Kollicoat IR. Technical Information

Transcription

1 Technical Information Kollicoat IR February 2013 Supersedes issue dated February _030724e-11/Page 1 of 14 WF-No.: = Registered trademark of BASF Polyvinyl alcohol-polyethylene glycol graft copolymer for instant-release coatings and quick-dissolving formulations

2 03_030724e-11 February 2013 Page 2 of 14 Kollicoat IR Contents Page 1. Introduction General Structural formula Physical form 3 2. Specification and properties Chemical nature Physicochemical properties Specification Regulatory status Properties of aqueous solutions Film properties 5 3. Application and processing Applications Processing notes 6 4. Typical formulations Instant release coating Propranolol film-coated tablets Instant release coating Caffeine tablets Wet binding Acetaminophen instant granules Drug layering Layering of Riboflavin onto pellets Pore former in sustained release coating Propranolol single unit drug delivery system Wet binding Using GranuLac Storage conditions Stability Toxicology PRD-No Packaging 14

3 03_030724e-11 February 2013 Page 3 of 14 Kollicoat IR 1. Introduction 1.1 General Kollicoat IR is a polyvinyl alcohol-polyethylene glycol graft copolymer that is freely soluble in water. It is used mainly for the production of instant-release coatings for tablets. 1.2 Structural formula O H HO n n-x O X OH OH m 1.3 Physical form Kollicoat IR is a white to faintly yellow free-flowing powder. 2. Specification and properties 2.1 Chemical nature The polymer consists of 75% polyvinyl alcohol units and 25% polyethylene glycol units. The product also contains approx. 0.3% colloidal silica to improve its flow properties. 2.2 Physicochemical properties As a result of its structure, the polymer dissolves very readily in acidic, neutral and alkaline aqueous media. Such aqueous solutions have a comparatively low viscosity. Molecular weight Approx Daltons Solubility Solutions of Kollicoat IR with concentrations of up to 40% can be prepared in water and aqueous systems, e.g. weak acids or alkalis. Solutions of up to 25% can be prepared in a 1:1 ethanol-water mixture. Due to colloidal silica, aqueous solutions of Kollicoat IR are slightly turbid. Its solubility in non-polar solvents is low, and it can only be dispersed in these. Film formation An aqueous solution of Kollicoat IR is cast on a smooth surface. When the water has evaporated, a clear colourless flexible film remains (see 2.4, Film properties). 2.3 Specification See separate document: Standard Specification (not for regulatory purposes) available via BASF s WorldAccount: (registered access). Analytical procedures (non compendial methods) are supplied upon request.

4 03_030724e-11 February 2013 Page 4 of 14 Kollicoat IR 2.4 Regulatory status Kollicoat IR is registered around the world in medicinal products in all relevant regions, including Europe, Japan and the USA. Comprehensive safety documentation is available, including non-clinical studies. Kollicoat IR has received self-affirmed GRAS status as of January This status allows its formulation into products for the US dietary supplements market. Monographs & Registrations Ph.Eur. Macrogol poly(vinyl alcohol) graft polymer USP/NF PMDA (Japan) JPE IIG listing Ethylene glycol and vinyl alcohol graft copolymer Approved Listed FDA approval received Jan 2012, database listing expected 2.5 Properties of aqueous solutions Viscosity Though the viscosity of aqueous solutions of Kollicoat IR increases with the polymer concentration, yet at a much lower level than that of equivalent solutions, for instance, cellulose derivatives. 1.OE+04 Log. dynamic viscosity [mpas] 1.OE+03 1.OE+02 1.OE+01 1.OE Polymer concentration in water [%] Kollicoat IR Kollicoat Protect PVA HPMC 3 mpas HPMC 6 mpas Viscosity of aqueous Kollicoat IR solutions as a function of polymer concentration Surface activity Kollicoat IR reduces the surface tension of water. This makes aqueous solutions easy to spray, and the spray droplets exhibit good wetting behavior on the tablet surface.

5 03_030724e-11 February 2013 Page 5 of 14 Kollicoat IR 2.6 Film properties Kollicoat IR forms clear colour less films that are enor mously flex ible and dis solve very rap idly in water. Kollicoat IR films are not tacky, have a high pig ment bind ing capac ity and can read ily be printed. The reduction of the surface tension is specifically important for the processing in drug layering. Kollicoat IR has a much higher elon ga tion at break value than cel lu lose deriv a tives Strain [N/mm 2 ] Elongation [%] Kollicoat IR Kollicoat Protect PVA HPMC 3 mpas HPMC 6 mpas Elongation at break of various instant release polymers (54% r. h.)

