Technical Information

October 2001 (MPM) Supersedes issue of June 1997

Ludipress

File section 9

= Registered trademark of BASF Aktiengesellschaft

Direct compression excipient based on lactose

Fine Chemicals

Nature Specification

White, free-flowing granules that are odourless and tasteless. Lactose monohydrate Kollidon 30 Kollidon CL Total water content (Karl Fischer) Heavy metals Ph. Eur. USP USP $6% $ 10 ppm 93.0 % ] 2 % 93.5 % ] 0.5 % 93.5 % ] 0.5 %

The lactose assay is determined by polarimetry, Kollidon CL is determined gravimetrically, and Kollidon 30 is determined photometrically. The methods of analysis are available on request. Microbial status The microbial status is determined according to the European Pharmacopoeia, Category 3, and complies with the following limits: Mesophilic aerobic bacteria $ 1000/g Yeasts and fungi $ 100/g Pathogenic bacteria: E. coli 0/g Pseudomonas aeruginosa 0/g Staphylococcus aureus 0/g Salmonellae 0/10 g Other enterobacteriaceae $ 100/g The following typical values for the particle size distribution are based on measurements with a sieve shaker. < 263 m max. 15 % < 200 m 40 60 % < 400 m min. 90 % The bulk and tap densities fall within the following ranges: Bulk density 550 ] 50 g/l Tap density 650 ] 50 g/l Hygroscopicity Fig. 1 shows the sorption isotherm for Ludipress, expressed in terms of the dry weight. The initial value corresponds practically to the water of crystallisation of the lactose. 10 9 8 7 6 5 4 3 2 1 0

Technical properties, typical values

Water absorbed [%]

10

20

30

40

50

60

70

80

90

Relative humidity [%] Fig. 1: Sorption isotherm of Ludipress at 30 C

As Ludipress contains a disintegrant, Kollidon CL that swells on contact with water, the surface of tablets made with Ludipress may develop irregularities if they are exposed to high humidities for long periods. Tabletting properties Fig. 2 compares the properties of tablets made with Ludipress and with a physical mixture of the same composition as a function of the compression force. 200 Ludipress (preparation) 180 160 140 120 100 80 Physical mixture 60 40 20 0

Hardness [N]

10

15

20

25

30

Compression force [kN]

Application

Ludipress has been specially developed for direct compression, but is also very suitable as a filler for hard gelatin capsules. The following examples of formulations provide a guideline. They were compressed into tablets on a rotary tablet press using the pressures given.

Acetylsalicylic Acid Tablets (400 mg) Acetylsalicylic acid, crystalline Ludipress Stearic acid Kollidon CL (BASF) 400 99 1 15 g g g g

Mix all components, pass through a 0.8 mm sieve and press with low compression force. Tablet properties Weight Diameter Form Hardness Disintegration Friability Dissolution Chemical stability Storage time 10 months 16 months 12 months RT 100.0 % 100.0 % 198.4 % 40 C 100.0 % 100.0 % 99.1% 516 mg 12 mm biplanar 90 N <1 min 0.4 % 15 min: 84 % 30 min: 97 %

The content of free salicylic acid always remained below 0.2 %. w -Carotene Tablets (15 mg) w-Carotene dry powder BetaVit 10 % (BASF) Ludipress Kollidon CL (BASF) Magnesium stearate 160.0 240.0 6.0 2.0 g g g g

Mix all components, pass through a 0.8 mm sieve and press with medium compression force. Properties Weight Diameter Form Hardness Disintegration Friability 400 mg 12 mm biplanar 59 N 12 min 0.1%

Chemical and physical stability (20 25 C) 6 Months Loss of beta carotene Hardness Disintegration Friability 3.5 % 60 N 9 min 0.15 % 12 Months 3.5 % 59 N 7 min 0.16 %

Vitamin E Chewable Tablets (100 mg) Formulations Vitamin E acetate Dry Powder SD 50 (BASF) Ludipress Aerosil 200 200 g 493 g 7g

Mix all components, pass through a 0.8 mm screen and press with high compression force. Properties Weight Diameter Form Hardness Disintegration Friability 727 mg 12 mm biplanar 102 N 15 min 0%

Ibuprofen Tablets (400 mg) I. Ibuprofen Aerosil 200 II. Ludipress Kollidon CL (BASF) Magnesium stearate 400 g 4g 342 g 8g 8g

Mix I, then add the components of II, and press with low compression force. Properties Weight Diameter Hardness Disintegration Friability Dissolution, 10 min 15 min 4. Physical stability (20 25 C) Hardness Disintegration Friability Dissolution, 10 min 20 min 6 Months 0.4 % 85 % 87 % 8 Months 121 N 2 3 min 0.4 % 91% 12 Months 120 N 0.2 % 89 % 88 % 752 mg 16 mm 112 N 2 3 min 0.4 % 82 % 91%

Famotidine Tablets (40 mg) No. 1 Famotidine Ludipress Magnesium stearate Stearic acid Aerosil 200 40 g 105 g 3g 4g No. 2 40 g 104 g 2g 4g

Mix all components, pass through a 0.8 mm sieve and press with low compression force. Properties No. 1 Weight Diameter Form Hardness Disintegration (gastric juice) Friability Dissolution, 10 min 30 min 149 mg 8 mm biplanar 74 N 3 min < 0.1% 63 % 95 % No. 2 148 mg 8 mm biplanar 49 N 1 min 0.3 % not tested not tested

