Rapidly dispersible, fine-particle film-coating composition which is in powder form, is not prone to segregation and is based on polyvinyl alcohol-polyether graft copolymers characterized by particular physical stability and low asperity

Abstract

A rapidly dispersible, fine-particle film-coating composition which is in powder form and is not prone to segregation for coating pharmaceutical dosage forms, consisting of a) 40-90% by weight of a polyvinyl alcohol-polyether graft copolymer (component A), b) 1-20% by weight of a polyvinylpyrrolidone or of a vinylpyrrolidone-vinyl acetate-copolymer with a K value of from 10 to 100 (component B) c) 10-60% by weight of organic or inorganic pigments having an average particle size of less than 8 μm (component C) d) 0.5-15% by weight of a surfactant having an HLB of greater than 10 (component D) and e) 0-30% by weight of further customary coating ingredients (components E),
in which the particles of component C are embedded in a coherent polymer matrix,
where the total amount of components A to E is 100% by weight.

Claims

1. A rapidly dispersible, fine-particle film-coating composition which is in powder form and is not prone to segregation for coating pharmaceutical dosage forms, comprising: a) 40-90% by weight of a polyvinyl alcohol-polyether graft copolymer (component A), b) 1-20% by weight of a polyvinylpyrrolidone or of a vinylpyrrolidone-vinyl acetate-copolymer with a K value of from 10 to 100 (component B) c) 10-60% by weight of organic or inorganic pigment particles having an average pigment particle size of less than 8 μm (component C) d) 0.5-15% by weight of a surfactant having an HLB of greater than 10 (component D) and e) 0-30% by weight of additional coating ingredients (components E), in which the pigment particles of component C are completely surrounded by water soluble polymer, where the total amount of components A to E is 100% by weight.

2. The film-coating composition according to claim 1, wherein component B has a K value between 12 and 60.

3. The film-coating composition according to claim 1, wherein component B has a K value between 20 and 50.

4. The film-coating composition according to claim 1, wherein component B is a polyvinylpyrrolidone with a K value between 25 and 35 or a vinylpyrrolidone-vinyl acetate copolymer in the ratio 6:4 with a K value between 20 and 40.

5. The film-coating composition according to claim 1, wherein component C has the average pigment particle size of less than 6 μm.

6. The film-coating composition according to claim 1, wherein component C has the average pigment particle size of less than 4 μm.

7. The film-coating composition according to claim 1, wherein component C is selected from the group consisting of aluminum silicates, magnesium silicates, magnesium aluminum silicates, iron oxide, titanium dioxide, zinc oxide, silica, organic lakes and mixtures thereof.

8. The film-coating composition according to claim 1, wherein component C is selected from the group consisting of talc, kaolin, titanium dioxide, iron oxide and mixtures thereof.

9. The film-coating composition according to claim 1, wherein component D is at least one selected from the group consisting of alkali metal salts of fatty acids, alkylsulfonates, alkyl sulfates or alkylarylsulfonates, ethoxylates of fatty acids, fatty alcohols, fatty acid glycerides, sorbitan fatty acid esters, sorbitan fatty alcohol ethers, phenols and polyoxypropylene-polyoxyethylene block copolymers.

10. The film-coating composition according to claim 1, wherein sodium lauryl sulfate is employed as component D.

11. The film-coating composition according to claim 1, wherein component A is present in a concentration of 50-80% by weight.

12. The film-coating composition according to claim 1, wherein component B is present in a concentration of 2-15% by weight.

13. The film-coating composition according to claim 1, wherein component B is present in a concentration of 5-10% by weight.

14. The film-coating composition according to any claim 1, wherein component C is present in a concentration of 15-50% by weight.

15. The film-coating composition according to claim 1, wherein component C is present in a concentration of 20-45% by weight.

16. The film-coating composition according to claim 1, wherein talc or kaolin in a concentration of 5-30% by weight and titanium dioxide in a concentration of 10-40% by weight are employed as component C.

17. The film-coating composition according to claim 1, wherein component D is present in a concentration of 0.5-10% by weight.

18. The film-coating composition according to claim 1, wherein component D is present in a concentration of 1-5% by weight.

19. The film-coating composition according to claim 1, comprising a) 60-65% by weight of a polyvinyl alcohol-polyether graft copolymer (component A), b) 5-10% by weight of a vinylpyrrolidone-vinyl acetate copolymer (component B) c) 14-18% by weight of talc or kaolin having the average pigment particle size of less than 8 μm, and 12-16% by weight of titanium dioxide having the average pigment particle size of less than 8 μm (component C) and d) 1-3% by weight of sodium lauryl sulfate (component D).

