Pharmaceutics, Drug Delivery and Pharmaceutical Technology
Liquid Oil Marbles: Increasing the Bioavailability of Poorly
rej Rychecký, Ale
Department of Chemical Engineering, Chemical Robotics Laboratory, University of Chemistry and Technology Prague, Technick
a 5, 166 28 Prague 6,
Received 18 December 2018
Revised 23 January 2019
Accepted 28 January 2019
Available online 2 February 2019
liquid oil marbles
Many new therapeutic candidates and active pharmaceutical ingredients (APIs) are poorly soluble in an
aqueous environment, resulting in their reduced bioavailability. A promising way of enhancing the release
of an API and, thus, its bioavailability seems to be the use of liquid oil marbles (LOMs). An LOM system
behaves as a solid form but consists of an oil droplet in which an already dissolved API is encapsulated by a
powder. This study aims to optimize the oil/powder combination for the development of such systems.
LOMs were successfully prepared for 15 oil/powder combinations, and the following properties were
investigated: particle mass fraction, dissolution time, and mechanical stability. Furthermore, the release of
API from both LOMs and LOMs encapsulated into gelatine capsules was studied.
©2019 American Pharmacists Association
. Published by Elsevier Inc. All rights reserved.
During recent years, the number of poorly water-soluble drugs
The solubility in water is, however, one of
the most important parameters of drug usage and drug delivery.
For some substances, it is possible to obtain a pharmacological
response even at a very low concentration (e.g., hormones),
whereas for the others (antibiotics, etc.), higher concentrations are
required. Hence, the solubility issue emerges. Low bioavailability of
newly discovered active pharmaceutical ingredients (APIs) is one of
the most challenging pursuits in pharmaceutical development,
especially for orally administered drugs.
The bioavailability of such
APIs is mostly limited during their release followed by the ab-
sorption in the gastrointestinal tract. Several approaches, mostly
based on physical and chemical modiﬁcation of the drug sub-
stances, have been reported to enhance their solubility and thus
bioavailability. The physical modiﬁcation includes particle size
reduction (micronization, nanosuspension),
(amorphous form, co-crystallization),
and drug dispersion (solid
Changing pH, salt formation, and complexation are
techniques that belong to the category of chemical modiﬁcation.
Another technique for dissolution enhancement of poorly
water-soluble drugs is liquisolid technique.
This technique is
described as the incorporation of active substances as a liquid phase
(solution, suspension, or emulsion) into highly porous support
(solid state) to form a dry nonsticking powder with properties
suitable for further processing. The advantages of such a technique
are the low production cost, increased bioavailability, and the
possibility to prepare pharmaceutical forms with controlled release
ability and pH-independent drug release proﬁle.
On the other
hand, this technique is not suitable for drugs with a high dose of API
because the oil content is only 17%-36% and thus a large tablet must
Incorporating a poorly soluble drug into liquid phase and
transforming this system into a solid form represents a novel
approach to increase its bioavailability. Liquid oil marbles (LOMs)
can be considered as such incorporation, where the LOM is formed
from liquid droplet covered by powder. Liquid marbles (LMs) were
ﬁrst presented in 2001 by Aussillous and Qu
aqueous LMs. The LMs behave as soft solids, which gives them
excellent nonwetting and nonadhesive properties in contact with
various surfaces. Particles of the coating powders do not absorb
inside of the liquid core and stay on the surface in comparison with
In recent years, aqueous LMs have been intensively studied.
On the contrary, only a few reports exist about LMs with encap-
sulated oil instead of aqueous phase. The preparation of LOMs is a
much more challenging task than liquid aqueous marbles
due to the relatively low surface tension of many oils and relatively
high surface energy of many solid particles. Potential uses of LMs
Abbreviations used: API, active pharmaceutical ingredient; LM, liquid marble;
LOM, liquid oil marble; PTFE, polytetraﬂuoroethylene; SEM, scanning electron
This article contains supplementary material available from the authors by request
or via the Internet at https://doi.org/10.1016/j.xphs.2019.01.026.
*Correspondence to: Jitka
a (Telephone: þ420 220444460).
E-mail address: Jitka.Cejkova@vscht.cz (J.
Contents lists available at ScienceDirect
Journal of Pharmaceutical Sciences
journal homepage: www.jpharmsci.org
0022-3549/©2019 American Pharmacists Association
. Published by Elsevier Inc. All rights reserved.