6 03_030724e-11 February 2013 Page 6 of 14 Kollicoat IR 3. Application and processing 3.1 Applications Kollicoat IR can be used for all applications for which a water-soluble flexible polymer is required. Instant release coating Wet binder Pore former in sustained-release coatings Film former in sprays and transdermal therapeutic systems Suspension and emulsion stabiliser Protective colloid Film former in oral wafers The special advantages of Kollicoat IR lie in its enormous flexibility, low viscosity and rapid rate of dissolution. Kollicoat IR solutions for spraying onto tablets can be applied with a high solids content, which greatly reduces the coating time and minimizes costs. 3.2 Processing notes Because of the high elasticity of Kollicoat IR films, it is not nec es sary to add a plasticizer. A spray sus pen sion is best pre pared as fol lows: Dis solve Kollicoat IR in water and stir in the pre vi ously homo gen ized pig ment sus pen sion. The other water-sol u ble ingre dients can be dis solved together with the Kollicoat IR. The type and speed of the stir rer should be set such that lit tle or no foam is produced. As spray sus pen sions of Kollicoat IR have a lower vis cos ity than those of other instant release poly mers, they can have a much higher con cen tra tion. This greatly short ens the spray ing and pro cess ing time in the man u fac ture of film- coated tab lets. Poly mer con cen tra tions of 15 25% can be used, giv ing a total sol ids con cen tra tion of 20 35%, depend ing on the quan tity of pig ments. Since Kollicoat IR has sur fac tant prop er ties and can act as a pro tec tive col loid, it pre vents the aggre ga tion of the pig ment par ti cles and ensures that the pig ment is evenly dis trib uted over the tab let core. The great elas tic ity of Kollicoat IR ensures that it does not crack on the tab lets when they are exposed to dif fer ent humid ity con di tions in stor age, even when the cores con tain high amounts of disintegrant or pow er ful swell ing agents such as HPMC, xan than or algi nate which are fre quently used in sus tained release tab lets. The coat ing can be applied in all the usual coat ers, e.g. side-vented drum coat ers, fluid ised bed coat ers, solid wall coat ers, and coat ing pans under the usual con ditions for aque ous solu tions. The following conditions have been used successfully in numerous trials: Inlet air temperature: C Outlet air temperature: C Atomizing pressure: bar The product can very easily be cleaned off equipment with warm or cold water.

7 03_030724e-11 February 2013 Page 7 of 14 Kollicoat IR 4. Typical formulations 4.1 Instant release coating Propranolol film-coated tablets Composition of the tablets 40 mg propranolol HCl; 97.5 mg Ludipress ; 12.5 mg Kollidon VA 64; 97.5 mg MCC PH 102; 2.5 mg magnesium stearate Composition of the spray suspension The formulation is designed for 250 kg of tablets (tablet weight 250 mg; diameter 9 mm) Weight [g] Proportion [%] Polymer solution Kollicoat IR Water Pigment suspension Talc Titanium dioxide Iron Oxide Red Water Preparation of the spray suspension Polymer solution: Stir the Kollicoat IR into the specified quantity of water until it has dissolved. Pigment suspension: Vigorously stir talc, Iron Oxide Red and titanium dioxide into the specified quantity of water and homogenize in a high-shear mixer. Spray suspension: Stir the pig ment sus pen sion into the poly mer solu tion. To avoid sed i men ta tion dur ing the spray ing pro cess, the mix ture must be con tin u ously stirred.

8 03_030724e-11 February 2013 Page 8 of 14 Kollicoat IR Additional gloss coating If a certain appearance of the tablet is needed 5 wt% polyethylene glycol 6000 and Kollidon 17 (at a ratio of 9:1) should be dissolved in water and sprayed after the spray suspension. The achieved weight gain should be between mg/cm 2. Machine parameters Coating machine Driacoater type 900, perforated drum coater Batch size 250 kg Inlet air temperature 70 C Outlet air temperature 48 C Product temperature 50 C Air flow 4400 m 3 /h Atomizing pressure 6 bar Number of spray nozzles 6 Spraying rate 700 g/min Spraying time 55 min Final drying 60 C/5 min Quantity applied 3.8% Tablet properties Core Film-coated tablet Appearance White Red Hardness 93 N 109 N Friability 0% 0% Disintegration time 5: 53 [min: s] 5: 47 [min: s] Drug release 10 min: 49% 20 min: 98% 10 min: 54% 20 min: 99% 4.2 Instant release coating Caffeine tablets Composition of the tablets 50 mg caffeine; 229 mg Ludipress ; 10 mg Kollidon CL; 40 mg MCC PH 101; 1 mg magnesium stearate Composition of the spray solution The formulation is designed for 5 kg of tablets (weight 330 mg; diameter 9 mm) Proportion [%] Polymer solution Kollicoat IR Water Pigment suspension Talc Titanium dioxide Water