20. The film-coating composition according to claim 1, wherein water-soluble colorants, non-stick agents, fillers, gloss improvers, antifoams, protective colloids, buffer substances, pH-regulating substances, bonding agents or plasticizers are employed as components E.

21. The film-coating composition according to claim 1, wherein the individual components are intimately associated with one another and cannot be separated by sieving or sifting.

22. The film-coating composition according to claim 1, wherein the average particle size of the pigment particle is less than 8 μm after redispersion in water by stirring.

23. The film-coating composition according to claim 1, wherein the average particle size of the pigment particle is less than 6 μm after redispersion in water by stirring.

24. The film-coating composition according to claim 1, wherein the average particle size of the pigment particle is less than 4 μm after redispersion in water by stirring.

25. The film-coating composition according to claim 1, wherein the average particle size of the powder is greater than 50 μm.

26. The film-coating composition according to claim 1, wherein the average particle size of the powder is greater than 100 μm.

27. The film-coating composition according to claim 1, wherein the average particle size of the powder is greater than 150 μm.

28. A process for producing a film-coating composition according to claim 1, which comprises grinding component C in water to the required particle size, combining with the other components and, optionally additional water, and drying the resulting aqueous dispersion.

29. A process for producing a film-coating composition according to claim 1, which comprises grinding component C in water in the presence of component A, component B, component D or component E or combinations thereof to the required particle size, combining with the remaining components and, optionally additional water, and drying the resulting aqueous dispersion.

30. A process for producing a film-coating composition according to claim 1, which comprises grinding component C in water in the presence of components B and D and, optionally, E to the required particle size, combining with an aqueous solution of component A and, optionally additional water, and drying the resulting aqueous dispersion.

31. A process for producing a film-coating composition according to claim 1, wherein component C is ground in water in the presence of complete quantities or partial quantities of components A, B, D or E or combinations thereof to the required particle size, drying to a powder or granules, and mixing with the remaining quantities of component A, B, D and E in powder form.

32. A process for producing a film-coating composition according to claim 1, which comprises grinding component C in water in the presence of components B, D or E or combinations thereof to the required particle size, drying the resulting aqueous dispersion and mixing with component A in powder form.

33. The process according to claim 28, wherein the drying of the aqueous dispersion takes place by spray drying, fluidized bed drying, drum drying or spray granulation.

34. The process according to claim 33, wherein the spray drying takes place at inlet air temperatures of 60-200° C.

35. The process according to claim 34, wherein the atomization of the suspension in the spray drying takes place at pressures greater than 0.1 MPa.

36. The process according to claim 28, wherein the product obtained in powder form after drying of the aqueous dispersion is mixed with further coloring components in powder form and, optionally, compacted, extruded, pelleted or granulated.

37. The process according to claim 28, wherein a film-coating composition which is in powder form and comprises only white pigments is mixed with coloring components in powder form and, optionally, compacted, extruded, pelleted or granulated.

38. A process for producing coated pharmaceutical dosage forms, which comprises stirring a film-coating composition according to claim 1 into water, mixing with additional components and applying to a substrate by means of a suitable spraying device, with successive drying of the film coating by feeding in heated air.

39. A solid pharmaceutical dosage form coated with the film-coating composition according to claim 1.

40. A solid pharmaceutical dosage form according to claim 39, which comprises as active ingredients medicinal substances, vitamins, carotenoids, minerals, dietary supplements or trace elements.

41. A solid pharmaceutical dosage form according to claim 39, wherein tablets, extrudates or capsules are provided with a film coating.

42. A rapidly dispersible, fine-particle film-coating composition which is in powder form and is not prone to segregation for coating pharmaceutical dosage forms, comprising: a) 40-90% by weight of a polyvinyl alcohol-polyether graft copolymer (component A), b) 1-20% by weight of a polyvinylpyrrolidone or of a vinylpyrrolidone-vinyl acetate-copolymer with a K value of from 10 to 100 (component B) c) 10-60% by weight of organic or inorganic pigment particles having an average pigment particle size of less than 8 μm (component C) d) 0.5-15% by weight of a surfactant having an HLB of greater than 10 (component D) and f) 0-30% by weight of additional coating ingredients (components E), in which the pigment particles of component C are completely surrounded by water-soluble polymer, where the total amount of components A to E is 100% by weight; wherein the composition is made in a process consisting of: A) grinding component C in water to the required particle size, combining with the other components and, optionally additional water, and drying the resulting aqueous dispersion, or B) grinding component C in water in the presence of component A, component B, component D or component E or combinations thereof to the required particle size, combining with the remaining components and, optionally additional water, and drying the resulting aqueous dispersion, or C) grinding component C in water in the presence of components B and D and, optionally, E to the required particle size, combining with an aqueous solution of component A and, optionally additional water, and drying the resulting aqueous dispersion, or D) grinding component C in water in the presence of complete quantities or partial quantities of components A, B, D or E or combinations thereof to the required particle size, drying to a powder or granules, and mixing with the remaining quantities of component A, B, D and E in powder form, or E) grinding component C in water in the presence of components B, D or E or combinations thereof to the required particle size, drying the resulting aqueous dispersion and mixing with component A in powder form.

