Easy Tableting with Natural Disintegrants

Evaluation of a new disintegrant mixture from natural resources

Introduction

Tablet disintegration is most often required to divide a tablet into suitably small sub-units that facilitate achievement of the desired drug dissolution rate. While semi-synthetic or synthetic super-disintegrants are commonly the materials of choice in the pharmaceutical world, there is a strong demand for options of more natural origin for nutraceutical applications.

Currently only few natural disintegrants are available and these sometimes do not achieve optimum disintegration due to lack of disintegrant action. To provide satisfactory disintegrant action one or more disintegration mechanisms can be facilitated. Swelling and wicking are usually considered the main drivers in tablet disintegration while strain recovery, dissolution mechanisms and the addition of surfactants are also reported to provide some disintegrative action.

Enabling synergistic effects of materials assisting swelling and wicking effects a mixture of natural materials (containing gellan gum, potato fiber, cellulose powder and natural potato starch) was optimized regarding the disintegration of various tablet formulations. The work presented here shows the disintegrant effect of this natural disintegrant mixture (CompactCel? DIS) in comparison to the disintegrant effect of a selection of natural disintegrant materials on their own (two types of starch and two types of cellulose).

Materials

All materials were used as supplied by the manufacturers without further conditioning. Materials were obtained from: Porous tribasic calcium phosphate (TCP 500) and a DC grade anhydrous dibasic calcium phosphate (DCPA 150), DC grade microcrystalline cellulose (MCC 200); Magnesiumstearate (Mg-St); ?affeine (Caff); coarse crystalline saccharose (Sacc); gellan gum; potato fibre as well as cellulose powder with a D50 of 70μm (CP_2) /; cellulose fine powder with a D50 of 30 μm (CP_1); native potato starch; pregelatinized corn starch. (all manufacturers are mentioned by name on the poster).

Methods

Powder Characterization

The materials were characterized regarding their particle size distribution (not shown here) water uptake speed (WUS), water uptake (WU) and swelling capacity (SC) using the setup comprising a glass vessel with a glass-sinter bottom as shown in Figure 1.

The apparatus was prepared by pumping water until the glass sinter was wetted evenly. A powder sample of an average mass of 5.0 g was inserted into the vessel on top of the glass sinter followed by slight manual levelling and compression to obtain an even powder bed. The connection to the water supply was opened and data recording started simultaneously. The height of the wetted and swollen powder bed was determined as well as the height of the unwetted powder bed after a run time of 30 min. The swell capacity was calculated from the volume of the actually wetted dry powder and the volume of the swollen wet powder.

The Diffusion Coefficient was determined by measuring the water penetration over time into a powder bed filled into 6 mm glass tubes and calculation with the simplified Washburn Equation (Figure 2 and Equation 2).

Tablet Formulations and Tablet Testing

Tableting mixtures were prepared by mixing the components as shown in Table 1 in a Turbula blender for five minutes (without Mg-St) and a further three minutes after addition of Mg-St. Mixtures were compressed on a RoTab T rotary press using flat-faced 11.28-mm punches. For F1 the main compression force (MCF) was 18.5 kN. Tablets were tested regarding their breaking force, dimensions and mass on a P5 tablet testing system (Charles Ischi AG). Disintegration was measured using an apparatus with integrated end-point determination DISI-EVO ( CHARLES ISCHI AG - OSD Testing Technology ).

Results

Figures 3 and 4 show the results of the water uptake and swelling tests. The water uptake capacity and the swelling capacity of the new disintegrant mixture is significantly higher than that of the cellulose and starch materials. In contrast to that the rate of water uptake is much faster for cellulose powders than for starches or the new CompactCel? DIS mixture. It can be observed that smaller cellulose particles effect a faster uptake. Comparing native potato starch with pregelatinized corn starch, it can be observed that the processed starch shows only very slow water uptake. Disintegration times for F1 (Figure 5) seem to be generally faster than those for F2 (Figure 6) while cellulose powders seem to show little disintegration action for F1. Starches show a good disintegration effect for F1 but not for F2. CompactCel? DIS shows a good disintegration effect in both formulations.

Conclusion

Tablet disintegration depends heavily on the tablet ingredients and the porosity of the compacts. The two examples above show that a fast uptake of water is not of paramount importance to achieve fast tablet disintegration. A high water uptake and swelling capacity is shown to be leading to faster disintegration in the given examples. The new CompactCel? DIS is an alternative disintegrant comprising only natural materials.

Download the contents of this article as poster here: https://mcusercontent.com/012b83f4e2c3f2c28a6c46697/files/c559f7c0-f5e2-95c9-b527-b74111197713/BIOGRUND_._CompactCel_DIS_._202403.pdf

This scientific poster was published at the PBP Worldmeeting / ResearchPharm? in Vienna (AT), March 2024.