Journal of Pharmaceutical Sciences 108 (2019) 2136-2142
have been studied and tested for a variety of applications such as
microﬂuidics, miniature reactors, sensors, accelerometers, and gas
storage and pressure-sensitive adhesives because of their ability to
encapsulate functional materials.
The LOMs are different in the
ratio between the solid and liquid phases by comparison with LMs.
The LOMs can contain around 10%-15% of oils relative to the total
mass, whereas LMs can contain up to 90% of aqueous phase.
The main goal of this article was to design and prepare a capsule
containing LOMs with a poorly water-soluble drug (API). A wide
range of materials, both oils and powders, were tested to fabricate
stable LOMs (stability regarding at least a few weeks). Based on the
characterization of oils and powders concerning the preparation of
LOMs, the best combination was chosen to fabricate a gelatine
capsule with encapsulated LOMs.
Materials and Methods
The following powders were used for fabrication of the LOMs:
agarose, aluminum hydroxide, calcium carbonate, carbon SLG,
carboxymethylcellulose, D-sorbitol, dextran, gelatine, glucose,
hydroxypropyl methylcellulose, chitosan, lactose, maltodextrin,
methylcellulose, polytetraﬂuoroethylene (PTFE, 35
m), and yeast
extract (all from Sigma-Aldrich), wheat ﬂour (Penam, Brno, Czech
Republic), sodium alginate (SAFC), starch (Natura, Czech Republic),
glycine and sodium hydroxide (Penta, Prague, Czech Republic). As
oil phase, rapeseed oil (Br€
olio), macadamia oil (Saloos, Opava, Czech
Republic), and castor oil (Saloos) were used. Other chemicals used
for the experiments were sodium ﬂuoride (Penta), Avicel (Fluka),
ethanol (Sigma-Aldrich), potassium chloride (Lachner, Neratovice,
Czech Republic), and gelatine capsules (Zentiva, Praha-Dolní
echolupy, Czech Republic).
Liquid Oil Marble Preparation
The preparation procedure for LOMs was as follows. The solid
powders were spread on a Petri dish, and a single oil droplet was
dropped onto it (10, 20, 50, and 100
L). A positive displacement
pipette (Gilson Microman Positive Displacement M50 or M1000)
was used for handling viscous oils. The oil droplet (placed on the
powder) was gently shaken in a circular motion to ensure complete
coverage of the oil droplet surface by the particles of the powder (to
form liquid oil marble), and the fabricated LOM was carefully
transferred to a separate Petri dish.
The physical properties of oils (viscosity, density, and surface
tension) were characterized. The rheological properties of oils
were determined by the rotational viscometer Rheolab QC (Anton
Paar) at 25
C, over a wide range of shear rates (from 10 to 160 s
corresponding to 2.32 to 37.14 rpm, respectively). The shear
stress, shear rate, viscosity, and velocity were also measured. The
drop shape analysis method (Theta; Biolin Scientiﬁc) was used to
determine the surface tension (oil-air interface), and the surface
tension was calculated using the Young-Laplace ﬁt. The loading
capacity of API in oils was experimentally measured as follows: 1
g of APIs was mixed with 9 g of oil for 2 h on a magnetic stirrer
(at 600 rpm). In the next step, 0.5 g of API was added and mixed
at 600 rpm for 2 h, and if the API was completely dissolved, this
step was repeated until the maximal loading capacity of the oil
The size distribution of particles was measured by static light
scattering in a ﬂow cell (Horiba Partica LA 950V2) and evaluated
using the Fraunhofer kernel. Ethanol was used as a disperse phase
for the measurement as the particles are not soluble in ethanol.
Particles morphology was investigated by scanning electron
microscopy (SEM; Jeol JCM-5700). The samples were coated with
5-nm-thin gold layer, to prevent charging during SEM measure-
ment, using the sputter coater Emitech K550X.
The drop shape analysis system (Theta; Biolin Scientiﬁc) was
used to determine the time-dependent contact angle between
liquid (castor, macadamia, and rapeseed oils) and powders
(aluminum hydroxide, lactose, methylcellulose, starch, and yeast
extract). A pellet (10 mm in diameter, applied pressure of 7 metric
tons) was made from each powder using the Carver 4350 Bench Top
Laboratory Pellet Press.
Mass Fraction of Solid Particle Evaluation
The pipetted volume used for formation of liquid oil droplet was
Þto precisely deﬁne the mass of the oil core (each
measurement was repeated 10 times); 10 LOMs were fabricated
and weighted ðm
Þ. The total mass of LOMs was evaluated, and
mass fraction was calculated according to Equation 1:
Þis the mass of the particles, m
mass of the LOMs, and w
is the mass fraction of adhered and
absorbed particles in the oil droplet.
