@conference{
author = "Glišić, Teodora and German Ilić, Ilija and Parojčić, Jelena and Aleksić, Ivana",
year = "2022",
abstract = "1. INTRODUCTION
Maintaining good compaction properties of
liquisolid systems (LSS) is particularly
challenging in the case of high-dose drugs [1].
High amount of liquid phase within LSS,
required to dissolve/suspend higher amount of
drug substance, while necessary for
improvement of bioavailability, can cause
difficulties during the tableting process,
resulting in low tablet hardness or even inability
of admixtures to be directly compressed. This
has led to the development of new highly porous
carriers, specifically designed for LSS, that can
adsorb/absorb very high amount of liquid phase.
The aim of this study was to investigate the
compaction properties of LSS, prepared with
three types of novel silica-based mesoporous
carriers, using dynamic compaction analysis as
a tool, with the focus on compressibility,
compactibility and tabletability of these systems
[2].
2. MATERIALS AND METHODS
2.1. Materials
Amorphous magnesium aluminometasilicate
(Neusilin® US2, Fuji Chemical Industry Co,
Ltd., Japan) and two types of amorphous
mesoporous silicon dioxide (Syloid® XDP 3050
and Syloid® XDP 3150, Grace GmbH,
Germany) were used as carriers. Colloidal
silicon dioxide (Aerosil 200, Evonik Industries
AG, Germany) was used as coating material and
polyethylene glycol 400 (PEG 400, Fagron,
Netherlands) was used as liquid phase.
2.2. Liquisolid Admixture Preparation
LS admixtures (Table 1) were prepared using
Mycrolab fluid bed processor (OYSTAR
Hüttlin, Germany), with the operating
temperature of 30°C, inlet air flow rate of 20
m3/h, and liquid feed rate of 12 g/min.
Table 1. Composition of prepared LS
admixtures
Liquisolid
admixturesa Rb Liquid
load
PEG
400 (%)
S1 10 0.7 38.9
S2 30 0.7 40.4
S3 10 0.6 35.3
S4 30 0.6 36.7
N1 10 1.1 49.8
N2 30 1.2 54.7
a type of carrier used: S1, S2 - Syloid® XDP
3050, S3, S4 - Syloid® XDP 3150, N1, N2 -
Neusilin® US2; bcarrier to coating material ratio
2.3. Powder density
LS admixtures’ true densities were determined
by helium pycnometer (AccuPyc 1330,
Micromeritics, GA) while bulk and tapped
densities were measured using a graduated
cylinder and a volumeter (STAV 2003, J.
Engelsmann AG, Germany).
2.4. Powder morphology
The morphology of LS particles was examined
using a scanning electron microscope (SEM,
Supra 35VP, Carl Zeiss, Germany).
2.5. Dynamic compaction analysis
Dynamic compaction analysis was performed
on an instrumented tablet press (GTP D series,
Gamlen Tableting Ltd, UK). 6 mm flat faced
punches were used at a compaction speed of 60
mm/min, with compression load ranging from
250 to 500 kg, with a 50 kg increment.
3. RESULTS AND DISCUSSION
3.1. Compressibility of LS admixtures
Regardless of the compaction pressure applied
and differences in liquid load, very high values
of solid fraction were observed in LS compacts
with Neusilin® US2 (0.90-0.94). On the other
hand, LS compacts with both Syloid® XDP
carriers exhibited lower relative density (0.59-
0.89) that was affected by changes in the
applied compaction pressure. Compressibility
profiles suggest that carrier particle size and the
amount of coating material used, had an effect
on relative density. An increase in the amount
of coating material used had a negative impact
on compressibility and lower values of solid
fraction were achieved.
3.2. Compactibility of LS admixtures
Admixtures N1 and N2 could be considered as
having good compactibility [3]. Compacts with
Neusilin® US2 achieved higher tensile strength
values compared to compacts with Syloid®
XDP, even at low compaction pressures.
Particle geometry and shape (Fig. 1) can affect
the way particles interact during tableting and
therefore may affect their mechanical
characteristics. Differences in particle size
could be a reason for lower values of solid
fraction and tensile strength observed in
compacts prepared with Syloid® XDP 3150
compared to compacts with Syloid® XDP 3050
as carrier.
Figure 1. SEM micrographies of LS particles:
admixture N1 (left) and S1 (right)
3.3. Tabletability of LS admixtures
Despite the significantly higher liquid load,
better tabletability was observed in LSS with
Neusilin® US2 as carrier with tensile strength
ranging from 1,68 to 2,55 and 1,61 to 2,11 for
formulations N1 and N2, respectively.
Although relatively similar values of tensile
strength were achieved, tabletability profiles
indicate that there are differences in compaction
behavior between formulations N1 and N2.
Higher values of tensile strength observed at the
same compression pressure indicate better
tabletability of LS admixtures with Syloid®
XDP 3050 compared to those with Syloid®
XDP 3150 as carrier. Interestingly,
formulations with Syloid® XDP 3050 had
higher liquid load which implies that this
formulation factor had lesser influence on
tabletability compared to the properties of the
carrier itself (such as particle size and specific
surface area). The lowest tabletability was
observed in LS admixtures S3 and S4 with
compact tensile strength lower than 1 MPa at all
but highest compaction pressure applied.
4. CONCLUSION
Out of the three investigated carriers, Neusilin®
US2 showed the best compaction properties
despite its high liquid load. LS admixtures with
this carrier exhibited the highest values of
tensile strength and solid fraction at relatively
low compression pressures. Pronounced
differences have been noticed between the two
Syloid carriers, which indicates the effect of
carrier particle size on compaction properties of
LS admixtures.",
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 = "Comparative compression characterization of liquisolid systems prepared with mesoporous carriers",
pages = "180-181",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4750"
}
