@conference{
author = "Aleksić, Ivana and Ćirin-Varađan, Slobodanka and Glišić, Teodora and Đuriš, Mihal and Đuriš, Jelena and Parojčić, Jelena",
year = "2022",
abstract = "1. INTRODUCTION
Co-processing has emerged as a suitable
approach to meet the increasing demands for
excipients with improved tableting
performance. Apart from the most commonly
used energy-consuming co-processing methods
(e.g. spray-drying and wet granulation), melt
granulation as a solvent-free and more
environmentally friendly technique has recently
gained more attention [1].
The aim of the present study was to investigate
the influence of meltable binder particle size
and compaction parameters on dilution capacity
and compaction behaviour of lactose-based coprocessed
excipients.
2. MATERIALS AND METHODS
2.1. Materials
Paracetamol (Acros Organics, Belgium) was
used as the model drug. Lactose monohydrate
(Carlo Erba Reagents, Italy) was used as filler
and glyceryl palmitostearate (Precirol® ATO 5
Gattefossé S.A.S, France) as meltable binder.
2.2. Preparation of co-processed excipients
Co-processed excipients were prepared by in
situ melt granulation in Mycrolab fluid bed
processor (OYSTAR Hüttlin, Germany).
Precirol® particles (15%) from the 125–180 μm
(≈ 150 μm) or 600–710 μm sieve fraction (≈ 655
μm) were used for granulation of lactose (85%).
The inlet air flow rate was 30 m3/h, and product
temperature during agglomeration was 65 °C.
2.3. Particle size and shape analysis
Granule size distribution was evaluated by sieve
analysis, and median particle diameter (d50) was
calculated by linear interpolation of the
cumulative percentage frequency curve.
Granule shape was examined by 2D scanned
image (4800 dpi resolution) analysis using
ImageJ software. The aspect ratio (AR) and
circularity (C) were calculated for granule shape
evaluation.
2.3. Determination of the Carr index
The bulk and tapped (1250 taps) densities of coprocessed
excipients and their mixtures with 30,
40 or 50% paracetamol were determined using
tap density tester STAV 2003 (J. Engelsmann
AG, Germany), and Carr index was calculated.
2.4. Dynamic compaction analysis
Co-processed excipients and their mixtures with
paracetamol were compressed on a single punch
instrumented tablet press (GTP D series,
Gamlen Tableting Ltd, UK). Compacts (100
mg) were compressed under compression load
of 200 kg (≈ 70 MPa) or 500 kg (≈ 173MPa),
and compression speed of 60 or 120 mm/min. 6
mm flat faced punches were used. The obtained
force-displacement curves were used to
calculate: net work of compression (NW),
detachment stress (DS), ejection stress (ES).
Tablet crushing force was determined using
tablet hardness tester Erweka TBH 125D
(Erweka GmbH, Germany), and the values
obtained were used to calculate tensile strength
(TS). Elastic recovery (24 h after compression)
was calculated, as well.
2.4. Experimental Design
In order to investigate the influence of binder
particle size, paracetamol content and
compression speed on the abovementioned
compaction properties, compacts were
prepared, at compression load of 500 kg,
according to 23 full factorial design.
3. RESULTS AND DISCUSSION
3.1. Particle size and shape
Larger initial binder particle size led to
formation of larger and more spherical granules
(Table 1).
147
Table 1. The size and shape of the co-processed
excipients’ particles.
Binder PS (μm) d50 AR C
150 564.9 1.33 0.81
655 846.2 1.14 0.86
3.2. Flowability
The Carr index values obtained indicated
considerably better flowability of the coprocessed
excipient prepared by using larger
binder particles (P655) in comparison with the
excipient prepared with smaller binder particles
(P150). This might be ascribed to more
spherical and larger particles of P655. However,
the addition of paracetamol led to an increase in
Carr index values and less pronounced
differences between two excipients (Fig. 1).
Figure 1. The influence of paracetamol loading
on flowability of co-processed excipients.
3.3. Compaction behaviour
The results obtained revealed better mechanical
properties of P150 in comparison with P655
compacts, irrespective of the compression
pressure applied. The addition of paracetamol,
as the model API with poor compaction
properties, led to decrease in tensile strength of
the compacts prepared with both excipients, and
paracetamol content showed statistically
significant influence on TS (p < 0.0001).
Acceptable tensile strength (> 1 MPa) could be
achieved for compacts with 30% paracetamol
compressed at higher compression pressure (≈
173 MPa).
Paracetamol content, compression speed and
interaction between binder particle size and
paracetamol content were found to significantly
affect NW. The influence of binder particle size
was more pronounced at higher paracetamol
content, with lower NW observed in the case of
P655. Higher compression speed led to higher
NW.
Relatively low values of detachment and
ejection stress (< 3.5 MPa) indicate good
antiadhesive and lubricating properties of the
investigated excipients. Lower values of both
parameters were observed in the case of P655
which could be related to different
agglomeration mechanisms involved. Besides
binder particle size, compression speed and
paracetamol content were found to significantly
influence these properties.
Elastic recovery values of the investigated
samples ranged between 12 and 28%. In the
case of both excipients, higher elastic recovery
values were obtained at higher compression
pressure. ER values of the compacts prepared at
higher compression pressure were significantly
affected by compression speed and interactions
of the investigated variables.
4. CONCLUSION
The results obtained show that meltable binder
particle size affects granule size and shape, and
consequently may influence flowability and
compaction behaviour of the co-processed
excipients. Interactions between binder particle
size and compaction variables were also found
to affect compaction properties of the
investigated excipients.",
publisher = "Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo",
journal = "9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts",
title = "Evaluation of dilution capacity and compaction behaviour of the excipients co-processed by in situ fluidized bed melt granulation",
pages = "146-147",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4735"
}