The size of the LOMs was evaluated using image analysis (NIS-
Elements). The picture of a Petri dish with LOMs was taken from the
top view using the camera (digital camera Olympus E-620).
The Stability of Liquid Oil Marbles
The mechanical stability and elasticity of LOMs were analyzed
by the texture analyzer (Brookﬁeld CT3, TA44)d10 samples for a
given combination of oil and powder. The texture analyzer was set
to press the LOMs to the 50% of their size, the test speed was set to
0.1 mm/s and the distance traveled by the probe as a function of the
load was recorded. The stability of LOMs in time was also tested.
Fabricated LOMs were placed into the Petri dish (laboratory con-
C), and every day, LOMs were observed, shaken, and a
picture of them was taken to investigate their long-term stability.
Dissolution Study of APIs From the Liquid Oil Marbles
The dissolution study of LOMs formed from 10
L of the oil
phase with dissolved APIs was performed. For release experiments,
an LOM was placed in a vessel ﬁtted with 200 mL of hydrochloric
acid-potassium chloride buffer (pH 1.4) and kept at 37 ±0.5
rotating speed of 120 rpm. The hydrochloric acid-potassium chlo-
ride buffer was prepared by mixing 50 mL of 0.2M potassium
chloride with 41.4 mL of 0.2M hydrochloric acid. The API release
from LOMs was measured at a speciﬁc wavelength of given API
(250 nm) by time-dependent UV/vis spectrophotometry (Pion
DISS Proﬁler). The release rate from the LOMs was compared to
the dissolution rate of pure APIs in the buffer. The dissolution study
was performed in triplicates.
a et al. / Journal of Pharmaceutical Sciences 108 (2019) 2136-2142 2137
Capsules Containing Liquid Oil Marbles
The LOMs (10
L of the oil phase with dissolved APIs) were ﬁlled
into hard gelatine capsules and put into the dissolution vessels. The
composition of the gelatine capsule was gelatine (44%), glycerol
(24%), and water (32%), and the internal volume of the gelatine
capsule was 0.81 mL (size 0). Hydrochloric acid-potassium chloride
buffer (100 mM, pH 1.4) was used as a medium for dissolution
experiments. A single capsule was placed in 1000 mL of hydro-
chloric acid-potassium chloride buffer and kept at 37 ±1
C with a
rotating speed of 120 rpm. The time-dependent UV/vis spectrum
was measured. The dissolution study was performed in triplicates.
Results and Discussion
In this study, LOMs are demonstrated as a new approach to
increasing the dissolution rate and, thus, the bioavailability of a
poorly soluble drug. Suitable combinations of oil and powder for
the fabrication of LOMs were experimentally investigated with the
aim of enhancing drug release after oral administration.
The Interaction Between Powders and Oils: An Initial Parametric
Our initial parametric study was performed with 20 different
powders, including PTFE, the most common material for the
preparation of aqueous LMs, and rapeseed oil. The handbook of
was used to identify suitable powder
candidates for the fabrication of drug carriers for in vivo use. When
an oil droplet was dropped onto the powder and followed by gentle
shaking, 4 different cases were observed (see Fig. 1).
Case 1 represented the formation of a “perfect”LOM and was only
observed for PTFE powder. The LOM was stable, and the volume of
the oil phase leaked out when the LOM was cut in half. This indicates
that the PTFE particles were not present in the oil phase. Thus, PTFE
particles are an ideal material for the fabrication of LOMs. PTFE
particles are commonly used for the preparation of LMs (with an
aqueous core) because of their hydrophobic character. Furthermore,
PTFE particles are also known as a material that repels oils because of
their oleophobic properties
; however, PTFE microparticles are not
approved by the Food and Drug Administration as excipients for oral
delivery and thus were excluded from our further studies.
In case 2, rapeseed oil soaked through the layer of particles and
no LOM or any other structured particle was formed. This was
observed for carbon SLG, carbopol, carboxymethylcellulose,
glycine, maltodextrin, and sodium alginate. Consequently, these
powders were also excluded from our further investigations.
