Generic Drug Formulations With Kollicoat and Kollidon

Generic Drug Formulations

with

Kollicoat® SR 30 D

and

Kollidon® SR

Generic Drug Formulations with Kollicoat® SR 30 D and Kollidon® SR

Page2/51 MEF/EP076 Contents

Contents

I. Kollicoat® SR 30 D

Coating

1.1 Theophylline sustained-release pellets

1.2 Theophylline sustained-release pellets(drug-layering process)

2. Caffeine sustained-release pellets(extrusion process)

3.1 Propranolol HCl sustained-release pellets(extrusion process)

3.2 Propranolol HCl sustained-release pellets(drug-layering process)

3.2.1 Propranolol HCl pellet-releasing tablet

4. Acetaminophen – taste masked

5. Ibuprofen sustained-release pellets(drug-layering process)

6. Ambroxol HCl sustained-release pellets(drug-layering process)

6.1 Ambroxol HCl pellet-releasing tablet

7. Tramadol HCl sustained-release pellets(drug-layering process)

8. Acetylsalicylic acid crystals



Granulation

9. Propranolol HCl sustained-release tablet

10. Theophylline sustained-release tablet

11. Carbamazepine sustained-release tablet



II. Kollidon® SR

12. Metoprolol tartrate sustained-release tablet


14. Caffeine sustained-release tablet

15. Diclofenac Na sustained-release tablet

16. Ascorbic acid sustained-release tablet

17. Indometacin sustained-release tablet


19. Nifedipine sustained-release tablet

20. Tramadol HCl sustained-release tablet

21. Diltiazem HCl sustained-release tablet

22. Naphtidrofuryl oxalate sustained-releasetablet



Page5/51 Caffeine sustained-release pellets

®



1.1 Theophylline sustained-release pellets

a) Formulation

The formulation is designed for 500g of pure theophylline pellets (Spherofillin [1];diameter 0.8-1.3mm)

Polymer suspension Kollicoat® SR 30 D [1] 223.67gPropylene glycol [1] 6.71gWater 149.86g

Pigment suspension Kollidon® 30 [1] 2.24gTitanium dioxide [2] 2.24gSicovit® Red 30 [1] 2.24gTalc [3] 15.66gWater 44.73g

b) Preparation of the spray suspension

Polymer suspension Add propylene glycol followed by Kollicoat® SR30 D to the given quantity of water with stirring.

Pigment suspension Dissolve Kollidon® 30 in the given quantity ofwater. Add Sicovit® Red 30, titanium dioxide andtalc with vigorous stirring and homogenize themixture in a corundum disk mill.

Spray suspension Incorporate the pigment suspension into thepolymer suspension with stirring. The suspensionmust be stirred during the spraying process toprevent settling.



c) Coating

The pellets were coated in an Aeromatic Strea-1 (Aeromatic AG). The suspensionwas sprayed continuously onto the fluidized, pre-heated pellets from the top.

Process parameters Inlet air temperature 60°COutlet air temperature 37°CProduct temperature 38°CAir flow 80m³/hNozzle diameter 0.8mmSpraying rate approx. 11.5g/minSpraying time 39 minAtomizing pressure 1.0barDrying 45°C/ 5minCoating weight 2mg film former/cm²

The coating weight of 2mg film former / cm² given here was determined from thesurface area of the pellets. Since the particle size distribution and surface structureinfluence the polymer quantity required, calculating the surface area is recommendedas a means of estimating the required coating weight in each specific case.

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0.5 mg Kollicoat SR 30 D/cm² 1.0 mg Kollicoat SR 30 D/cm² 2.0 mg Kollicoat SR 30 D/cm²

method: paddle 50 rpm; 37°C0-2h: 0.08 M HCl2-24h: phosphate buffer pH 6.8



1.2 Theophylline sustained-release pellets(drug-layering process)

a) Formulation

The formulation is designed for 800g of pellets manufactured by drug layering ofnonpareilles.