9 03_030724e-11 February 2013 Page 9 of 14 Kollicoat IR Preparation of the spray suspension Polymer solution: Stir the Kollicoat IR into the specified quantity of water until it has dissolved. Pigment suspension: Vigorously stir talc and titanium dioxide into the specified quantity of water and homogenize in a high-shear mixer. Spray suspension: Stir the pigment suspension into the polymer solution. To avoid sedimentation during the spraying process, the mixture must be continuously stirred. Additional gloss coating If a certain appearance of the tablet is needed 5 wt% polyethylene glycol 6000 and Kollidon 17 (at a ratio of 9:1) should be dissolved in water and sprayed after the spray suspension. The achieved weight gain should be between mg/cm 2. Machine parameters Coater Accela-Cota 24, perforated drum coater Batch size 5 kg Inlet air temperature 60 C Outlet air temperature 39 C Product temperature 35 C Air flow 180 m 3 /h Atomizing pressure 3 bar Number of spray nozzles 1 Spraying rate 30 g/min Spraying time 18 min Final drying 60 C/4 min Quantity applied 3 mg/cm 2 polymer Tablet properties Core Film-coated tablet Appearance White White Hardness 116 N 119 N Friability 0% 0% Disintegration time 0:58 [min:s] 0:51 [min:s] Drug release 10 min: 93% 20 min: 92% 10 min: 92% 20 min: 98%

10 03_030724e-11 February 2013 Page 10 of 14 Kollicoat IR 4.3 Wet binding Acetaminophen instant granules Composition of the powder mixture 49% acetaminophen, fine powder; 49% sorbitol; 2% aspartame; 0.06% aroma Composition of the binder solution The formulation is designed for 1 kg of powder mixture Weight [g] Proportion [%] Granulation solution Kollicoat IR Water Preparation of the binder solution Manufacture of the granules Stir the Kollicoat IR into the specified quantity of water until it has dissolved. Mix the components of the powder mixture for 10 min (Stephan mixer Type UMC 5 Electronic). Apply the Kollicoat IR solution in a fine spray, keeping the mixture in motion. Force the moist mass first through a 3 mm sieve, then a 1 mm sieve. Dry the moist granules and force them through a 1 mm sieve. Properties of the granules The granules dissolve in water within 1 min. 4.4 Drug layering Layering of Riboflavin onto pellets The pellets consists of sucrose & microcrystalline cellulose. Pellets size were mesh. Coating formulation for the tracer excipient Due to surface effects of Riboflavin, the tracer formulation had to be applied with a solid matter concentration of only 15%. Weight [g] Proportion [%] Granulation solution Riboflavin 10.0 Kollicoat IR 5.0 Water Coating formulation for the functional coat (taste masking) Weight [g] Proportion [%] Polymer solution Kollicoat Smartseal 30 D 50.5 ATBC (Acetyltributyl citrate) BHT (Butylated hydroxytoluene) DS (docusate sodium) 7.6 (15% based on pol.) 1.3 (2.5% based on pol.) 1.0 (2.0% based on pol.) Talc 39.0 FD & C Blue No (Brilliant Blue) 100.0

