Evaluation of Binders in Twin-Screw Wet Granulation

The binders povidone (Kollidon 30), copovidone (Kollidon VA64), hypromellose (Pharmacoat 606), and three types of hyprolose (HPC SSL‑SFP, HPC SSL, and HPC SL‑FP) were evaluated regarding their suitability in twin-screw wet granulation. Six mixtures of lactose and binder as well as lactose without binder were twin-screw granulated with demineralized water at different barrel fill levels and subsequently tableted.

A screening run with HPC SSL determined the amount of water as an influential parameter for oversized agglomerates. Subsequent examination of different binders, especially Kollidon 30 and Kollidon VA64 resulted in large granules. All binders, except Pharmacoat 606, led to a reduction of fines compared to granulation without a binder. The molecular weight of applied hyproloses did not appear as influential. Tableting required an upstream sieving step to remove overlarge granules. Tableting was possible for all formulations at sufficient compression pressure.

Most binders resulted in comparable tensile strengths, while Pharmacoat 606 led to lower and lactose without a binder to the lowest tensile strength. Tablets without a binder disintegrated easily, whereas binder containing tablets of sufficient tensile strength often nearly failed or failed the disintegration test. Especially tablets containing Pharmacoat 606 and HPC SL‑FP disintegrated too slowly.

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Article information: Köster, C.; Pohl, S.; Kleinebudde, P. Evaluation of Binders in Twin-Screw Wet Granulation. Pharmaceutics 2021, 13, 241. https://doi.org/10.3390/pharmaceutics13020241

Materials
Table 1 gives an overview of used binders. Different types of hyprolose were used. Table 2 lists their molecular weight and particle size. Additional applied substances were lactose monohydrate (Granulac® 200, Meggle, Wasserburg am Inn, Germany) as filler, silicium dioxide (Aerosil® 200 Pharma, Evonik, Hanau-Wolfgang, Germany) to improve flow properties, and magnesium stearate (LIGAMED® MF-2-V, Peter Greven Nederland C.V., Venlo, The Netherlands) as a lubricant for tableting

Conclusions
Granule and, therefore, tablet properties are influenced by different conditions. Consequently, examination at different process settings is necessary to draw a conclusion about the general influences of different types of binders. The present study examined six different binders as well as the absence of binders in the context of twin-screw wet granulation and subsequent tableting. An increase of L/S led to particle growth. The influence of SFL was not that obvious. Only in some cases, a higher SFL resulted in larger granules, albeit the influence might be opposed in binderless granulation. Granulation of pure lactose was possible and resulted in acceptable granules and tablets when high pressures were applied during tableting. Binders often reduced fines. However, granulation with Pharmacoat 606 resulted in a fraction of fines comparable to or even higher than binderless granulation. Kollidon 30 and Kollidon VA64 led to larger granules than other binders. Examining different HPC types, a clear influence of molecular weight or powder particle size was not verifiable.

Oversized granules, which were received with every binder but also without binder, were problematic for tableting and required a sieving step to ensure consistent tablet weights. Tablets of all compositions could be manufactured and exhibited sufficient tensile strengths above 200 MPa (binder containing tablets) or 240 MPa (binderless tablets) pressure application. Pharmacoat 606 tablets stood out by lower tensile strengths than other binder containing tablets but higher tensile strengths than binderless tablets. Disintegration was stated to be a problem when a binder was used. The addition of a disintegrant might ensure faster disintegration. Imagining continuous manufacturing processes, it is necessary to find granulation conditions, which inhibit the formation of oversized granules or integrate a continuous sieving step between granulation and tableting. However, the results of this study might not be transferable to less soluble powder compositions where the influence of the binder might be more important. Therefore, more investigations on different materials are required. Moreover, the usage of further twin-screw granulators seems to be vital and interesting for a better distinction of the suitability of different binders for twin-screw granulation.