Polymer suspension Kollicoat® SR 30 D [1] 533.0gTriethyl citrate (TEC) [4] 16.0gWater 433.0g

Pigment suspension Talc [3] 56.0gWater 100.0g


Polymer suspension Add TEC followed by Kollicoat® SR 30 D to thegiven quantity of water with stirring.

Pigment suspension Add talc to the given quantity of water withvigorous stirring.




c) Coating

The pellets were coated in an GPCG1 (Glatt). The suspension was sprayedcontinuously onto the fluidized, pre-heated pellets by the Wurster method.

Process parameters Machine Glatt GPCG1Method Bottom-spray (Wurster)Inlet air temperature 50-55°COutlet air temperature 29-32°CProduct temperature 35-40°CAir flow 90m³/hNozzle diameter 1.2mmSpraying time 260 minSpraying rate approx. 4.5 g/minAtomizing pressure 1.2barDrying 40°C/ 15minCoating weight 20%

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method: paddle 100 rpm; 37°C0-20h: pH 7.4



2. Caffeine sustained-release pellets

a) Formulation

The formulation is designed for 500g of pellets (composition of pellets: 10% caffeine[1], 43.75% Avicel® PH 101 [5], 43.75% lactose [6], 2.5% Kollidon® VA 64 [1];diameter 0.7-1.4mm; made by wet extrusion).


Pigment suspension Kollidon® 30 [1] 2.7gTitanium dioxide [2] 2.7gSicovit® Red 30 [1] 2.7gTalc [3] 18.87gWater 53.89g


Polymer suspension Add propylene glycol followed by Kollicoat® SR 30 Dto the given quantity of water with stirring.

Pigment suspension Dissolve Kollidon® 30 in the given quantity of water.Add Sicovit® Red 30, titanium dioxide and talc withvigorous stirring and homogenize the mixture in acorundum disk mill.

Spray suspension Incorporate the pigment suspension into the polymersuspension with stirring. The suspension must bestirred during the spraying process to prevent settling.



c) Coating


Process parameters Inlet air temperature 60°COutlet air temperature 36°CProduct temperature 37°CAir flow 80m³/hNozzle diameter 0.8mmSpraying rate approx. 12g/minSpraying time 45 minAtomizing pressure 1.0barDrying 45°C/ 5minCoating weight 3mg film former/cm²

The coating weight of 3mg film former / cm² given here was established for thepellets by surface area determination. Since the particle size distribution and surfacestructure influence the required polymer quantity, calculating the surface area isrecommended as a means of estimating the required coating weight in each specificcase.

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Page12/51 Acetminophen – taste masked

3.1 Propranolol HCl sustained-release pellets(extrusion process)

a) Formulation

The formulation is designed for 500g of pellets (composition of pellets: 20%propranolol HCl [1], 51.66% Avicel® PH 101 [5], 25.84% lactose [6], 2.5% Kollidon®

VA 64 [1]; diameter 0.4-1.5mm; made by wet extrusion).)


Talc suspension Talc [3] 29.94gWater 44.91g


Polymer suspension Add propylene glycol followed by Kollicoat® SR30 D to the given quantity of water with stirring.

Talc suspension Add talc with vigorous stirring and homogenizethe mixture in a corundum disk mill.

Spray suspension Incorporate the talc suspension into the polymersuspension with stirring. The suspension must bestirred during the spraying process to preventsettling.



c) Coating


Process parameters Inlet air temperature 60°COutlet air temperature 35°CProduct temperature 36°CAir flow 80m³/hNozzle diameter 0.8mmSpraying rate approx. 13g/minSpraying time 39 minAtomizing pressure 1.0barDrying 45°C/ 5minCoating weight 3mg film former/cm²

The coating weight of 3mg film former / cm² given here was established for thepellets by surface area determination. Since the particle size distribution and surfacestructure influence the required polymer quantity, calculating the surface area isrecommended as a means of estimating the required coating weight in each specificcase.

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3.2 Propranolol HCl sustained-release pellets(drug-layering process)

a) Formulation










c) Coating

The pellets were coated in a Glatt GPCG1 coater. The suspension was sprayedcontinuously onto the fluidized, pre-heated pellets from the bottom by the Wurstermethod. Weight gains of 5, 10, 15 and 20% were tested.