11 03_030724e-11 February 2013 Page 11 of 14 Kollicoat IR Equipments & process details Two different coating technologies were used 1. Side vented pan coater (SCP) Perfima Lab with slot drum. 2. Fluid bed coater (FBP) Ghibli Lab, with bottom spray configuration. Coating Pan FBP Batch size 25/30 kg/l kg/l Drum speed 18 rpm Inlet air temperature C C Inlet air quantity 600 m 3 /h Bore diameter nozzle 1.2 mm 1.2 mm Spray rate ml/min 25 ml/min Atomising pressure 1 bar 1.6 bar High drug load could be achieved due to high film elasticity of Kollicoat IR. 4.5 Pore former in sustained release coating Propranolol single unit drug delivery system Composition of the tablet Propanolol HCl (granulated) Weight [g] Proportion [%] Ludipress Kollidon VA Kollidon CL Aerosil Magnesium stearate Total Coating parameters Parameters Values Pan 24 Accela-Cota Batch size 5 kg Inlet air temperature 60 C Outlet air volume 216 m 3 /h Spray rate 30 gm/min Drying time 5 mins. Result Dissolution profile Propranolol drug delivery systems dissolution graph Dissolution [%] Kollicoat SR 30 D (KSR) + Kollicoat IR (KIR) = drug delivery system CORE KSR/KIR 5:5 KSR/KIR 6:4 KSR/KIR 7:3 KSR/KIR 8: time [h] Kollicoat IR acts as a very effective pore former in conjunction with a functional polymer to control the drug release.

12 03_030724e-11 February 2013 Page 12 of 14 Kollicoat IR 4.6 Wet binding Using GranuLac 200 Composition of the powder mixture 95% GranuLac 200 & 5% binder (Kollidon 25, Kollidon 90 & Kollicoat IR) Composition The formulation is designed for 1150 g of powder mixture Material Weight [g] Proportion [%] Kollicoat IR/Kollidon 30/ Kollidon 90 GranuLac The binder conc. in the aqueous solution ranges from %. Preparation of the binder solution Stir the Kollicoat IR into the specified quantity of water until it has dissolved. Parameter settings To get started with Kollicoat IR as a binder Parameters Binder content in the final granules Binder content in the polymer solution Process time Fluid bed granulation % 5% is to be preferred for obtaining both strong granules containing only small amount of fines and tablets of very high hardness % About 10% is to be preferred to achieve proper process times & spray rates 30 minutes By applying the binder solution within 30 minutes strong granules can be obtained, offering a very homogeneous particle size distribution. Spray rate Standard settings as for PVP Generally, the higher the spray rate the less fines. Temperature Standard settings as for PVP Generally, the higher the spray rate the less fines.

13 03_030724e-11 February 2013 Page 13 of 14 Kollicoat IR Equipment & Process Granulator Fluid bed, Glatt GPCG 3 Set up Top spray Nozzle 1.0 mm Sieve Oscillating, Erwekaar 400 Batch volume 5L Batch mass 1150 g Inlet air temperature 60 C Air quantity m 3 /h Spray rate Various Spray pressure 1.5 bar Product temperature Approx. 32 C Process time 30 minutes Sieve 800 µm Properties of the granules Kollicoat IR led to much more homogeneous particle size distribution. Particle size disstribution [-] PVP K25 PVP K90 Kollicoat IR Binder/spray rate [g/min] <125 µm µm >355 µm Kollicoat IR led to the formation of strongest granules due to the reason that it offers elasticity as well as plastic deformation. Result The peroxide free Kollicoat IR is an efficient binder combining low viscosity of the polymer solution and strength of the final agglomerates which in turn led to high tablets hardness.

14 03_030724e-11 February 2013 Page 14 of 14 Kollicoat IR 5. Storage conditions No specific temperature (ambient/room temperature). 6. Stability At least 2 years in the original sealed containers at room temperature. 7. Toxicology A toxicological summary is available on request. 8. PRD-No Packaging 20 kg plastic drum Note This document, or any answers or information provided herein by BASF, does not constitute a legally binding obligation of BASF. While the descriptions, designs, data and information contained herein are presented in good faith and believed to be accurate, it is provided for your guidance only. Because many factors may affect processing or application/use, we recommend that you make tests to determine the suitability of a product for your particular purpose prior to use. It does not relieve our customers from the obligation to perform a full inspection of the products upon delivery or any other obligation. NO WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, ARE MADE REGARDING PRODUCTS DESCRIBED OR DESIGNS, DATA OR INFORMATION SET FORTH, OR THAT THE PRODUCTS, DESIGNS, DATA OR INFORMATION MAY BE USED WITHOUT INFRINGING THE INTELLECTUAL PROPERTY RIGHTS OF OTHERS. IN NO CASE SHALL THE DESCRIPTIONS, INFORMATION, DATA OR DESIGNS PROVIDED BE CONSIDERED A PART OF OUR TERMS AND CONDITIONS OF SALE. February 2013 BASF Nutrition & Health