A Closer Look At Primellose®

Primellose® is croscarmellose sodium USP-NF, a cross-linked carboxymethylcellulose sodium. Cross-linking reduces its water solubility and permits the material to swell and take up many times its weight in water without loosing its fibrous integrity.

Primellose® has been allosed in the U.S as a pharmaceutical ingredient under Registration Number of the Drug Master File 9662, submitted April 21, 1992.

Disintegration Mechanism

The excellent disintegration efficiency of croscarmellose sodium Primellose® is caused by the combination of rapid water penetration into tablets via the hydrophillic, fibrous disintegrant particles and the subsequent development of a disintegration force.

Drug Dissolution

Croscarmellose sodium Primellose® improves the drug dissolution rate from capsules and tablets prepared by direct compression or by wet granulation.

Application in tablets prepared by direct compression

Table 1: Oxazepam tablets 10 mg

Oxazepam	4.0 %
Spray dried lactose	45.4 %
alpha-Lactose monohydrate 100 Mesh	45.4 %
Primellose®	4.0 %
Colloidal silica	0.2 %
Magnesium stearate	1.0 %
Variation coefficient of tablet weight	0.95 %
Crushing strength	70 N
Disintegration time (without disks)	25 s

In tablest prepared by direct compression, the effective concentration of Primellose® is between 1 and 4%.

Table 2: Hydrochlorothiazide tablets 100 mg
* Two series of tablets were made with a different croscarmellose sodium:
- Primellose
- Product A (another croscarmellose sodium available on the market)

Hydrochlorothiazide	20.0 %
Dicalcium phosphate dihydrate	38.5 %
Anhydrous lactose	38.5 %
Croscarmellose sodium*	2.0 %
Mg Stearate	1.0 %

Table 1 shows an example for a tablet formulation of oxazepam tablets, prepared on an instrumented single punch tabletting machine at a compaction force of 20kN. Tablet diameter: 9mm. Tablet weight: 200mg.

Table 2 shows a formulation example for hydrochlorothiazide tablets, prepared with two different brands of croscarmellose sodium: Primellose® and Product A, another brand available on the market. Tablets of 500mg with a diameter of 13mm were prepared on a single punch machine at a compaction force giving a crushing strength of 60N.

The disintegration time measured according to the USP without disks was about 50 s for both kinds of tablets. The dissolution velocity, measured in 0.1 N HCl at 37° using the USP paddle method at 100 rpm is presented in figure 1.

Application in tablets prepared by wet granulation

In tablets prepared by wet granulation, the effective concentration lies between 2 and 4%. The disintegrant may be incorporated intragranularly, extra-granularly, or equally distributed.

Table 3 shows a formulation example for hydrochlorothiazide tablets, prepared by wet granulation. Granules were prepared by moistening a mixture of drug, filler and disintegrant in a planetary mixer with a 5% PVP solution. Tablets of 500mg with a diameter of 13mm were prepared on a single punch machine at a compaction force of 20kN.

The disintegration time measured according to the USP without disks was about 40 s for both kinds of tablets.