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5% Kollicoat SR 30 D10% Kollicoat SR 30 D15% Kollicoat SR 30 D20% Kollicoat SR 30 D

method: paddle 50 rpm; 37°C0-20h: 0.1M HCl



3.2.1 Propranolol HCl pellet-releasing tablet

a) Formulation

The formulation is designed for 500g of tablets:

Propranolol HCl/ Kollicoat® SR pellets 250.0gMicrocrystalline cellulose (Vivapur® 200) [7] 250.0gMagnesium stearate [8] 2.5g

b) Procedure

Mix the ingredients together, pass through a 0.8mm sieve and compress into tabletswith a force of about 15kN.

Tablet press Korsch EK0, 30 tablets/ minCompression force 15kN

c) Tablet properties

Weight 400mgDiameter 10mmForm biplanarHardness 82-112N

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Tablets 850 - 1000 µmTablets 710 - 850 µmPellets 850 - 1000 µmPellets 710 - 850 µm

method: paddle 100 rpm; 37°Ccoating level: 20%0-20h: 0.1M HCl



4. Acetaminophen - taste masked

a) Formulation

The formulation is designed for 500g of acetaminophen granules [1].

Polymer suspension Kollicoat® SR 30 D [1] 73.33g


The dispersion is used directly without any additives.

c) Coating

The crystals were coated in an Aeromatic Strea-1 (Aeromatic AG). The dispersionwas sprayed continuously onto the fluidized, pre-heated crystals from the top.

Process parameters Inlet air temperature 60°COutlet air temperature 40°CProduct temperature 41°CAir flow 80m³/hNozzle diameter 0.8mmSpraying rate approx. 9g/minSpraying time 9 minAtomizing pressure 1.0barDrying 45°C/ 5minCoating weight 4%

Crystalline acetaminophen is coated with 4% Kollicoat® SR 30 D.



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0.1N HClphosphate buffer pH 6.8


Page19/51 Ibuprofen sustained-release pellets

5. Ibuprofen sustained-release pellets(drug-layering process)


a) Subcoating

The polymer spray solution for a weight gain of 5%:

Spray solution Mowiol® 4-88 (PVA) [9] 48.0gWater 432.0g

b) Preparation of the spray solution (subcoating)

Dissolve Mowiol in hot water and cool with stirring.

Process parameters Machine Glatt GPCG1Method Bottom-spray (Wurster)Inlet air temperature 50°COutlet air temperature 35°CProduct temperature 40°CAir flow 80m³/hNozzle diameter 1.2mmSpraying time 56 minSpraying rate approx. 3.1g/minAtomizing pressure 1.2barDrying 40°C/ 15minSubcoating weight 5%

c) Polymer coating

The formulation is designed for 800g of subcoated pellets.




Page20/51 Ibuprofen sustained-release pellets

d) Preparation of the spray suspension (polymer coating):




Process parameters Machine Glatt GPCG1Method Bottom-spray (Wurster)Inlet air temperature 50-55°COutlet air temperature 29-32°CProduct temperature 35-40°CAir flow 90m³/hNozzle diameter 1.2mmSpraying time 230 minSpraying rate approx. 4.5 g/minAtomizing pressure 1.2barDrying 40°C/ 15min

Spray the suspension continuously onto fluidized pre-heated pellets by the wursterspray method. Weight gains 5, 10, 15 and 20%.