43. A rapidly dispersible, fine-particle film-coating composition which is in powder form and is not prone to segregation for coating pharmaceutical dosage forms, consisting of: a) 40-90% by weight of a polyvinyl alcohol-polyether graft copolymer (component A), b) 1-20% by weight of a polyvinylpyrrolidone or of a vinylpyrrolidone-vinyl acetate-copolymer with a K value of from 10 to 100 (component B) c) 10-60% by weight of organic or inorganic pigment particles having an average pigment particle size of less than 8 μm (component C) d) 0.5-15% by weight of a surfactant having an HLB of greater than 10 (component D) and g) 0-30% by weight of additional coating ingredients (components E) selected from the group consisting of water-soluble colorants, non-stick agents, fillers, gloss improvers, antifoams, protective colloids, buffer substances, pH-regulating substances, bonding agents, and combinations thereof, in which the pigment particles of component C are completely surrounded by water-soluble polymer.

Description

EXAMPLES

(1) The percentage data relate, unless indicated otherwise, to % by weight.

(2) The statements about particle sizes relate to average particle sizes. The particle sizes were determined by laser diffraction, using the D[4,3] value for the analysis.

(3) The resistance to crushing was determined in a Krämer automatic tablet tester.

(4) The friability was determined in an Erweka Friabilator for 4 min at 25 rpm.

(5) The disintegration time was determined as specified in the European Pharmacopoeia. The release was likewise determined as specified in the European Pharmacopoeia.

Example 1

(6) Composition of the Film Coating:

(7) TABLE-US-00001 Polyvinyl alcohol-polyethylene glycol 6000 (75:25) 60% graft copolymer (degree of hydrolysis 94 mol %) Vinylpyrrolidone-vinyl acetate 6:4 copolymer 10% (copolyvidone) Talc 20% Titanium dioxide  9% Sodium lauryl sulfate  1%
Production:

(8) All the ingredients were stirred into water, using a paddle stirrer, in direct succession in the sequence listed above to result in a solids concentration of 25%. This dispersion was ground using a Skandex ball mill with 0.6-1.25 mm milling elements to an average particle size of the pigment particles of 3.5 μm and then spray dried with an inlet air temperature of 130° C. to result in a free-flowing powder with a particle size of 105 μm.

(9) Use

(10) 150.0 g of the preparation were stirred by means of a paddle stirrer into 450.0 g of water. The dissolution or dispersion was complete after 8 min. The spray suspension was of low viscosity and homogeneous. The particle size of the pigment particles after redispersion was 3.1 μm.

(11) The spray suspension was sprayed in a horizontal drum coater (24″ Accela-Cota) onto 5 kg of furosemide tablets of the following composition:

(12) TABLE-US-00002 Furosemide 40 mg Ludipress ® (BASF AG) .sup.1) 97.5 mg Copolyvidone 12.5 mg Microcrystalline cellulose .sup.2) 97.5 mg Magnesium stearate 2.5 mg Total weight 250 mg Diameter: 9 mm, biconvex .sup.1) Formulated product of 93% by weight lactose, 3.5% by weight povidone K30 and 3.5% by weight crospovidone .sup.2) Average particle size 100 μm
Spraying Conditions:

(13) TABLE-US-00003 Inlet air temperature 65° C. Outlet air temperature 33° C. Spraying rate 50 g/min Spraying pressure 0.4 MPa Amount applied 600 g of spray dispersion, equivalent to 150 g of solid Spraying time 12 min
Film-Coated Tablet Properties:

(14) TABLE-US-00004 Resistance to crushing 105N Friability 0% Disintegration time 3:25 (min:s) Release 20 min: 100%

(15) The coating was smooth, uniform and homogeneous. The imprint was nicely reproduced without blurring effects or bridge formation. No prolongation of the disintegration time or of active ingredient release compared with the uncoated tablet core was to be found. The resistance to crushing was 21 N higher than for the uncoated core. No changes in the properties of the film-coated tablets were found during a stability test lasting 12 months.