In case 3, an LOM was formed; however, after cutting the LOM
with a scalpel (at room temperature), a large number of particles
were found to be present in the oil phase. Case 3 was observed for
aluminum hydroxide, dextran, ﬂour, lactose, starch, and yeast
In case 4, similar marbles as in case 3 were formed. Moreover,
there was swelling of the whole LOM. Case 4 was observed for the
following powders: agarose, Avicel, calcium carbonate, D-sorbitol,
gelatine, glucose, hydroxypropyl methylcellulose, chitosan, potas-
sium chloride, and sodium ﬂuoride.
Although cases 3 and 4 did not correspond to “perfect”LOMs
(i.e., a liquid-oil core covered by a shell consisting of solid particles
as in case 1) and the coating particles were also present inside the
oil core, it still fulﬁlled the requirement that the oil was encapsu-
lated within the powder and that the whole structure behaves as a
soft solid without any leakage of the oil content. Therefore, selected
powders from cases 3 and 4 were chosen for LOM preparation.
From 3 groups of chemical structures (inorganic, high molecular
weight, and sugar), 5 powders were chosen. Based on interaction
with oils, at least one representative powder was chosen from each
group. From the ﬁrst group, the inorganic compound aluminum
hydroxide was chosen. From the highemolecular weight group,
methylcellulose and starch were chosen. Lactose was selected from
the third group. Although yeast extract does not ﬁt into the deﬁned
groups, it was chosen for further studies because of its interesting
behavior in our preliminary studies.
Oil Characterization: Castor Oil or Macadamia Oil as Potential
The basic physicochemical properties are the key parameters of
a liquid core used in the fabrication of LOMs. Because of this,
Figure 1. Four cases observed during LOM preparation. (a) Case 1, liquid oil marble in
which the particles cover only the droplet surface. (b) Case 2, no liquid oil marble
formation. (c) Case 3, liquid oil marble with some particles dispersed in the oil phase.
(d) Case 4, liquid oil marble with some particles dispersed in the oil phase combined
with its swelling.
Summary of Density, Loading Capacity of API in Oils, Surface Tension, and Viscosity
Physical Properties of Oils Castor Oil Macadamia Oil Rapeseed Oil
) 966 915 920
Loading capacity of API (g API/g oil) 0.72 0.44 0.28
Surface tension (mN/m) 34.0 30.4 31.9
Viscosity (mPa s) 401 40.1 45.9
Figure 2. Size distribution of the particles dispersed in ethanol.
a et al. / Journal of Pharmaceutical Sciences 108 (2019) 2136-21422138
3 different types of oils (castor, macadamia, and rapeseed) were
chosen for the investigation. All of them are used in the pharma-
Their key physicochemical parameters were
measured (Table 1, data obtained at an ambient temperature of
C). In accordance with the literature,
as viscosity increased,
the coverage of the aqueous LM by powders decreased. Moreover,
the solubility of an API in an appropriate oil is an important
parameter that plays a key role in the mass ratio of the API in the
ﬁnal product. Both surface tension and loading capacity provided
clear evidence that castor oil was the most appropriate oil for the
fabrication of LOMs.
Optimal Physical Properties of Powders Used for LOMs' Fabrication
Size, morphology, and wettability are the key parameters of
powders used in the fabrication of LOMs. According to McEleney
particle size affects the preparation of LMs such that the
attainable surface coverage decreases as the particle mass increases.
Figure 3. Scanning electron microscope images of particles used for LOM preparation. Left column: magniﬁcation 100. Right column: magniﬁcation 1000(acceleration voltage
a et al. / Journal of Pharmaceutical Sciences 108 (2019) 2136-2142 2139
The authors also reported that a large particle size leads to a high
ratio of powder mass per surface area. Therefore, particle size dis-
tribution was measured (Fig. 2) and SEM was used to investigate the
microstructure of the particles (Fig. 3.) It has been reported
ﬁne particles move around easily and envelope the liquid core,
thereby maintaining the integrity of the shell; however, because
large particles are more rigid and inﬂexible, they do not protect the
internal phase against contact with the support. In the case of an oil-
air system, partially oleophobic particles are important for stabili-
zation of the oil-in-air materials, such as LOMs.
wettability between oil and powders is likely to be a key parameter
in the formation of LMs. Compared with the other powders initially
tested, aluminum hydroxide had the lowest contact angles with
castor, macadamia, and rapeseed oils (Table S2); aluminum hy-
droxide was the material most wetted by the oils. This may be due to
the narrow particle size distribution and smooth surface of
aluminum hydroxide powder. On the other hand, yeast extract
reached very high contact angles, (especially with castor oil) which
could be inﬂuenced by the irregular morphology of its grain surface.