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5% Kollicoat SR 30D10% Kollicoat SR 30D15% Kollicoat SR 30D20% Kollicoat SR 30D



Page21/51 Ambroxol HCl sustained-release pellets

6. Ambroxol HCl sustained-release pellets(drug-layering process)


a) Formulation







c) Coating




Process parameters Machine Glatt GPCG1Method Bottom-spray (Wurster)Inlet air temperature 50-55°COutlet air temperature 29-32°CProduct temperature 35-40°CAir flow 90m³/hNozzle diameter 1.2mmSpraying time 220 minSpraying rate approx. 4.5 g/minAtomizing pressure 1.2barDrying 40°C/ 15minWeight gain 20%

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6.1 Ambroxol HCl pellet-releasing tablet

d) Formulation

The formulation is designed for 500g of tablets:

Ambroxol HCl/ Kollicoat® SR pellets 250.0gMicrocrystalline cellulose (Vivapur® 200) [7] 250.0gMagnesium stearate [8] 2.5g

e) Procedure


Tablet press Korsch EK0, 30 tablets/ minCompression force 15kN

f) Tablet properties

Weight 400mgDiameter 10mmForm biplanarHardness 92-116N

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Page24/51 Tramadol HCl sustained-release pellets

7. Tramadol HCl sustained-release pellets(drug-layering process)

a) Polymer coating








c) Coating



Page25/51 Tramadol HCl sustained-release pellets

Process parameters Machine Glatt GPCG1Method Bottom-spray (Wurster)Inlet air temperature 50-55°COutlet air temperature 29-32°CProduct temperature 35-40°CAir flow 90m³/hNozzle diameter 1.2mmSpraying time 225 minSpraying rate approx. 4.5 g/minAtomizing pressure 1.2barDrying 40°C/ 15minWeight gain 20%

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tablets, 15% Kollicoat SR 30 Dtablets, 20% Kollicoat SR 30 Dpellets, 15% Kollicoat SR 30 Dpellets, 20% Kollicoat SR 30 D



Page26/51 Acetylsalicylic acid crystals

8. Acetylsalicylic acid crystals

a) Formulation

The formulation is designed for 800g of acetylicsalicylic acid crystals [12].

Spray suspension Kollicoat® SR 30 D [1] 666.25gTalc [3] 70.00gWater 666.25g


Add talk to the given amount of water with vigorous stirring.Then add Kollicoat SR 30 D with slow stirring.

c) Coating

The crystals were coated in a Glatt GPCG1 coater. The suspension was sprayedcontinously onto the fluidized, pre-heated crystals by the Wurster method. Weightgains of 5, 10, 15 and 20% were tested.



Page27/51 Acetylsalicylic acid crystals

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crystals10% Kollicoat SR 30D15% Kollicoat SR 30D20% Kollicoat SR 30D25% Kollicoat SR 30D

method: paddle 100 rpm; 37°C0-20h: pH 7.4no plasticizer


Page28/51 Kollicoat® SR 30 D - Granulation


Page29/51 Propranolol HCl sustained-release tablet


a) Formulation of the granules

Propranolol HCl Powder 80 [1] 250.0gGranulac® 140 (lactose) [6] 100.0g

Kollicoat® SR 30 D [1] 525.0g

b) Manufacture of the granules

The active ingredient and excipient were granulated in an Aeromatic Strea-1(Aeromatic AG). The polymer dispersion was sprayed into the fluid bed from the top.

Process parameters Inlet air temperature 55°COutlet air temperature 22 – 27°CNozzle diameter 1.2mmSpraying rate approx. 10g/minAtomizing pressure 2.0bar

c) Formulation of the tablets

Propranolol HCl powder 80 [1] 160.0mgKollicoat® SR 30 D [1] 96.0mgGranulac® 140 [6] 64.0mgAerosil® 200 [13] 1.6mgMagnesium stearate [8] 1.6mg

d) Tableting

The granules were passed together with magnesium stearate (0.5%) and Aerosil®200 (0.5%) through an 800µm sieve, blended for 10 min in a Turbula mixer andcompressed into tablets with a force of about 18kN.

Tablet press Korsch EK0, 30 tablets/ minCompression force 17.7kN



e) Tablet properties

Weight 323.0mgDiameter 10mmForm biplanarHardness 260N

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Page31/51 Theophylline sustained-release tablet



Theophylline powder [1] 250.0gGranulac® 140 [6] 212.5g



The active ingredient and excipient was granulated in an Aeromatic Strea-1(Aeromatic AG). The polymer dispersion was sprayed into the fluid bed from the top.