Example 2

(16) Composition of the Film Coating:

(17) TABLE-US-00005 Polyvinyl alcohol-polyethylene glycol 6000 (75:25) 61% graft copolymer (degree of hydrolysis 94 mol %) Vinylpyrrolidone-vinyl acetate 6:4 copolymer  7% (copolyvidone) Kaolin 16% Titanium dioxide 14% Sodium lauryl sulfate  2%
Production:

(18) 0.7 kg of copolyvidone were dissolved in 6.3 kg of water and then 1.6 kg of kaolin and 1.4 kg of titanium dioxide were introduced. This coarse dispersion was ground in a Coruma-type rotor-stator dispersing unit for 3 h to result in an average particle size of 2.0 μm. This pigment suspension was introduced into a stirred solution of 6.1 kg of polyvinyl alcohol-polyethylene glycol graft copolymer and 0.2 kg of sodium lauryl sulfate in 17.3 kg of water. Spray drying took place at an inlet air temperature of 140° C., with the fines being removed from the spray-dried powder and blown in again in front of the spray nozzle to result in agglomeration and a coarser particle size (agglomerating spray drying or FSD technology). The film-coating compositions were obtained as free-flowing powders with particle sizes of 210 μm.

(19) Use

(20) This preparation was stirred using a paddle stirrer into water to result in a spray preparation with a solids content of 30%. Dissolution or dispersion was complete after 6 min. The spray suspension was of low viscosity and homogeneous. The particle size of the pigment particles after redispersion was 1.7 μm.

(21) The spray suspension was sprayed in a horizontal drum coater (24″ Accela-Cota) onto 5 kg of Ambroxol HCl tablets:

(22) Spraying Conditions:

(23) TABLE-US-00006 Inlet air temperature 75° C. Outlet air temperature 37° C. Spraying rate 60 g/min Spraying pressure 0.4 MPa Amount applied 600 g of spray dispersion, equivalent to 180 g of solid Spraying time 10 min
Film-Coated Tablet Properties:

(24) TABLE-US-00007 Resistance to crushing 107N Friability 0% Disintegration time 2:23 (min:s) Release 20 min: 100%

(25) The coating was smooth, uniform and homogeneous. The imprint was nicely reproduced without blurring effects or bridge formation. No prolongation of the disintegration time or of active ingredient release compared with the core was to be found. The resistance to crushing was 25 N higher than for the core. No changes in the properties of the film-coated tablets were found during a stability test lasting 12 months.

Example 3

(26) Composition of the Film Coating:

(27) TABLE-US-00008 Polyvinyl alcohol-polyethylene glycol 6000 (75:25) 40% graft copolymer (degree of hydrolysis 94 mol %) Polyvinylpyrrolidone of K value 30 18% Kaolin 30% Titanium dioxide 10.5% Cremophor ® RH 40 .sup.1) 1.5% Ethoxylated hydrogenated castor oil with 40 EO units
Production:

(28) 1.8 kg of polyvinylpyrrolidone of K value 30 were dissolved in 8.0 kg of water and then 3.0 kg of kaolin and 1.05 kg of titanium dioxide were introduced. This coarse dispersion was ground in a ball mill with milling elements of 0.8-1.25 mm for 2.5 h to result in an average particle size of 2.5 μm. This pigment suspension was introduced into a stirred solution of 4.0 kg of polyvinyl alcohol-polyethylene glycol graft copolymer and 0.15 kg of Cremophor RH 40 in 22.0 kg of water. Drying took place in a fluidized bed dryer at an inlet air temperature of 90° C. Free-flowing powders with particle sizes of 315 μm were obtained.

(29) Use

(30) The spray suspension was produced by stirring the preparation by means of a paddle stirrer into water to result in a spray preparation with a solids content of 30%.

(31) Dissolution or dispersion was complete after 7 min. The spray suspension was of low viscosity and homogeneous. The particle size of the pigment particles after redispersion was 2.3 μm.

