September 2005

Technical Newsletter
Page 1

Content

page

Applications .........................................1 Chemical Nomenclature.........................1 Regulatory.............................................1 How does EMCOMPRESS Improve Tablet Matrices in a Blend with Microcrystalline Cellulose ? ............................................2 EMCOMPRESS in Combination with a Swelling Superdisintegrant .....................2 Flowability .............................................2 Typical Use Level ....................................2 Typical EMCOMPRESS Formulations ......3 Differences between EMCOMPRESS and ANHYDROUS EMCOMPRESS ..................4 Particle size ...........................................4 Binding properties .................................4 Crystal Structure and Application............4 Literature about EMCOMPRESS ............4 Incompatibilities ....................................4

EMCOMPRESS
The ideal flow enhancer from a mineral source. A filler for wet granulation and direct compression. Great synergistic effect when used in combination with Microcrystalline Cellulose.

EMCOMPRESS CaHPO4 * 2 H2O ANHYDROUS EMCOMPRESS CaHPO4

Application in Pharmaceutical Formulations

Both EMCOMPRESS and ANHYDROUS EMCOMPRESS are used in solid dosage forms to enhance flow, as a tablet binder or as a capsule diluent. As a binder, it is used because of its excellent flow properties and deformation characteristic. EMCOMPRESS Calciumhydrogenphosphate (Dibasic Calcium Phosphate, DCP), deforms by brittle fracture during compression. EMCOMPRESS particles fragment into smaller particles exposing less lubricant surface for improved tablet binding. Hence, Magnesium Stearate has almost no influence on the hardness and dissolution times of EMCOMPRESS tablets. Additionally as a consequence of this behaviour, there are no capping problems in tablets made with Calciumhydrogenphosphate. Another EMCOMPRESS benefit, due to its compaction mechanism, is its reduced sensitivity to tableting speed. Also, EMCOMPRESS and lactose possess similar galenic properties, therefore, EMCOMPRESS can be used in place of lactose during formulation development. EMCOMPRESS is typically applied in direct compression and is used as a calcium and phosphorous source in nutritional supplements.

Chemical Nomenclature:
Chemical Nomenclature: Chemical name Synonymes Formula Molecular weight CAS Registry Number
Table 1

EMCOMPRESS Calciumhydrogenphosphate dihydrate Dibasic calcium phosphate dihydrate Calcium monohydrogen phosphate dihydrate Dicalcium orthophosphate dihydrate CaHPO4 * 2 H2O 172.1 7789-77-7

ANHYDROUS EMCOMPRESS Calciumhydrogenphosphate Anhydrous dibasic calcium phosphate Calcium monohydrogen phosphate Dicalcium orthophosphate dihydrate CaHPO4 136.1 7757-93-9

Regulatory:
EMCOMPRESS is listed in the Ph.Eur. and USP/NF. E Classification E 341.
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September 2005
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Technical Newsletter

Applications:
How does EMCOMPRESS Improve Tablet Matrices in a Blend with Microcrystalline Cellulose ?
EMCOMPRESS is often blended with VIVAPUR MCC or EMCOCEL MCC to create a synergistic combination. The combination of brittle fracture and plastic deformation properties results in flowability and compaction, which is greater than the individual components.

Flowability
EMCOMPRESS is widely used in formulations due to its excellent flow properties. Angle of repose is one method used to compare flow properties of different materials. Relationship between angle of repose and flow: Angle of repose Flow < 33 excellent flowability 33 - 38 good flow 38 - 44 problematic >44 not recommended for direct compression

MCC particles (plastic)

EMCOMPRESS particles (brittle fracture)

Table 2

Fig. 1 : Tablet matrix after compression with MCC and EMCOMPRESS .

EMCOMPRESS in Combination with a Swelling Superdisintegrant

A swelling superdisintegrant requires some resistance in the tablet matrix to develop its full disintegrating force. EMCOMPRESS , because it is insoluble and non-elastic, provides such resistance. Soluble materials, such as lactose, do not offer such resistance and, consequently, disintegrate much slower.
water-soluble lactose disintegrant EMCOMPRESS (Calcium Hydrogen Phosphate Dihydrate)

EMCOMPRESS ANHYDROUS EMCOMPRESS Fast Flow Lactose other Lactose Sugar Ibuprofen CaCO3 Powder Corn Starch
Table 3

31 28 31 32 - 35 31 47 50 56

Typical Use Level

as a Tablet binder: as a Diluent: as a Capsule filler:
Table 4

20 - 70 % 10 - 80 % 10 - 50 %

In combination with Microcrystalline Cellulose, EMCOMPRESS use level depends on Microcrystalline Cellulose grade and total formulation composition. To improve flowability, the following ratios have been demonstrated effective: VIVAPUR 101 or EMCOCEL 50M : EMCOMPRESS 40 : 60 VIVAPUR 102 or EMCOCEL 90M : EMCOMPRESS 50 : 50
Table 5

disolve swelling

remove

Fig. 2 : The swelling disintegrant (blue) deforms a plastic particle (brown) but disintegrates EMCOMPRESS a non-elastic particle (red).