Theophylline pdr [1] 400.0mgKollicoat® SR 30 D [1] 60.0mgGranulac® 140 [6] 340.0mgAerosil® 200 [13] 4.0mgMagnesium stearate [8] 4.0mg

d) Tableting


Tablet press Korsch PH 106, 30 rpmCompression force 18.7kN




Weight 808.0mgDiameter football shape 19.0x8.5mmHardness 276N

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Page33/51 Carbamazepine sustained-release tablet



Carbamazepine [14] 250.0gGranulac® 140 [6] 185.3gKollidon® CL-M [1] 25.3g



The active ingredient and excipients were granulated in an Aeromatic Strea-1(Aeromatic AG). The polymer dispersion was sprayed into the fluid bed from the top.



Carbamazepine [14] 200.0mgKollicoat® SR 30 D [1] 30.0mgKollidon® CL-M [1] 20.2mgGranulac® 140 [6] 149.8mgAerosil® 200 [13] 2.0mgMagnesium stearate [8] 2.0mg

d) Tableting






Weight 404.0mgDiameter 11mmForm biconvexHardness 136N

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method: paddle 50 rpm; 37°C0-16h: SDS-solution (1%; water)


Page35/51 Kollidon SR

®


Page36/51 Metoprolol tartrate sustained-release tablet

12. Metoprolol tartrate sustained-release tablet


Metoprolol tartrate [15] 454.5gKollicoat® SR 30 D [1] 45.5g


The active ingredient was granulated in an Aeromatic Strea-1 (Aeromatic AG). Thepolymer dispersion was sprayed into the fluid bed from the top.



Metoprolol tartrate [15] 200.0mgKollicoat® SR 30 D solid polymer 6.0mgKollidon® SR [1] 250.0mgMagnesium stearate [8] 2.5mg

d) Tableting

The granules were passed together with magnesium stearate (0.5%) and Kollidon®

SR (54.5%) through an 800µm sieve, blended for 10 min in a Turbula mixer andcompressed into tablets with a force of about 10kN.

Tablet press Korsch EK0, 30 tablets/ minCompression force 9,3kN


Page37/51 Metoprolol tartrate sustained-release tablet



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a) Formulation

Propranolol HCl [1] 160.0mgKollidon® SR [1] 160.0mgAerosil® 200 [13] 3.4mgMagnesium stearate [8] 1.6mg

b) Procedure

Mix the ingredients together, pass through a 0.8mm sieve and compress intotablets with a force of about 10kN.

Tablet press Korsch PH 100/6 30 rpmCompression force 9,9kN



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Page39/51 Caffeine sustained-release tablet

14. Caffeine sustained-release tablet

a) Formulation

Caffeine gran. 0,2/0,5 [1] 160.0mg 160.0mg 160.0mgKollidon® SR [1] 160.0mg 120.0mg 80.0mgAvicel® PH 102 [5] -- 40.0mg 80.0mgMagnesium stearate [8] 1.6mg 1.6mg 1.6mg

b) Procedure


Tablet press Korsch PH100/6, 30 rpmCompression force 9.6kN 9.8kN 10.1kN


Weight 322.0mg 322.0mg 322.0mgDiameter 10mm 10mm 10mmForm biplanarHardness 213N 201N 193NFriability <0.1% <0.1% <0.1%

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caffeine/ Kollidon SR (160mg/ 80mg)





Page40/51 Caffeine sustained-release tablet

15. Diclofenac Na sustained-release tablet

a) Formulation

Diclofenac Na [16] 100.0mg 100.0mgKollidon® SR [1] 100.0mg 150.0mgAerosil® 200 [13] 3.4mg 3.4mgMagnesium stearate [8] 3.0mg 3.0mg

b) Procedure


Tablet press Korsch EK0, 30 tablets/ minCompression force 7.9kN 7.0kN


Weight 206.0mg 256.0mgDiameter 8mmForm biplanarHardness 195N 229NFriability <0.1% <0.1%

