Evaluation of Binders in Twin-Screw Wet Granulation

Abstract

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.

Co-Spray Drying of Paracetamol and Propyphenazone with Polymeric Binders for Enabling Compaction and Stability Improvement in a Combination Tablet

“…Comparing the PCT-hpc15/PRP and PRP-hpmc10/PCT tablets, the former showed greater toughness (1.53 compared to 0.66 mJ) and tensile strength (2.93 MPa compared to 2.23 MPa). The greater toughness and strength of PCT-hpc15/PRP are partly due to the higher polymer content (15% vs. 10%) and partly due to the higher strength of HPC bonds [ 36 ]. The slopes of the curves of the green tablets in the initial linear elastic region (up to 0.4 mm displacement) appear similar for the three drug mixture tablets with physical mixture having lower elastic modulus (258.6 MPa) followed by PCThpc15/PRP (268.3 MPa) and PRP-hpmc10/PCT (295 MPa).…”

Advances in Twin-Screw Granulation

“…However, this could not be generalized, as it was observed that by inclusion of, for example, hydroxypropyl methylcellulose (HPMC) E15 in the formulation, higher friabilities were observed compared to pure mannitol granules. Similarly, Köster et al [5] demonstrated that inclusion of HPMC Pharmacoat 606 resulted in more fines in the lactose-based formulation compared to pure lactose granules. Furthermore, both studies highlighted a negative impact of binders on disintegration times, with some binders resulting in unacceptably long disintegration times [4,5].…”

“…Similarly, Köster et al [5] demonstrated that inclusion of HPMC Pharmacoat 606 resulted in more fines in the lactose-based formulation compared to pure lactose granules. Furthermore, both studies highlighted a negative impact of binders on disintegration times, with some binders resulting in unacceptably long disintegration times [4,5]. Nevertheless, disintegrants were hypothesized to be able to compensate for the delay in disintegration due to the inclusion of a binder.…”

“…Whereas the use of surfactants in formulations is not uncommon, binders are routinely added to formulations to favor the production of high-quality granules and tablets. Therefore, binder selection for TSG was addressed in two research papers [4,5]. As the residence time in the process is much shorter compared to batch-wise wet granulation processes, it was anticipated that critical binder characteristics could differ between continuous and batch-wise granulation techniques.…”

“…In both studies, binary filler/binder mixtures were granulated in a filler/binder ratio of 95/5, and the binders were included in the powder mixture prior to granulation. Whereas Köster et al [5] focused on the combined impact of binders and the specific feed load on granule size distributions and final tablet properties of a lactose-based formulation, Vandevivere et al [4] focused on the critical binder attributes impacting the granule friability of both a mannitol-and dicalciumphosphate (DCP)-based formulation. The wettability of binder particles by water, as well as the wettability of surfaces by binder solutions and the low surface tension of binder solutions, proved crucial for both mannitol-based and DCP-based formulations.…”