount of water. When it is completely dispersed, the plasticizer is incorporated.



Pigment suspension



Sicovit® Red 30, titanium dioxide and talc are intensively stirred into the specified amount of water and homogenized in a corundum disk mill.



Spray suspension



The pigment suspension is stirred into the coating suspension. The spray suspension must be stirred during spraying to prevent the solid substances settling out.

Machine parameters

Coating pan: Size of batch: Air supply temperature: Product temperature: Spraying pressure: Spraying rate: Spraying time:

Accela Cota 24” (Manesty) 5 kg 60°C 32 – 35°C 2 bar 40 g/m 25 – 30 min

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Release rates of diclofenac Na and acetylsalicylic acid tablets



The tablets were made with the following formulations:



a) Acetylsalicylic acid Acetylsalicylic acid 100 mg, Ludipress® 148,5 mg, Avicel® PH 102 50.0 mg, magnesium stearate 1.5 mg



b) Diclofenac Na Diclofenac Na 49.7 mg, Ludipress® 201.4 mg, Kollidon® VA 64 14.9 mg, Kollidon® CL 5.0 mg, Aerosil® 200 1.2 mg, magnesium stearate 2.8 mg



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3.3 Coloured enteric film coatings   for pellets and crystals Composition of the spray suspension

The formulation has been calculated for 500 g of crystals (diameter 0.3 –1.0 mm) Parts by weight, g Polymer suspension Alternative I Kollicoat® MAE 30 DP Propylene glycol Water Alternative II Kollicoat® MAE 100P Propylene glycol Water

Proportion, %

495.00 22.28 319.27

50.00 2.25 32.25

148.50 22.28 665.77 6

15.00 2.25 7.25

4.95 4.95 39.60 103.95 990.00

0.5 0.5 4.0 10.5 100,0

Pigment suspension Titanium dioxide Sicovit® Red 30 Talc Water

Solids content of the spray suspension Solid polymer in the spray suspension Solid polymer applied Total solids applied

Preparation of the spray suspension Machine parameters

4.0 mg/cm2 5.9 mg/cm2

See the processing notes under 3.2 Coating pan: Size of batch: Air supply temperature: Exhaust air temperature: Spraying pressure: Spraying time:

22.25% 15.0%

WSG Aeromatic Strea 1 500 g 60°C 35°C 1 bar 100 min

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Kollicoat® MAE grades

Release rates of diclofenac Na pellets and acetylsalicylic acid crystals



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3.4 White enteric film coatings   for pellets Composition of the spray suspension

The formulation below is calculated for 5 kg of pellets (diameter 0.8-1.2 mm) Parts by Weight, g Composition, % Polymer suspension Alternative I Kollicoat® MAE 30 DP Propylene glycol Water

2250.0 67.5 1435.0

50.0 1.5 31.9

Alternative II Kollicoat® MAE 100P Propylene glycol Water

675.0 67.5 3010.5

15.0 1.5 66.9

22.5 45.0 180.0 500.0 4500.0

0.5 1.0 4.0 11.1 100.0

Pigment suspension Kollidon® 30 Titanium dioxide Talc Water

Solids content of the spray suspension Dry polymer content Solid polymer applied Total solids applied

22.0% 15.0% 2.0 mg/cm2 2.9 mg/cm2

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Preparation of the spray suspension

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Kollicoat® MAE grades

Polymer suspension See the processing notes under 3.2. Pigment suspension Dissolve Kollidon 30 in the specified amount of water. Proceed as usual. Spray suspension See suggested method under 3.2.

