Evaluation of binders in twin-screw wet granulation - Optimization of tabletability.

The influence of hydroxypropyl cellulose type (HPC-SSL SFP, HPC-SSL), concentration (2 %, 3.5 %, 5 %) and filler (lactose, calcium hydrogen phosphate (DCP)/microcrystalline cellulose (MCC)) on twin-screw wet granulation and subsequent tableting was studied. The aim was to identify the formulation of the highest tabletability which still fulfills the requirements of the disintegration. Lactose combined with 5 % binder enabled a higher tabletability and a faster disintegration than DCP/MCC. It was found that tabletability of lactose formulations can be increased by higher binder concentration and higher compression pressure while tabletability of DCP/MCC formulations can be only increased by higher compression pressure. It was observed that batches containing DCP/MCC failed the disintegration test, if the highest binder concentration and the highest compression pressure were used. To ensure a fast disintegration, the compression pressure or at least the binder concentration had to be low. Changing the disintegrant and its localization improved the DCP/MCC formulation, resulting in faster disintegration than lactose tablets. However, it also resulted in a lower tabletability. In this study best tablets were achieved with 3.5 % or 5 % binder and lactose as filler. These tablets presented the highest tabletability but still disintegrated in less than 500 s.

Evaluation of binders in twin-screw wet granulation - Optimal combination of binder and disintegrant.

The influence of localization (intragranular, split or extragranular) of three superdisintegrants (croscarmellose sodium, crospovidone, sodium starch glycolate) on granules and tablets after twin-screw granulation was studied. The aim was to find a suitable disintegrant type and disintegrant localization for lactose tablets manufactured with different hydroxypropyl cellulose (HPC) types. The disintegrants were found to decrease the particle size in granulation, where sodium starch glycolate had the lowest influence. The tablet tensile strength was not influenced strongly by the disintegrant type or localization. By contrast, the disintegration was dependent on the disintegrant type as well as the localization, where sodium starch glycolate performed worst. Intragranular croscarmellose sodium and extragranular crospovidone were identified as beneficial for chosen conditions because a satisfying tensile strength in combination with the fastest disintegration was found. These findings were achieved for one HPC type and the suitability of the best disintegrant-localization-combinations was confirmed for another two HPC types.

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 SSL­SFP, HPC SSL, and HPC SL­FP) 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 SL­FP disintegrated too slowly.