Lactose

MorphologyThe morphology of spray-dried lactose is shown in the micrograph. The typical spherical granules consist of finely milled α-lactose monohydrate in a matrix of amorphous lactose. The spherical shape and narrow particle size distribution confer the excellent flow properties of spray-dried lactose. The amorphous lactose content and the small individual crystals within the granule are important in conferring the good compaction properties of spray-dried lactose.

Application notes

Spray-dried lactose

SuperTab® and Lactopress® are DFE Pharma’s brand names for direct compres sion lactose. Both SuperTab® 11SD and 14SD are made in a dedicated pharmaceutical lactose plant in Nörten-Hardenberg, Germany, and SuperTab® 11SD is additionally made in Kapuni, New Zealand. Lactopress® Spray Dried products are all made in Borculo, the Netherlands. SuperTab® and Lactopress® Spray Dried products comply with the requirements of the Ph. Eur., USP-NF and JP for lactose monohydrate. In the USP-NF they fall into the category of lactose monohydrate “modified”.

Comparative compactionSuperTab® 14SD is designed to have better compaction properties than for example SuperTab® 11SD and Lactopress® Spray Dried 250. This is a result of the optimisation of both the particle size of the crystalline component and the level of amorphous lactose. The improvement in tablet strength may be useful for formulations that require extra compactability or the lower compaction forces required to achieve a given tablet strength can result in reduced tooling wear. (250 mg tablets / 9 mm flat bevel tooling: 0.5% mag stearate)

Compaction Force (kN)

Tab

let S

tren

ght (

N) 200

125

175

100

150

75

508 10 12 14 16

SuperTab® 14SD SuperTab® 11SD Lactopress® Spray Dried 250

DFE Pharma direct compression products

Product type Product name Product attributes and applications

Spray-dried lactose Lactopress® Spray Dried Direct Compression

Lactopress® Spray Dried 250 Direct Compression

Lactopress® Spray Dried 260 Direct Compression, for further improved flowability

SuperTab® 11SD Direct Compression

SuperTab® 14SD Direct Compression, high compactability

Granulated lactose Lactopress® Granulated Direct Compression, good all round performance

SuperTab® 30GR Direct Compression, good all round performance

Anhydrous lactose Lactopress® Anhydrous Direct Compression

Lactopress® Anhydrous 250 Direct Compression, dry granulation, encapsulation

SuperTab® 21AN Direct Compression, dry granulation, encapsulation

SuperTab® 22AN Direct Compression, free flowing grade

Head OfficeKlever Strasse 187P.O. Box 20 21 2047568 Goch, GermanyT. +49 2823 9288 770F. +49 2823 9288 7799pharma@dfepharma.com

DMV-Fonterra Excipients GmbH & Co. KG - WarrantyThe details given here are merely intended for information purposes and are in no way legally binding. Consequently we accept no responsibility in the broadest sense of the word for damage that may result from applications based upon this information. Furthermore, this information does not constitute permission to infringe patent and licence rights.

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Direct compressionSpray-dried lactose is an excellent choice for direct compression formulations. At its simplest the formulation need only contain the API, spray-dried lactose, a superdisintegrant and a lubricant. Excellent content uniformity of low dose tablets is achieved by employing a mixing scheme that effectively de-agglomerates the API. This can be achieved by the preparation of a premix which is subjected to a de-agglo merating step (such as sieving through a 500 μm screen or use of an intensifier bar in a V-blender) before completion of mixing.

The effectiveness of such a mixing scheme can be seen in the example below using milled paracetamol (NAPA) as a model API at levels of 0.5 mg and 5 mg in 250 mg tablets. In the first example (left) the overall RSD through the tableting run was 2.3% with a single tablet range of 93% to 105%. The corresponding data for the second example (right) were RSD of 1.6% and range 98% to 105%.

Selection of superdisintegrantBoth Primojel® (sodium starch glycolate) and Primellose® (croscarmellose sodium) are suitable disintegrants for Lactopress® Spray Dried or SuperTab® SD, used at starting levels of 2% to 4% in a typical direct compression formulation. Physical stability of tablets using these combinations is also good.

Slight hardening of the tablets may be expected on storage (attributed to crystallisation of the amorphous lactose) and disintegration time tends to decrease slightly with Primellose®. The data below were generated after 6 months storage at 40˚C / 75% RH in open containers. Under these conditions the tablets did not increase in thickness or weight.

Tableting duration (min)

Sin

gle

tab

let a

ssay

(mg) 0,575

0,500

0,550

0,475

0,525

0,450

0,4250 5 10 15 20 25 30

SuperTab® 11SD / 0,5 mg NAPA Tableting duration (min)

Sin

gle

tab

let a

ssay

(mg) 5,75

5,00

5,50

4,75

5,25

4,50

4,250 10 20 30 35

SuperTab® 11SD / 5 mg NAPA25155

Time (months)

Tab

let s

tren

gth

(N) 250

200

150

50

00 1 2 3 4 5 6

100

2% Primojel® 4% Primojel® 2% Primellose® 4% Primellose®

Time (months)

Dis

inte

grat

ion

tim

e (m

in) 10

6

4

8

2

00 2 4 6531

2% Primojel® 4% Primojel® 2% Primellose® 4% Primellose®

Premix API with about 20% of the SD-lactose

De-agglomerate (500 μm screen or intensive mixing)

Blend with remaining excipients

Lubricate & compress