Direct compression excipient based on lactose

Technical Information

October 2001 (MPM)Supersedes issue of June 1997

File section 9

® = Registered trademark of BASF Aktiengesellschaft

Ludipress�

Fine Chemicals

Nature White, free-flowing granules that are odourless and tasteless.

Specification Lactose monohydrate Ph. Eur. 93.0 %] 2 %Kollidon® 30 USP 93.5 %] 0.5 %Kollidon CL USP 93.5 %] 0.5 %

Total water content $ 6 %(Karl Fischer)Heavy metals $ 10 ppm

The lactose assay is determined by polarimetry, Kollidon CL is determinedgravimetrically, and Kollidon 30 is determined photometrically. The methodsof 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/gYeasts and fungi $ 100/gPathogenic bacteria:

E. coli 0/gPseudomonas aeruginosa 0/gStaphylococcus aureus 0/gSalmonellae 0/10 gOther enterobacteriaceae $ 100/g

Technical properties, The following typical values for the particle size distribution are based on typical values measurements with a sieve shaker.

< 263 µm max. 15 %< 200 µm 40 – 60 %< 400 µm min. 90 %

The bulk and tap densities fall within the following ranges:Bulk density 550] 50 g/lTap density 650] 50 g/l

Hygroscopicity Fig. 1 shows the sorption isotherm for Ludipress, expressed in terms ofthe dry weight. The initial value corresponds practically to the water ofcrystallisation of the lactose.

Fig. 1: Sorption isotherm of Ludipress at 30 °C

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[%]

5

3

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Relative humidity [%]

0 10 20 30 40 50 60 70 80 90

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As Ludipress contains a disintegrant, Kollidon CL that swells on contactwith 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.

Application Ludipress has been specially developed for direct compression, but is alsovery suitable as a filler for hard gelatin capsules.

The following examples of formulations provide a guideline. They werecompressed into tablets on a rotary tablet press using the pressures given.

200

180

160

140

120

80

Har

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s [N

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100

60

40

20

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Compression force [kN]

0 5 10 15 20 25 30

Ludipress (preparation)

Physical mixture

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Acetylsalicylic Acid Tablets (400 mg)

Acetylsalicylic acid, crystalline 400 gLudipress 99 gStearic acid 1 gKollidon CL (BASF) 15 g

Mix all components, pass through a 0.8 mm sieve and press with lowcompression force.

Tablet properties

Weight 516 mgDiameter 12 mmForm biplanarHardness 90 NDisintegration <1 minFriability 0.4 %Dissolution 15 min: 84 %

30 min: 97%

Chemical stability

Storage time RT 40 °C

10 months 100.0 % 100.0 %16 months 100.0 % 100.0 %12 months 198.4 % 99.1%

The content of free salicylic acid always remained below 0.2 %.

ww-Carotene Tablets (15 mg)

w-Carotene dry powder BetaVit® 10 % (BASF) 160.0 gLudipress 240.0 gKollidon CL (BASF) 6.0 gMagnesium stearate 2.0 g

Mix all components, pass through a 0.8 mm sieve and press with mediumcompression force.

Properties

Weight 400 mgDiameter 12 mmForm biplanarHardness 59 NDisintegration 12 minFriability 0.1%

Chemical and physical stability (20 – 25 °C)

6 Months 12 Months

Loss of beta carotene 3.5 % 3.5 %Hardness 60 N 59 NDisintegration 9 min 7 minFriability 0.15 % 0.16 %

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Vitamin E Chewable Tablets (100 mg)

Formulations

Vitamin E acetate Dry Powder SD 50 (BASF) 200 gLudipress 493 gAerosil® 200 7 g

Mix all components, pass through a 0.8 mm screen and press with highcompression force.

Properties

Weight 727 mgDiameter 12 mmForm biplanarHardness 102 NDisintegration 15 minFriability 0 %

Ibuprofen Tablets (400 mg)

I. Ibuprofen 400 gAerosil 200 4 g

II. Ludipress 342 gKollidon CL (BASF) 8 gMagnesium stearate 8 g

Mix I, then add the components of II, and press with low compressionforce.

Properties

Weight 752 mgDiameter 16 mmHardness 112 NDisintegration 2 – 3 minFriability 0.4 %Dissolution, 10 min 82 %

15 min 91%

4. Physical stability

(20 – 25 ºC) 6 Months 8 Months 12 Months

Hardness – 121 N 120 NDisintegration – 2 – 3 min –Friability 0.4 % 0.4 % 0.2 %Dissolution, 10 min 85 % – 89 %

20 min 87% 91% 88 %

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Famotidine Tablets (40 mg)

No. 1 No. 2

Famotidine 40 g 40 gLudipress 105 g 104 gMagnesium stearate 3 g –Stearic acid – 2 gAerosil 200 4 g 4 g

Mix all components, pass through a 0.8 mm sieve and press with lowcompression force.