To improve compaction, the following ratio has been demonstrated effective: VIVAPUR 101 or VIVAPUR 102 : EMCOMPRESS EMCOCEL 50M or EMCOCEL 90M : EMCOMPRESS 75 : 25
Table 6

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Typical EMCOMPRESS Formulations:

The proposal below is a tablet matrix for fast disintegrating tablets. The Calciumhydrogenphosphate gives the non-water soluble, non-elastic part of the matrix, which in combination with disintegrants reduces the disintegration time significantly. VIVAPUR / EMCOCEL Microcrystalline Cellulose (Binder) EMCOMPRESS CaHPO4 * 2 H2 0 (Filler) EXPLOTAB / VIVASTAR Sodium Starch Glycolate (Superdisintegrant) PRUV Sodium Stearyl Fumarate (Lubricant)
Table 7

An example for a low dose active substance in combination with Microcrystalline Cellulose and EMCOMPRESS : Diclofenac VIVAPUR 102 (Microcrystalline Cellulose) EMCOMPRESS (CaHPO4 * 2 H2 0) VIVASTAR (Sodium Starch Glycolate) Colloidal Silicone Dioxid Magnesium Stearate Diameter Weight Hardness Friability Disintegration time
Table 9

65.0 % 33.0 % 1.5 % 0.5 %

10.0 mg 31.3 mg 77.2 mg 5.3 mg 0.6 mg 0.6 mg 7 mm 125 mg 6.8 kp 0.4 % 103 sec

By using PRUV (Sodium Stearyl Fumarate) instead of Magnesium Stearate as a lubricant the resulting matrix is more hydrophyllic. In a matrix with PRUV, water can penetrate faster than into a lipophyllic matrix. In combination with EMCOMPRESS , a waterinsoluble, non-elastic material, the disintegration time improves significantly. This is a typical combination of Microcrystalline Cellulose and Calciumhydrogenphosphate. EMCOMPRESS improves the flow and VIVAPUR (Microcrystalline Cellulose) provides the hardness.

The active ingredient and binders, disintegrants were mixed for 15 minutes in a Turbula mixer. The sieved blend of Magnesium Stearate and Colloidal Silicone Dioxid was added and mixed for another 5 minutes. The powder was directly compressed on a Korsch EK0 tablet press.

Dissolution profile: Ascorbic acid VIVAPUR 102 (Microcrystalline Cellulose) EMCOMPRESS (CaHPO 4 * 2 H 2O) VIVASOL (Croscarmellose Sodium) Colloidal Silicone Dioxid Magnesium Stearate Diameter Height Weight Compression Force Hardness Disintegration time
Table 8

55.0 20.0 22.0 2.0 0.5 0.5

% % % % % %

100 80

dissolved (%)

60 40 20 0

Dicofenac Tablet
0
10 20 30 40 50 60 70 80

13 mm 4 mm 800 mg 26 kN 7 kp 16 sec

time (min) Fig. 3

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Crystal Structure and Application
ANHYDROUS EMCOMPRESS, which has no crystall water, is less sensitive to interactions with gelatine capsules. Because of its excellent flow, ANHYDROUS EMCOMPRESS is an ideal flow enhancer for capsule fillings. Monoclinic crystal habit EMCOMPRESS Triclinic crystal habit ANHYDROUS EMCOMPRESS

Differences Between EMCOMPRESS and ANHYDROUS EMCOMPRESS

Particle Size
Both materials have a median particle size ranging from 130 m to 150 m. As illustrated by the SEMS, both materials exhibit excellent crystallinity.

B
C B A

Fig. 4:

Magnification: 200x SEM of EMCOMPRESS

Fig. 5:

Magnification: 200x SEM of ANHYDROUS EMCOMPRESS

Fig. 7:

Binding Properties
EMCOMPRESS is denser, while ANHYDROUS EMCOMPRESS possesses a higher specific surface area. As a result, ANHYDROUS EMCOMPRESS produces harder compacts at equivalent forces. Tensile Strength as a Function of Compaction force
2.5

Literature about EMCOMPRESS :

Schmidt, P .C., Herzog, R., Pharm.World Sci. 15 (3), 105 and 116 (1993) Carstensen, J.T., Ertell,C. Drug Dev. Ind.Pharm. 16 (7), 1121 (1990)

ANHYDROUS EMCOMPRESS EMCOMPRESS

2.0

Tensile Strength (MPA)

1.5

Incompatibilities :
Calciumhydrogenphosphate is incompatible with tetra-cycline antibiotics and indomethacin. Due to its alkaline nature Calciumhydrogenphosphate should also not be used with active ingredients that are sensitive to a pH of 7.3 or above.

1.0

0.5

2.5

5.0

7.5

10

12.5

15

17.5

20.0

Compaction Force (kN) Fig. 6: Compaction force vs. tensile strength. Formulation: (99 % Calciumhydrogenphosphate + 1 % Magnesium Stearate). As can be seen, ANHYDROUS EMCOMPRESS is slightly more compressible than EMCOMPRESS

Disclaimer: The information provided in this brochure is based on thorough research and is believed to be completely reliable. Application suggestions are given to assist our customers, but are for guidance only. Circumstances in which our material is used vary and are beyond our control. Therefore, we cannot assume any responsibility for risks or liabilities, which may result from the use of this technical advice.

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