Characterization of Liquid Oil Marbles: Best Combinations of Powder
and Oil for LOM Preparation
Mechanical Stability of LOMs
Four different oil-phase volumes (10, 20, 50, and 100
used to fabricate LOMs. Although the LOMs formed from the
smallest volume were stable in all cases (see Fig. S1), those con-
taining a higher oil volume (50 or 100
L) were not always stable.
In fact, at 100
L, the oil leaked out and the investigated LOMs
(all oil/powder combinations) collapsed. This led us to conclude
that stable LOMs require an oil volume of 20
L or less.
Long-term stability tests of the 20
L LOMs (1, 20 and 30 days,
Fig. S2) showed that they remained stable during the investigated
time frame. Unlike aqueous LMs, within which evaporation of the
aqueous core takes place, LOMs remained stable for a longer time.
Although, under some conditions, degradation/oxidation of the oil
may occur (see Mechanical Stability of LOMs Under External Force),
the stability of LOMs appears to make them suitable candidates for
application in drug formulation.
Mechanical Stability of LOMs Under External Force
Because the ability to ﬁll LOMs into a gelatine capsule is desired,
information about their mechanical stability under force is crucial to
identifying the most favorable oil/powder combinations. The me-
chanical stability of LOMs during their handling before usage, stor-
age, and transportation depends on their hardness. The hardness of
LOMs was measured by using the texture analyzer where the load
required to squeeze an LOM in half was evaluated (see The Stability
of Liquid Oil Marbles). During the compressive stress tests, 2
different responses of the LOMs were observed (see Fig. 4).
In the ﬁrst case, an LOM crushed before squeezing into the half
of the original size. Such results were observed for LOMs fabricated
from aluminum hydroxide. The maximum loads for crushing these
LOMs were found to be 98, 72, and 73 mN with castor oil, macad-
amia oil, and rapeseed oil, respectively; however, after crushing, no
oil was visible inside the LOMs because of the chemical reaction
that takes place between the aluminum hydroxide and the oils.
Castor oil reacts with aluminum hydroxide to produce glycerol and
castor acid aluminum salt. Rapeseed oil is more complex because it
contains more acids, primarily through oleic acids. Hence, the re-
action between triacylglycerol and aluminum hydroxide leads to
the production of glycerol and oleic acid aluminum salt. In the case
of macadamia oil, the main ingredient is also triacylglycerol.
Overall, these results suggest that LOMs containing aluminum hy-
droxide are not suitable potential candidates for use as API carriers.
In the second case, the LOMs were squeezed by the texture
analyzer to half of their original size while remaining compact
(Fig. 5) and the force response of the LOMs to the deformation was
measured. The LOMs prepared from methylcellulose and rapeseed
oil required the highest load (332 mN ±87 mN) compared with
aluminum hydroxide (with all types of oils), which required load of
around 80 mN. Because methylcellulose has a wide particle size
distribution and rough particle surface, a much higher load is
required (200-300 mN depending on the oil) to squeeze the LOMs.
On the other hand, aluminum hydroxide has the smallest particles
(mean size of approximately 9
m) of all of the investigated pow-
ders. It also has a narrow particle size distribution and smooth
particle surface (Fig. 3) compared with the other powders. These
properties resulted in a much smaller load (72 mN ±10 mN) being
required to crush LOMs made from aluminum hydroxide.
Mass Fraction of Particles Stabilizing the LOMs
The composition of the LOMs was experimentally investigated
with the aim of determining the mass fraction of particles adhered
to and absorbed on/in them (see Fig. 6). For their application, LOMs
must have the smallest mass fraction of particles possible, and
leakage of the oil phase must be avoided. According to the litera-
LMs could contain up to 98% liquid phase. Nquyen et al.
reported that particles smaller than 50
m form multilayers,
whereas large/rigid particles form monolayers around the oil
droplet. Likewise, Eshtiaghi et al.
found that surface coverage
decreases as particle size increases. This means that the mass
fraction of particles in LOMs could also be inﬂuenced by particle
size distribution. On the other hand, a multilayer surface helps the
Figure 4. Liquid oil marbles after squeezing: (a) crushing of a liquid oil marble from macadamia oil and aluminum hydroxide and (b) squeezing of a liquid oil marble from
macadamia oil and yeast extract.
a et al. / Journal of Pharmaceutical Sciences 108 (2019) 2136-21422140
liquid core to avoid contact with the wetting surface as this makes
the powder shell dense. Methylcellulose was identiﬁed as the most
suitable powder for the preparation of LOMs.