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diclofenac Na/ Kollidon SR (100mg/ 100mg)

diclofenac Na/ Kollidon SR (100mg/ 150mg)

method: paddle 50 rpm; 37°C0-16h: phosphate buffer pH 6.8



16. Ascorbic acid sustained-release tablet

a) Formulation

Ascorbic acid cryst. [1] -- 200.0mg 200.0mgAscorbic acid pdr. [1] 200.0mg -- --Kollidon® SR [1] 200.0mg 200.0mg 280.0mgLudipress® LCE [1] 75.0mg 80.0mg --Aerosil® 200 [13] 5.0mg -- --Magnesium stearate [8] 9.0mg 9.0mg 9.0mg

b) Procedure


Tablet press Korsch EK0, 30 tablets/ minCompression force 17.1kN 20.0kN 18.6kN


Weight 489.0mg 489.0mg 489.0mgDiameter 12mmForm biplanarHardness 164N 140N 151NFriability 0.1% 0.1% 0.2%

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ascorbic acid plv./ K.SR/ L.LCE (200mg/ 200mg/ 75mg)

ascorbic acid cryst./ K.SR/ L.LCE (200mg/ 200mg/ 80mg)

ascorbic acid cryst./ K.SR/ L.LCE (200mg/ 200mg/ 80mg)

method: paddle 50 rpm; 37°C0-24h: phosphate buffer pH 4.0(1% cysteine HCl-solution)



17. Indometacin sustained-release tablet

a) Formulation

Indometacin [12] 75.0mg 75.0mgKollidon® SR [1] 125.0mg 125.0mgLudipress® LCE [1] 100.0mg --Aerosil® 200 [13] 1.5mg 4.0mgMagnesium stearate [8] 1.5mg 2.0mg

b) Procedure




Weight 303.0mg 203.0mgDiameter 10mmForm biplanarHardness 163N 133NFriability <0.1% 0.1%

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indometacin/ K.SR (75mg/ 125 mg)

indometacin/ K.SR/L.LCE (75mg/ 125mg/100mg)

method: paddle 50 rpm; 37°C0-16h: phosphate buffer pH 7.2




a) Formulation

Carbamazepine [14] 200.0mg 200.0mgKollidon® SR [1] 100.0mg 100.0mgLudipress® LCE [1] 200.0mg 150.0mgKollidon® CL-M [13] -- 20.0mgMagnesium stearate [8] 2.5mg 2.5mg

b) Procedure




Weight 503.0mg 473.0mgDiameter 12mmForm biplanarHardness 146N 164NFriability 0.1% <0.1%

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carbamazepine/ K. SR/ L. LCE (200mg/ 100mg/ 200mg)

carbamazepine/ K. SR/ L. LCE/ K. CL-M (200mg/ 100mg/ 150mg/ 20mg)

method: paddle 75 rpm; 37°C0-16h: SDS-solution (1%; water)


Page44/51 Nifedipine sustained-release tablet

19. Nifedipine sustained-release tablet

a) Formulation

Nifedipine [17] 20.0mgKollidon® SR [1] 100.0mgLudipress® LCE [1] 100.0mgMagnesium stearate [8] 1.0mg

b) Procedure




Weight 221.0mgDiameter 8mmForm biplanarHardness 193NFriability <0.1%

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method: paddle 100 rpm; 37°C0-24h: phosphate buffer 6.8/0.5% SDS


Page45/51 Tramadol HCl sustained-release tablet

20. Tramadol HCl sustained-release tablet

a) Formulation

Tramadol HCl [11] 100.0mgKollidon® SR [1] 150.0mgAerosil® 200 [13] 2.5mgMagnesium stearate [8] 1.5mg

b) Procedure





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Page46/51 Diltiazem HCl sustained-release tablet

21. Diltiazem HCl sustained-release tablet

a) Formulation

Diltiazem HCl [18] 120.0mgKollidon® SR [1] 180.0mgAerosil® 200 [13] 3.0mgMagnesium stearate [8] 1.5mg

b) Procedure





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method: paddle 100 rpm; 37°C0-16h: deionized water