(32) The spray suspension was sprayed in a horizontal drum coater (24″ Accela-Cota) onto 5 kg of caffeine tablets of the following composition:

(33) TABLE-US-00009 Caffeine 50 mg Ludipress (BASF AG) 229 mg Microcrystalline cellulose .sup.1) 40 mg Crospovidone 10 mg Magnesium stearate 1 mg Total weight 330 mg Diameter: 9 mm, biconvex .sup.1) Average particle size 100 μm
Spraying Conditions:

(34) TABLE-US-00010 Inlet air temperature 70° C. Outlet air temperature 41° C. Spraying rate 48 g/min Spraying pressure 0.45 MPa Amount applied 600 g of spray dispersion equivalent to 180 g of solid Spraying time 12.5 min
Film-Coated Tablet Properties:

(35) TABLE-US-00011 Resistance to crushing 131N Friability 0% Disintegration time 2:48 (min:s) Release 20 min: 100%

(36) The coating was smooth, uniform and homogeneous. The imprint was nicely reproduced without blurring effects or bridge formation. No prolongation of the disintegration time or of active ingredient release compared with the core was to be found. The resistance to crushing was 26 N higher than for the core. No changes in the properties of the film-coated tablets were found during a stability test lasting 12 months.

Example 4

(37) Composition of the Film Coating

(38) TABLE-US-00012 Polyvinyl alcohol-polyethylene glycol 6000 (75:25) 53.5% graft copolymer (degree of hydrolysis 94 mol %) Vinylpyrrolidone-vinyl acetate 6:4 copolymer 7.5% (copolyvidone) Sodium dihydrogen phosphate 1% Titanium dioxide 35% Poloxamer 188 (Lutrol F 68) 1.25% Polydimethylsiloxane (simethicone) 0.25% Quinoline yellow lake 1.5%
Production:

(39) All the ingredients were stirred into water, using a straight-arm stirrer, in direct succession in the sequence determined above to result in a solids concentration of 30%. This dispersion was ground using a Coruma-type rotor-stator dispersing unit for 2 h to an average particle size of 1.5 μm and then spray dried at an inlet air temperature of 120° C. to result in a free-flowing powder with particle sizes of 110 μm.

(40) Use

(41) 160.0 g of the preparation were stirred by means of a paddle stirrer into 480.0 g of water. Dissolution or dispersion was complete after 5 min. The spray suspension was of low viscosity and homogeneous. The particle size of the pigment particles after redispersion was 1.3 μm.

(42) The spray-suspension was sprayed in a horizontal drum coater (24″ Accela-Cota) onto 5 kg of propranolo HCl tablets of the following composition:

(43) TABLE-US-00013 Propranolol HCl 50 mg Ludipress (BASF AG) .sup.1) 97.5 mg Copolyvidone 12.5 mg Microcrystalline cellulose .sup.2) 97.5 mg Magnesium stearate 2.5 mg Total weight 260 mg Diameter: 9 mm, biconvex .sup.1) Formulated product of 93% by weight lactose, 3.5% by weight povidone and 3.5% by weight crospovidone .sup.2) Average particle size 100 μm
Spraying Conditions:

(44) TABLE-US-00014 Inlet air temperature 65° C. Outlet air temperature 35° C. Spraying rate 45 g/min Spraying pressure 0.4 MPa Amount applied 640 g of spray dispersion, equivalent to 160 g of solid Spraying time 14 min
Film-Coated Tablet Properties:

(45) TABLE-US-00015 Resistance to crushing 110N Friability 0% Disintegration time 3:15 (min:s) Release 20 min: 100%

(46) The coating was smooth, uniform and homogeneous. The imprint was nicely reproduced without blurring effects or bridge formation. No prolongation of the disintegration time or of active ingredient release compared with the core was to be found. The resistance to crushing was 26 N higher than for the core. No changes in the properties of the film-coated tablets were found during a stability test lasting 12 months.

Example 5

(47) 10.0 kg of the white preparation from example 1 were mixed with 0.5 kg of very finely ground red iron oxide in a ploughshare mixer for 15 min and compacted in a Gerteis roller compactor under a force of 3 kN and with a slit width of 3 mm, and the resulting compact was passed through a sieve with a mesh width of 1.0 mm. The preparation produced in this way dispersed in water within 8 min to give a fine stable dispersion. The latter was sprayed onto tablets in analogy to example 1.

(48) The coating was smooth, uniform and homogeneous. The imprint was nicely reproduced without blurring effects or bridge formation. No prolongation of the disintegration time or of active ingredient release compared with the core was to be found.

Example 6

(49) 150 g of the white preparation from example 2 were dispersed in 470 g of water with stirring. Immediately thereafter, a liquid color premix consisting of 6 g of indigotine lake, 1 g of poloxamer 188 and 10 g of water was stirred into this dispersion. After stirring for 10 min, the preparation was ready for spraying and was sprayed onto tablets in analogy to example 2.

(50) The coating was smooth, uniform and homogeneous. The imprint was nicely reproduced without blurring effects or bridge formation. No prolongation of the disintegration time or of active ingredient release compared with the core was to be found. No changes in the properties of the film-coated tablets were found during a stability test lasting 12 months.