Binder evaluation in tableting

A Genovesi^a, A Spadoni^a, C Funaro^a, and C Vecchio^b from IMA evaluate the binder introduction method on the granulation and tablet characteristics using Ghibli fluidised bed equipment

The purpose of granulation is primarily to improve the flow properties of the powder mixture and to improve its compression properties. The rate of granule formation depends on the amount of granulating liquid, which shows the maximum effect when the pores in the powder bed are filled with liquid.^1,2To form granules, bonds must be formed between powder particles so that they adhere with sufficient strength. Granulating agents, which aid drug and excipient aggregation, are a function of the binder type, the physical properties of the drug and the processing method.

binding methods

They are normally added as aqueous solutions or dispersions; alternatively, they can be mixed with other dry ingredients and water is added to the mixture. Different methods of binding the powder particles should produce different granulation results, and the aim of this work was to evaluate the two methods of binder introduction on:

the physical properties of the granules;

the tableting performance;

the physical characteristics of the tablets.

The starting excipient materials comprised a mixture of fine-crystalline lactose and corn starch, in a 4:1 ratio.

The binders tested were

polyvinylpyrrolidone (povidone, PVP; Kollidon K25, BASF)

hydroxypropylmethylcellulose (HPMC, Pharmacoat 606, Shin-Etsu)

and hydroxypropylcellulose (HPC, Klucel LF, Aqualon)

In the first experiment, water was used as the granulating liquid and the binder was added as a solid with the other materials. In the second experiment, a binder solution was added at a volume corresponding to the same amount of water used in the first trial.

The equipment used was a Ghibli model 003 fluidised bed granulation processor. The process parameters are shown in table 2.

Granulation was evaluated for particle size distribution, granule shape, flow properties, friability, bulk density, tapped density and moisture content. Tablets obtained by compression of the granulates were lubricated with 0.5% magnesium stearate using a single-punch press (IMA, Kilian SP 300), and were tested for average weight/weight variation, hardness, friability, thickness, and disintegration time according to the Ph.Eur. procedures.

liquid bridges

The agglomeration of powder particles is completely different when only water is used as a binding liquid compared with the adhesive polymer solution. This suggests a different binding mechanism. We would surmise that by adding water only, liquid bridges are formed between the particles - this is the initial condition for wet agglomeration - but, after the water evaporates, solid bridges are formed from the hardening binder and/or by recrystallisation of dissolved substances from the water, which have interacted with the binder.

Investigation of the granule size growth as a function of the binder using only water or the relevant binder solution may be a useful approach for determining the suitability of the binder as the starting materials.

Since the adhesive properties of binders depend on their interaction with the powders to agglomerate, the amount of the water used can be significantly different to achieve the right wetting state to reach correct agglomeration. Thus, it was necessary to use a different amount of water for each binder. Using PVP, the volume of water in the starting materials was 19.05% w/w, while larger volumes were used with HPMC (30.95% w/w) and HPC (39.52% w/w).

The addition of binder as a dry powder and water as the granulation liquid in the starting materials brought about the formation of granules of smaller particle sizes, but which were heavier and less free-flowing (Table 3 and figures 1-3).

performance properties

The tableting process of all granular products was performed without incurring particular compression problems. The tablets produced showed properties depending on the granule structure as a function of both the type of polymer and its method of introduction. Tablets prepared using PVP were softer than those using HPMC and HPC, and disintegrated in a shorter time independently of the binder addition method, table 1.

A balance between the resistance properties and the disintegration performance of the tablets would be a good compromise for defining a quality product. The use of IMA's Ghibli fluidised bed showed that fine granulations with good compression performance could be achieved by using both binder introduction methods: as a solution or with product in the dry form and wetting with water only.

All the results were good and the equipment guaranteed good performance reproducibility and final product quality.