Release Efﬁciency of Model Drug From LOMs
The release efﬁciencies of our LOMs were compared to the
dissolution rates of pure APIs in an aqueous environment. As a
reference dissolution time, 90% API dissolution in 60 ±5 min was
used. The time required for the release of 90% of the available API
content is summarized in Table 2, and examples of the full release
curves presented in Figure S3. The available API content was
deﬁned as the amount when the released API amount becomes
constant in time. Some amount of the API remains in the oil phase
because of the higher solubility of API in oils than in the aqueous
The fastest API release was observed in the case of yeast
extract with castor oil (90% API release within 6 min). Conversely,
the release of the API from LOMs composed of lactose took
approximately 40 min. The release rate from aluminum hydroxide
was approximately 1.5 times slower than the dissolution of the API
in aqueous buffer. Again, this shows that LOMs prepared from
aluminum hydroxide are not suitable for further testing and usage.
In conclusion, 15 combinations of LOMs were fabricated and
characterized, with the focus on their mechanical and long-term
stability, on the mass fraction of solid particles in the LOMs, and
on their ability to carry and release poorly water-soluble APIs.
The LOM combinations were plotted using a spider diagram
(Fig. S4). The following LOMs covered the largest area: methyl-
cellulose/rapeseed oil and methylcellulose/macadamia oil. Over-
all, methylcellulose/macadamia oil appears to be the best
candidate for the fabrication of LOMs because of (1) high solu-
bility of APIs in macadamia oil and (2) mass fraction of particles
in these LOMs was lower than that in the methylcellulose/rape-
Time Required for Release of 90% of the API From LOMs
Powder Castor Oil
Aluminum hydroxide 95 ±28 101 ±689±2
Lactose 37 ±249±840±9
Methylcellulose 39 ±131±850±15
Starch 70 ±14 50 ±739±1
Yeast extract 6 ±234±448±10
The oil-phase volume was 10
L, and initial API concentrations were 0.72, 0.44, and
0.28 API (g)/oil (g) in castor, macadamia, and rapeseed oils, respectively.
Figure 6. Mass fraction of particles adhered to and adsorbed in/on LOMs (volume of
the oil phase was 10
L). The error bars were evaluated from 10 experiments with the
indicated oil types.
Figure 5. (a) Example of the displacement curve of methylcellulose with macadamia
oil (the dashed line represents the LOM compression, and the solid line represents the
retraction). (b) Maximum load required for compressing the LOM in half.
Figure 7. Example of release from capsule containg 10 LOMs (macadamia oil and
methylcellulose) or pure API.
a et al. / Journal of Pharmaceutical Sciences 108 (2019) 2136-2142 2141
For use in the pharmaceutical industry, LOMs could be sealed
into a gelatine capsule. Macadamia oil and methylcellulose were
chosen to test this because of their lower mass fraction and higher
load stability when being squeezed (182 mN). Smaller LOMs
fabricated from 10
L of the mixture (macadamia oil with API) and
methylcellulose were placed in the ﬁnal dosage form. On a mass
basis, the ﬁnal composition of the LOM was 6% API, 56% macadamia
oil, and 38% methylcellulose powder. Ten LOMs were transported to
each capsule. The capsules achieved 90% API release in 59 ±14 min
(Fig. 7). By comparison, after oral administration of the API alone,
the maximum concentration is reached after 2-4 h for tablets and
1-2 h for solution form.
In this article, a novel concept of drug delivery based on LOMs
was experimentally investigated. LOMs are gaining importance in
the pharmaceutical industry. This system can increase the disso-
lution rate and bioavailability of poorly soluble drugs. We have
shown that LOMs could be an appropriate substitute for the liqui-
solid formulations as some combinations (macadamia oil with
methylcellulose) reach quite high oil content, means high dissolved
APIs. LOMs were sufﬁciently stable to resist stress in the capsule.
Moreover, LOM composition changes the speed of API dissolution.
LOM is a promising and innovative technology because of the
simple manufacturing process, low production cost, and sustained
release formulations, having water-insoluble drug exhibit zero or-
der release. To our best knowledge, we are the ﬁrst to report the
usage of LOMs for enhancing the release rate of poorly water-
soluble APIs. Therefore, we are already working with various APIs
to verify the capability of LOMs.
C. would like to gratefully acknowledge support from the Czech
Science Foundation (17-21696Y). P.J. would like to thank the Spe-
ciﬁc University Research (MSMT No 21-SVV/2018) for ﬁnancial
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