Properties

No. 1 No. 2

Weight 149 mg 148 mgDiameter 8 mm 8 mmForm biplanar biplanarHardness 74 N 49 NDisintegration (gastric juice) 3 min 1 minFriability < 0.1% 0.3 %Dissolution, 10 min 63 % not tested

30 min 95 % not tested

Glibenclamide Tablets (5 mg), processability of different particlesizes

No. 1 No. 2

Glibenclamide, micronized 5.0 g –Glibenclamide – 5.0 gLudipress 120.0 g 194.0 gMagnesium stearate 0.5 g 1.0 g

Mix all components, pass through a 0.8 mm sieve and press with lowcompression force.

Properties

No. 1 No. 2

Weight 125 mg 201 mgDiameter 7 mm 8 mmForm biplanar biplanarHardness 80 N 107 NDisintegration 2 – 3 min 3 – 4 minFriability < 0.2 % < 0.1%Dissolution, 10 min 50 % –

30 min 69 % –60 min 75 % –

Influence of the compression force on the physical properties of thetablet (Formulation No. 2)

Compression force5 kN 10 kN 20 kN 25 kN

Hardness 47 N 107 N 158 N 191 N

Disintegration 2 – 3 min 3 – 4 min 3 – 4 min 5 min

Friability < 0.1% < 0.1% < 0.1% < 0.1%

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Propranolol Hydrochloride Tablets (10 mg, 50 mg and 100 mg)

No. 1 No. 2 No. 3

Propranolol hydrochloride (BASF) 10 g 50 g 100 gLudipress 490 g 450 g 400 gMagnesium stearate 2.5 g 2.5 g 2.5 g

Mix all components, pass through a 0.8 mm sieve and press with lowcompression force.

Properties

No. 1 No. 2 No. 3

Weight 514 mg 496 mg 505 mgDiameter 12 mm 12 mm 12 mmForm biplanar biplanar biplanarHardness 112 N 86 N 101 NDisintegration 2 min 2 min 3 minFriability 0.1% 0.2 % 0.1%

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) 200.0 gLudipress 256.0 gKollidon VA 64 25.0 gMagnesium stearate 2.5 g

Mix all components, pass through a 0.8 mm sieve and press with mediumcompression force (18 kN).

Properties

No. 2

Weight 499 mgDiameter 12 mmForm biplanarHardness 73 NFriability 0.4 %Dissolution, 30 min > 90 %

Vitamin B Complex + Vitamin C Tablets, Addition of Dry Binder Kollidon VA 64

No. 1 No. 2

Thiamine mononitrate (BASF) 5.0 g –Thiamine hydrochloride (BASF) – 15.0 gRiboflavine (BASF) 5.0 g 2.0 gPyridoxine hydrochloride (BASF) 5.0 g 5.0 gFolic acid 0.5 g –Choline bitartrate – 25.0 gNiacin (nicotinic acid) 30.0 g –Nicotinamide – 10.0 gBiotin 0.1 g –Calcium D-pantothenate (BASF) 10.0 g –Ascorbic acid, powder (BASF) 150.0 g 100.0 gLudipress 172.4 g 220.0 gKollidon VA 64 20.0 g –Magnesium stearate 2.0 g –Stearic acid – 8.0 g

Mix all the ingredients pass through a 0.8 mm sieve and press into tabletswith medium/low compression force.

Properties

No. 1 No. 2

Weight 400 mg 411 mgDiameter 10 mm 12 mmForm biplanar biplanarHardness 95 N 69 NDisintegration 3 – 4 min 5 minFriability 0.1% 0.3 %

Multivitamin Tablets

Vitamin A Acetate Dry Powder 50 000 I. U./g (BASF) 10.0 gThiamine mononitrate (BASF) 2.2 gRiboflavine (BASF) 2.2 gNicotinamide (BASF) 16.5 gCalcium D-pantothenate (BASF) 11.0 gPyridoxine hydrochloride (BASF) 2.2 gCyanocobalamin 0.1% SD (BASF) 6.0 gAscorbic Acid, Powder (BASF) 85.0 gVitamin E Acetate Dry Powder SD50 (BASF) 31.0 gLudipress 321.0 gMagnesium stearate 3.0 gSaccharin sodium 2.5 gOrange flavour 7.2 g

Mix all components, pass through a 0.8 mm sieve and press with mediumcompression force.

Weight 500 mgDiameter 12 mmForm biplanarHardness 68 NDisintegration 5 minFriability 0.2 %

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

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Packaging 20-kg cardboard boxes with liner

Storage Keep containers tightly closed.

Storage stability The shelf life of the product in original unopened containers is at least twoyears if they are properly stored.

Product number 086 160/01

Note The data submitted in this publication are based on our current knowledgeand experience. They do not constitute a guarantee in the legal sense ofthe term and, in view of the manifold factors that may affect processingand application, do not relieve processors from the responsibility of carry-ing out their own tests and experiments. Any relevant patent rights andexisting legislation and regulations must be observed.

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BASF AktiengesellschaftStrategic MarketingPharma Solutions67056 LudwigshafenGermanywww.basf.de/pharmaLudipress® is a registered trademark of BASF Aktiengesellschaft, Germany