Page47/51 Naphtidrofuryl oxalate sustained-release tablet

22. Naphtidrofuryl oxalate sustained-release tablet

a) Formulation

Naphtidrofuryl oxalate [18] 100.0mgKollidon® SR [1] 150.0mgTalc [3] 25.0mgAerosil® 200 [13] 5.4mgMagnesium stearate [8] 2.5mg

b) Procedure


Tablet press Korsch PH106, 30 rpmCompression force 17.0kN



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a) Formulation

Theophylline pdr. [1] 500.0mgKollidon® SR [1] 200.0mgLudipress® LCE [1] 225.0mgMagnesium stearate [8] 3.0mg

b) Procedure


Tablet press Korsch PH 106, 30 rpmCompression force 10.8kN


Weight 928.0mgDiameter 19.0x8.5mmForm football shapeHardness 172NFriability <0.1%

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Page49/51 Substances

Substances[1] BASF Aktiengesellschaft Excipients

Carl-Bosch Str. 38 Kollicoat® SR 30 D67056 Ludwigshafen, Germany Kollidon® 30

Kollidon® CLKollidon® CL-MKollidon® SRKollidon® VA 64Ludipress® LCEPropylene glycolSicovit® Red 30

ActivesAcetaminophen gran.Ascorbic acid cryst.Ascorbic acid powderCaffeine gran. 0.2/0.5IbuprofenPropranolol HCl powder 80Theophylline powderSpherofillin

[2] Kronos Titan GmbH Titanium dioxidePostfach 10072051307 Leverkusen, Germany

[3] Riedel-de-Haën AG TalcWunstdorferstr. 4030926 Seelze, Germany

[4] Merck-Schuchardt Triethyl citrate85662 Hohenbrunn, Germany

[5] FMC Corp. Food + Pharmaceutical Avicel® PH 101Products Avicel® PH 102735 Market StreetPhiladelphia, PA 19103, USA

[6] Meggle Milchindustrie Granulac® 140Postfach 40 Granulac® 23083512 Wasserburg, Germany

[7] J. Rettenmaier & Söhne Vivapur® 200Holzmühle 173494 Rosenberg, Germany

[8] Bärlocher GmbH Magnesium stearate80992 Munich, Germany


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[9] Clariant GmbH Mowiol® 4-88 PVADivision CP/TQM-QP65926 Frankfurt am Main, Germany

[10] Heumann Pharma GmbH Ambroxol HClPostfach 226090008 Nuremberg, Germany

[11] Chemagis Ltd. Tramadol HClP.O. Box 9091Tel Aviv 61090, Israel

[12] Synopharm GmbH Acetylicsalicylic acid crystalsPostfach 1205 Indometacin22882 Barsbüttel, Germany

[13] Degussa-Hüls AG Aerosil® 200Weissfrauenstr. 960287 Frankfurt, Germany

[14] Fabbrica Italiana Sintetici S.p.A. CarbamazepineViale Milano, 2636041 Alte di Montecclio Maggiore,Italy

[15] Moehs S.A. Metoprolol tartrateApartado 5908191 Rubi, Spain

[16] Irotec Laboratories Diclofenac NaLittle Island, Cork, Ireland

[17] Prosintex Industrie ChimicheItaliano

Nifedipine

Via E. Ferm, 20/2620019 Seltimo Milanese (Mi), Italy

[18] Farmak a.s. Diltiazem HClNa Vlcinci 3 Naphtidrofuryl oxalate77117 Olomouc, Czech Republic


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Note

The data submitted in this publication are based on our current knowledge andexperience. They do not constitute a guarantee in the legal sense of the term and, inview of the mainfold factors that may effect processing and application, do not relieveprocessors from the responsibility of carrying out their own tests and experiments.Any relevant patent rights and existing legislation and regulations must be observed.

BASF AktiengesellschaftUnternehmensbereich Fine Chemicals67056 Ludwigshafen, Germany

Generic Drug Formulations With Kollicoat and Kollidon

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