Glibenclamide Tablets (5 mg), processability of different particle sizes No. 1 Glibenclamide, micronized Glibenclamide Ludipress Magnesium stearate 5.0 g 120.0 g 0.5 g No. 2 5.0 g 194.0 g 1.0 g

Mix all components, pass through a 0.8 mm sieve and press with low compression force. Properties No. 1 Weight Diameter Form Hardness Disintegration Friability Dissolution, 10 min 30 min 60 min 125 mg 7 mm biplanar 80 N 2 3 min < 0.2 % 50 % 69 % 75 % No. 2 201 mg 8 mm biplanar 107 N 3 4 min < 0.1%

Influence of the compression force on the physical properties of the tablet (Formulation No. 2) 5 kN Hardness Disintegration Friability 47 N 2 3 min < 0.1% Compression force 10 kN 20 kN 107 N 3 4 min < 0.1% 158 N 3 4 min < 0.1% 25 kN 191 N 5 min < 0.1%

Propranolol Hydrochloride Tablets (10 mg, 50 mg and 100 mg) No. 1 Propranolol hydrochloride (BASF) Ludipress Magnesium stearate 10 g 490 g 2.5 g No. 2 50 g 450 g 2.5 g No. 3 100 g 400 g 2.5 g

Mix all components, pass through a 0.8 mm sieve and press with low compression force. Properties No. 1 Weight Diameter Form Hardness Disintegration Friability Remarks The amount of Ludipress in formulations 1 and 2 can be reduced. These formulations are also suitable for tablet cores. Vitamin C Tablets (200 mg) with added dry binder Kollidon VA 64 No. 2 Ascorbic acid, powder (BASF) Ludipress Kollidon VA 64 Magnesium stearate 200.0 256.0 25.0 2.5 g g g g 514 mg 12 mm biplanar 112 N 2 min 0.1% No. 2 496 mg 12 mm biplanar 86 N 2 min 0.2 % No. 3 505 mg 12 mm biplanar 101 N 3 min 0.1%

Mix all components, pass through a 0.8 mm sieve and press with medium compression force (18 kN). Properties No. 2 Weight Diameter Form Hardness Friability Dissolution, 30 min 499 mg 12 mm biplanar 73 N 0.4 % > 90 %

Vitamin B Complex + Vitamin C Tablets, Addition of Dry Binder Kollidon VA 64 No. 1 Thiamine mononitrate (BASF) Thiamine hydrochloride (BASF) Riboflavine (BASF) Pyridoxine hydrochloride (BASF) Folic acid Choline bitartrate Niacin (nicotinic acid) Nicotinamide Biotin Calcium D-pantothenate (BASF) Ascorbic acid, powder (BASF) Ludipress Kollidon VA 64 Magnesium stearate Stearic acid 5.0 g 5.0 g 5.0 g 0.5 g 30.0 g 0.1 g 10.0 g 150.0 g 172.4 g 20.0 g 2.0 g No. 2 15.0 g 2.0 g 5.0 g 25.0 g 10.0 g 100.0 g 220.0 g 8.0 g

Mix all the ingredients pass through a 0.8 mm sieve and press into tablets with medium/low compression force. Properties No. 1 Weight Diameter Form Hardness Disintegration Friability Multivitamin Tablets Vitamin A Acetate Dry Powder 50 000 I. U./g (BASF) Thiamine mononitrate (BASF) Riboflavine (BASF) Nicotinamide (BASF) Calcium D-pantothenate (BASF) Pyridoxine hydrochloride (BASF) Cyanocobalamin 0.1% SD (BASF) Ascorbic Acid, Powder (BASF) Vitamin E Acetate Dry Powder SD50 (BASF) Ludipress Magnesium stearate Saccharin sodium Orange flavour 10.0 2.2 2.2 16.5 11.0 2.2 6.0 85.0 31.0 321.0 3.0 2.5 7.2 g g g g g g g g g g g g g 400 mg 10 mm biplanar 95 N 3 4 min 0.1% No. 2 411 mg 12 mm biplanar 69 N 5 min 0.3 %

Mix all components, pass through a 0.8 mm sieve and press with medium compression force. Weight Diameter Form Hardness Disintegration Friability 500 mg 12 mm biplanar 68 N 5 min 0.2 %

Further formulations are given in the compendium, Generic Drug Formulations. This is available on CD-ROM and as a loose-leaf binder from local BASF offices and agencies.

Packaging Storage Storage stability Product number Note

20-kg cardboard boxes with liner Keep containers tightly closed. The shelf life of the product in original unopened containers is at least two years if they are properly stored. 086 160/01 The data submitted in this publication are based on our current knowledge and experience. They do not constitute a guarantee in the legal sense of the term and, in view of the manifold factors that may affect processing and application, do not relieve processors from the responsibility of carrying out their own tests and experiments. Any relevant patent rights and existing legislation and regulations must be observed.

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Ludipress is a registered trademark of BASF Aktiengesellschaft, Germany

BASF Aktiengesellschaft Strategic Marketing Pharma Solutions 67056 Ludwigshafen Germany www.basf.de/pharma

MEFM 08014e