Machine parameters

Coating pan: Size of batch: Air supply temperature: Exhaust air temperature: Spraying rate: Spraying time:

Hüttlin Kugelcoater HKC 5 TJ 5 kg 60°C 32 – 35°C 45 g/m 100 min

3.5 Colourless enteric coatings   for soft gelatin capsules Composition of the spray

The formulation below is intended for 5 kg of soft gelatin capsules Parts by weight, g Composition, % Polymer suspension Alternative I Kollicoat® MAE 30 DP Propylene glycol Water Alternative II Kollicoat® MAE 100P Propylene glycol Water

1680.0 100.8

70.0 4.2

619.2

25.8

504.0 100.8 1795.2

21.0 4.2 74.8 100.0

2400.0 Solids content of the spray suspension Content of polymer dry substance Polymer applied (as solids) Total solids applied

Preparation of the spray suspension

25.2% 21.0% 10.0m g/cm2 12.0 mg/cm2

Polymer suspension



Kollicoat® MAE 30 DP: polypropylene glycol is first dissolved in the specified amount of water. Then Kollicoat® MAE 30 DP is stirred in.



Kollicoat® MAE 100P is dispersed in the specified quantity of water. When it is completely dissolved, the plasticizer is added.

Machine parameters

Coating pan: Size of batch: Inlet air temperature: Product temperature: Spraying pressure: Spraying rate: Spraying time:

Accela Cota 24“ (Manesty) 5 kg 50°C 30 – 32°C 2 bar 30 – 35 g/m 70 min

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Kollicoat® MAE grades

3.6 Subcoating of tablet cores Some tablet cores contain a water-sensitive drug or a highly effective tablet disintegrant, e. g. Kollidon CL and must therefore be given a coating that provides a barrier to water before they can be coated with aqueous solutions. The same applies if the cores are too soft, or if an aqueous coating will not take to their surface. In such cases, heating the cores to about 35°C and spraying them with a 10% solution of Kollidon® VA 64, e. g. in isopropanol has given good results. Experience indicates that an adequate subcoating film is built up when small amounts of Kollidon® VA 64 are applied, i. e. approx. 0.4 mg/cm2.

3.7 Further applications

Fine coatings of 0.5 – 2.0 mg/cm2 (solids), can be applied for the following purposes:



• masking unpleasant tastes and odours, • as a barrier between incompatible active substances, • protection against atmospheric humidity.

3.8 Patents

EP 152 038 and EP 208 213 concerning aqueous dispersions for coating pharmaceutical products containing dispersed latex particles (A) of a polymer that contains carboxyl groups soluble in water between pH 5.0 and 8.0 and (B) a film-forming polymer (of great elasticity) that is insoluble in water, in which the weight ratio of the total amount of latex particles A and B lies between 60 : 40 and 5 : 95.

4. Storage

Kollicoat® MAE 30 DP should be protected from frost and kept below 30°C.

5. Shelf life

Kollicoat® MAE grades are stable for at least 18 months in the unopened original drums at room temperature. If aqueous dispersions are exposed to heat or frost, or if foam is formed, they may coagulate and become unusable. Once a drum has been opened, care must be taken to avoid introducing contamination, and the contents must be used up within a few weeks.

6. PBG Number

Kollicoat® MAE 30 DP Kollicoat® MAE 100P

7. Packaging

Kollicoat® MAE 30 DP: 25 l polyethylene drums. Also available in 1,000-l IBCs.

10 209 320 10 234 572

Kollicoat® MAE 100P: 20-kg with a PE inliner.

Note The data contained in this publication are based on our current knowledge and experience. In view of the many factors that may affect processing and application of our product, these data do not relieve processors from carrying out their own investigations and tests; neither do these data imply any guarantee of certain properties, nor the suitability of the product for a specific purpose. Any descriptions, drawings, photographs, data, proportions, weights etc. given herein may change without prior information and do not constitute the agreed contractual quality of the product. It is the responsibility of the recipient of our products to ensure that any proprietary rights and existing laws and legislation are observed. April 2006

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BASF Aktiengesellschaft Fine Chemicals Division - Pharma Solutions - 67117 Limburgerhof - www.pharma-solutions.basf.com

Kollicoat® MAE grades