LYCOAT® RS 780 modified pea starch as efficient binder for wet granulation

Introduction

Pregelatinized hydroxypropyl pea starch is known for its good film forming1 and quick hydration2 properties. Its qualities thus make it a good candidate as wet granulation binder to be used in both wet and dry form.

Experimental strategy

In this study, a mannitol/starch blend was granulated using either PolyVinylPyrrolidone (PVP) or pregelatinized hydroxypropyl pea starch (RS780) as binders. PVP and LYCOAT® RS780 powders were introduced in dry form or in solution in the mannitol/starch blend. Granules’ characteristics as well as the tablets’ properties made from them were measured. 

Materials and methods

Materials

PEARLITOL® 50 C, crystalline mannitol powder (Roquette Frères, France)Extra white maize starch (Roquette Frères, France)
LYCOAT® RS 780, pregelatinized hydroxypropyl pea starch (Roquette Frères, France)   
Kollidon® 30, povidone K30 (PVP) (BASF, Germany) 
Vegetal magnesium stearate 

Granulation trials 

1500 g of mannitol (77.6%) and maize starch (19.4%) were granulated in a high shear mixer Diosna® P1-6 (Diosna, Germany) (impeller at 250 rpm and chopper at 1800 rpm) with 300 g of sprayed water. The binder (3%), Kollidon® 30 or LYCOAT® RS 780 were added either in the dry phase or dissolved in the wetting solution.
Obtained granules were dried in a Aeromatic Strea-1TM (Aeromatic, UK) at 50°C and calibrated with an Erweka® oscillating rotor (1000 µm) (Erweka, Germany).

Tableting trials 

600 g of granules (99.5%) and magnesium stearate (0.5%) were mixed in a Turbula mixer for 5 minutes. Tablets were made with Stylcam 200R (Medelpharm, France) press simulator equipped with D10R10 concave punches at 40 rpm and 5 compression forces (5, 10, 15, 20, 25 kN). The compression speed studied here (40 rpm) simulates industrial rotary press production rate corresponding to about 240,000 tablets per hour.

Tablets’ evaluation

Weight, thickness, diameter and hardness were evaluated with a Pharmatron® ST50 (Sotax AG, Switzerland).
Disintegration time was measured with a Pharmatron® DT50 (Sotax AG, Switzerland).
Friability was evaluated with a friability tester TAR 220 (Erweka Gmbh, Germany).

Results 

PVP is considered to provide excellent binding strength and was taken as reference in this study. 
Powders’ properties after granulation were evaluated.

 

According to the physical characteristics shown in table 1, all granules were considered to be suitable for being tableted. Granules made with 3% PVP in dry form show lower values regarding moisture content and densities compared to the other three trials. Granulation time being the same for all formula, this difference may be due to the lower hydration capacity of PVP.

 

Figure 1. Impact of the binder addition method on the granules’ tabletability.

 

Figure 1 shows that tablets made with LYCOAT® RS 780 granulated powder exhibit the same hardness whether the binder is incorporated in dry or liquid form. The maximum hardnesses reached are 93 and 102 N at 25 kN compression force respectively for liquid and dry addition. For LYCOAT® RS 780, no tablet defect is observed, whatever the binder incorporation mode. 
Granules bound with PVP show a lower tabletability than those made with LYCOAT® RS 780 with a maximum hardness reached of 88 N at 25 kN. Granulation with PVP in dry form leads to capping at 20 kN, probably due to an incomplete hydration and heterogeneous distribution.

 

Figure 2. Impact of the binder type and incorporation mode on tablet friability.

 

Figure 2 shows that an acceptable tablet friability is reached as soon as the tablets hardness is close to or exceeds 40 N for all the trials except for the granules produced with the PVP in dry form. For this particular formula, tablets made at 15 kN (having a hardness of 58 N) have internal defect highlighted here by a high friability value).

 

Figure 3. Ejection forces resulting from tableting. 

 

Figure 3 shows that tablets made with both dry and solubilized PVP generate high ejection forces compared to those generated by the granules that include LYCOAT® RS 780. These high ejection forces may indicate the presence of fine particles due to a lower binding efficiency during the granulation. 

 

Figure 4. Impact of the binder on disintegration time.

 

Figure 4 shows that all the formulations allow to make tablets with a high disintegration speed. Nevertheless, some differences can be observed as the disintegration times of tablets made with PVP are longer than those of tablets made with LYCOAT® RS 780.

Conclusion

This study shows that LYCOAT® RS 780 has good binder properties: it leads to hard, low friability, low ejection force and short disintegration time tablets.  In addition, LYCOAT® RS 780 presents a high versatility since it may be used indifferently in dry or liquid form. Similar granules characteristics and tablet properties obtained whatever the incorporation mode is due to its quick hydration kinetics.2 
In the same conditions, PVP provides lower tablet properties. In addition, PVP seems to need longer hydration time, making it more difficult to be incorporated in dry form.

References

1. https://fr.roquette.com/-/media/contenus-gbu/pharma/scientific-posters/roquette-pharma-case-study-novel-modified-starch-over-hpmc-in-aqueous-film-coating.pdf
2. Vandevivere, L., Vangampelaere, M, Portier, C., de Backere, C, Häusler, O., De Beer, Th., Vervaet, Ch., Vanhoorne, V., Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process, Pharmaceutics 2021, 13, 210. 

https://doi.org/10.3390/pharmaceutics13020210

 

Kollidon® 30 is a registered trademark of BASF, Germany. 
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Disclaimer

The information contained in this document is to the best of our knowledge true and accurate, but all instructions, recommendations or suggestions are made without guarantee. Since the conditions of use are beyond our control, we disclaim any liability for loss and/or damage suffered from use of these data or suggestions. Furthermore, no liability is accepted if use of any product in accordance with these data or suggestions infringes any patent. No part of this document may be reproduced by any process without our prior written permission