Mechanical properties of tablets: direct compression vs. twin-screw melt granulation with PEG 8000

This poster was presented at the DDF Summit Conference 2024 by Valentyn MOHYLYUK, Zoltán Márk HORVÁTH, Kirils KUKULS, Liga LAUBERTE, Artūrs PAULAUSKS from Rīga Stradiņš University:

Introduction

• Replacing batch wet granulation with twin-screw melt extruder as a continuous solventless process is gaining popularity. PEG 8000 being one of the most popular excipients used for melt granulation lacks thorough investigation regarding its effect on the mechanical properties of tablets. Along with PEG 8000, a mixture of microcrystalline cellulose (MCC) and calcium phosphate anhydrous (CaHPO4) was chosen for granulation due to its unsatisfactory flowability.
• This study aimed to investigate the effect of PEG 8000 particle size and twin-screw melt granulation temperature on the properties of resultant MCC-CaHPO4 granules and their tablets
• and to compare tablet mechanical properties of ungranulated (DC) and melt-granulated MCC-CaHPO4

Materials

• MCC – CEOLUS UF-711 (Asahi Kasei, Japan); CaHPO4 – DI-CAFOS A60 (Budenheim KG, Germany); PEG 8000 – Kollisolv® (BASF SE, Germany)
• Silica dioxide – SYLOID® 244FP (Grace GmbH, Germany) and Sodium stearyl fumarate – PRUV® (JRS Pharma, Germany) were used for directly compressed tablets (DC) where PEG 8000 was not used [1-2].

Methods [1-2]

• Twin-Screw Melt Granulation was carried out using a Pharma 11 Extruder without nozzle, a Volumetric Mini Feeder, and a Conveyor (Thermo Electron Corp., Germany). The part of barrel that was used had a flighted length of 259mm and a diameter of 11mm with a length/diameter ratio (L/D) of 23.5:1. The screw design consisted of 1 L/D feed screw elements
• Ungranulated (incl. SYLOID® 244FP and PRUV®; without PEG 8000) [1] and melt granulated (Table 1 [2]) tablets (D 11.28mm; flat punches; 500 mg) were prepared using a compaction simulator (Styl’One Nano, MEDELPHARM, France) simulating small rotary tablet press at 70 rpm; 50 MPa pre-compaction pressure and 100-250 MPa compaction pressure.
• The tablet thickness, diameter, and hardness, were measured (n=10) by a tablet tester (ST50 WTDH, SOTAX AG, Switzerland) immediately after the compaction and converted into tensile strength (MPa).
• The calculated true density of composition was obtained on the true density (ρt) of components and their shares (x, w/w): 𝜌𝑡 = (𝜌1 ∙ 𝑥1 ) + (𝜌 2 ∙ 𝑥2 ) + ⋯ + (𝜌 𝑖 ∙ 𝑥𝑖 )
• For in-die Heckel plot, the relative density ln(1/ε) was calculated with Alix software (MEDELPHARM). The relative density and compaction pressure were plotted in accordance with the Heckel eq.:
  • 𝑙𝑛(1⁄𝜀) = MPa𝐾 ∙ 𝑃 + 𝑙𝑛(1⁄𝜀0 ) =𝐾∙𝑃 + 𝐴
• Scanning Electron (TM4000 Plus, Hitachi, Japan) and optical (BA410E, Motic, China) microscopy were used

Results

• The size of granules increased with increasing PEG 8000 particle size and granulation temperature
• Optical microscopy of tablets revealed the individual granules and their points of contact (Fig. 2)
• Raman mapping confirmed the location of components and their conformation according to the optical microscope images in Fig. 2.
• The plasticity of formulations increased with decreasing PEG 8000 particle size and with decreasing granulation
  temperature (Fig. 3).
• The elastic energy of formulations increased with increasing PEG 8000 particle size and granulation temperature (Fig. 4).
• Tabletability decreased with increasing PEG 8000 particle size and with increasing granulation temperature (Fig. 5).
• Tabletability of ungranulated material was higher than that of melt granulated.

Conclusion

• PEG 8000 particle size and granulation T℃ influenced the granule’s properties
• Structure of granules influenced tablet structure (Fig. 2) & formulation plasticity (Fig. 3)
• Structure of granules, their plasticity, and structure of tablets influenced their mechanical properties (Fig. 3-5).
• Most plastic melt granulated formulations showed best tabletability (Fig. 3, 5).
• Melt-granulated formulations showed lower tensile strength compared to ungranulated directly compressed tablets (Fig. 5).

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Source: Valentyn MOHYLYUK, Zoltán Márk HORVÁTH, Kirils KUKULS, Liga LAUBERTE, Artūrs PAULAUSKS, Mechanical properties of tablets: direct compression vs. twin-screw melt granulation with PEG 8000, DDF Summit poster “Mechanical properties of tablets”