Content uploaded by Valentyn Mohylyuk
Author content
All content in this area was uploaded by Valentyn Mohylyuk on Mar 24, 2024
Content may be subject to copyright.
Twin-Screw Melt Granulation with PEG 8000:
effect of binder particle size and processing temperature
on the granule and tablet properties
Zoltán Márk Horváth, Liga Lauberte, and Valentyn Mohylyuk
Laboratory of Finished Dosage Forms, Faculty of Pharmacy, Rīga Stradiņš University, LV-1007 Riga, Latvia
Horváth Z.M, Liga L, Mohylyuk V. Twin-Screw Melt Granulation with PEG 8000: effect of binder particle size and processing temperature on the granule and tablet properties. 14th PBP World Meeting; Vienna, Austria, 2024.
Methods
•Twin-Screw Melt Granulation was carried out using a Pharma 11 Extruder
without nozzle, a Volumetric Mini Feeder, and a Conveyor (Thermo Electron
CorporationGermany). The part of barrel that was used had a flighted length of
259 mm and a diameter of 11 mm with a length/diameter ratio (L/D) of 23.5:1.
The screw design consisted of 1 L/D feed screw elements
•Tablets (Table 1; D 11.28 mm; 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 (t), diameter (d), and hardness (F), 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 = (𝜌𝑒𝑥𝑐 1 ∙ 𝑥𝑒𝑥𝑐 1 ) + (𝜌𝑒𝑥𝑐 2 ∙ 𝑥𝑒𝑥𝑐 2 ) + ⋯ + (𝜌𝑒𝑥𝑐 𝑖 ∙ 𝑥𝑒𝑥𝑐 𝑖 )
•For in-die Heckel plot, the relative density ln(1/ε) was calculated with Alix
software (Medelpharm). The relative density and compaction pressure (P,) data
were plotted in accordance with the Heckel equation:
𝑙𝑛(1⁄𝜀) = MPa𝐾 ∙ 𝑃 + 𝑙𝑛(1⁄𝜀0 ) = 𝐾 ∙ 𝑃 + 𝐴
•Optical (BA410E, Motic, China); Scanning Electron (TM4000 Plus, Hitachi,
Japan); Raman (VirsaTM, Reinshaw plc., UK) microscopy were used.
Introduction
•High-drug-loaded tablets and capsules are desirable and are manufactured using
granulation as an additional step. 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.
•The aim of this study was 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.
Discussion & Conclusion
•PEG 8000 particle size and granulation temperature influenced
the granule’s properties (Fig. 1, 5-9)
•Structure of granules influenced formulation plasticity (Fig. 5)
•Structure of granules, their plasticity, and structure of tablets
influenced their mechanical properties (Fig. 7-10).
•Most plastic formulations showed best tabletability profiles
(Fig. 6, 8).
•Melt-granulated formulations showed lower tensile strength
compared to ungranulated directly compressed tablets (Fig. 8).
Results
•The size of granules increased with increasing PEG 8000 particle size and granulation
temperature (Fig. 1)
•Optical microscopy of tablets revealed the individual granules and their points of contact (Fig. 2)
•Raman mapping (Fig. 3) confirmed the location of components and their conformation according
to the optical microscope images in Fig. 2.
•CaHPO4 particles are surrounded by PEG 8000 coated MCC particles within tablets (Fig. 4).
•The plasticity of formulations increased with decreasing PEG 8000 particle size and with
decreasing granulation temperature (Fig. 5).
•The plastic energy (Fig. 6) and tensile strength (Fig. 8) of formulations (up to 150 MPa)
decreased with increasing PEG 8000 particle size and with increasing granulation temperature.
•The elastic energy of formulations increased with increasing PEG 8000 particle size and
granulation temperature (Fig. 7).
•Compressibility decreased with increasing PEG 8000 particle size and with increasing
granulation temperature (Fig. 9).
Fig. 1
S135
M115
M135
M155
B135
Formulation
MCC (wt.%)
56
CaHPO
4 (wt.%) 34
PEG 8000
0
-200 µm (wt.%)
10
- - - -
200
-400 µm (wt.%) -
10
10
10
-
400
-500 µm (wt.%) - - - -
10
Processing parameters
Zone
1 (°C) 20
Zone 2 (
°C)
80
70
80
90
80
Zone 3 (
°C)
135
115
135
155
135
Zone
4 (°C)
135
115
135
155
135
Zone
5 (°C)
60
60
60
60
60
Feed rate (g/min)
1.582
Screw speed (rpm)
120
Torque (%)
2
Table 1
Fig. 5
Fig. 8
Fig. 9 Fig. 10
Fig. 6
Fig. 7
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 [ref.].
0-200 µm
115 ℃
135 ℃
155 ℃
200-400 µm
400-500 µm
Fig. 2
PEG 8000
Fig. 3 Fig. 4
135 ℃
intensity of:
(b) PEG 8000
(c) CaHPO4
(d) MCC
Ref.: Mohylyuk V, Paulausks A, Radzins O, Lauberte L. The Effect of Microcrystalline Cellulose–CaHPO4
Mixtures in Different Volume Ratios on the Compaction and Structural–Mechanical Properties of
Tablets. Pharmaceutics. 2024;16(3), 10.3390/pharmaceutics16030362.