Formulation and Evaluation of Liquid
Nanocrystals of Sorafenib Tosylate
Nagaraju Diddi*, Shravan Kumar Y, Pavani S and Neelima P
Department of Pharmaceutics, Vaagdevi College of Pharmacy, India
Submission: August 18, 2019; Published: October 03, 2019
*Corresponding author: Nagaraju Diddi, Department of Pharmaceutics, Vaagdevi College of Pharmacy, India
How to cite this article: Nagaraju D, Shravan K Y, Pavani S, Neelima P. Formulation and Evaluation of Liquid Nanocrystals of Sorafenib Tosylate.
Glob J Pharmaceu Sci. 2019; 7(5): 555721. DOI: 10.19080/GJPPS.2019.07.555721.
The liquid crystalline state has both the properties of liquid and solid. The liquid state is found to associate with flow property whereas the solid state has structural properties of crystallinity in aspects of orientation and position. Liquid crystalline phases represent intermediate states and are also called as mesophases.
The studies were done with different formulations to ensure its controlled drug release and bioavailability.
Context: Nanoparticles helps in site specific targeting which aids in controlled release of the incorporated drugs. Site specific targeting can be achieved by attaching targeting ligands to surface of particles with the help of magnetic field influence.
Aim and objective: To ensure that nanoparticles will provide control release of the drug which are used as drug carriers for lipophilic molecules there by which it enhances the solubility and bioavailability of poorly water-soluble drug by reducing their doses regimen as a drug delivery system.
Methods and material: Simple emulsification followed by high pressure homogenisation
Results: FTIR Studies, Characterization of particle size, entrapment efficiency and total drug content.
Conclusions: Liquid crystal nanoparticles provide controlled release of the drug and these systems are used as drug carriers for lipophilic drugs, to enhance the solubility and bioavailability of poorly water-soluble drugs and to reduce the doses regimen through nanoparticles, as a drug delivery system.
Keywords: Nanocrystals; Targeted Delivery; Bioavailability; High Pressure Homogenization; Scanning Electron Microscope; Ultrasonication; Poloxamer 407 And Glycerol Mono Oleate
Nanoparticles are defined as particulate dispersion or solid particles with size in range of 10-1000 nm. Polymeric nanoparticles are made from non-biodegradable and bio-degradable polymers. Sorafenib is a potent anticancer agent for the treatment of hepatocellular carcinoma. It exists in crystalline as well as amorphous form, of these later exhibits higher bioavailability owing to improved solubility [1-3]. Solubility can be improved by mechanisms like co-solvency, complexation, chemical modification, hydrotropy, size reduction and changing crystal morphism etc. To compare the surface area of different materials quantitatively, the term specific surface area is used. This is defined as the surface area per unit weight or volume of material. As surface area increases, solubility increases .
The goals of pre-formulation studies were meant to select a suitable drug substance, evaluate its physical and chemical properties and understand the material’s stability under the conditions that will enforce the development of a drug delivery system. It Establishes compatibility with excipients and enhances physico-chemical properties and determines its kinetic release rate profile [5-9].
Sorafenib tosylate, Glycerol mono oleate, and Poloxamer 407.
Preparation of standard curve
10mg of Sorafenib tosylate was dissolved 10mL of 7.4 pH
buffer (stock solution) 1mL solution was taken and make up
with 10mL of 7.4 pH (10μg/mL) containing 2, 4, 6, 8, 10μg/
mL of sorafenib per mL of solution [10-12]. The absorbance
of the above dilutions was measured at 264 nm by using UVSpectrophotometer
taking 7.4 pH buffer as blank. Then a graph
was plotted by taking concentration on X-Axis and absorbance
on Y-Axis which gives a straight-line Linearity of standard curve
which was assessed from the square of correlation coefficient
(R2) which determined by least-square linear regression
Preparation of sorafenib liquid crystal nanopaticles
Formulations containing 10mg Sorafenib were prepared
by emulsification technique to study the effect of method of
manufacture on drug release with the help of High-pressure
homogenization. High pressure homogenization (HPH) is a
reliable and powerful technique for the preparation of liquid
crystal nanoparticles [14-16]. High pressure homogenizers tend
to push the liquid with high pressure (100-2000 bar) through a
narrow gap (in the range of a few microns). The fluid accelerates
on a very short distance to very high velocity (over 1000km/h).
Very high shear stress and cavitation forces disrupt the particles
down to the submicron range. Typical lipid contents are in the
range 5-10% and represent no problem to the homogenizer .
Method of preparation
The Excipients were weighed and moltened separately in
a china dish over a water bath. Drug was added to the molten
polymer and mixed well . After thorough mixing the china
dish was removed from water bath and cooled. The coherent
mass was then treated for high pressure homogenization [19-
22] (Table 1).
The standards and requirements were maintained
accordingly and an accurately weighed portion of the powder
equivalent to about 10mg of Sorafenib tosylate was transferred
to a 10mL volumetric flask containing 7.4 pH. It was shaken
by mechanical means for 1h then it was filtered through a
Whattman filter paper (No.1) and diluted to 1mL with 7.4 pH.
and absorbance was measured against blank at 264nm .
In vitro drug release studies
The In vitro drug release study was performed for all the
tablets using Franz diffusion cell apparatus under the following
Dissolution test parameters
Medium: 25mL of 7.4 pH buffer
Rotation speed: 50rpm
Sampling volume: 5 mL
Sampling time: 0.5, 1, 2, 3, 6, 9, 12 hours
The samples withdrawn were filtered through Whatman
filter paper (No.1) and drug content in each sample was
analyzed by UV-visible spectrophotometer at λ max 264nm [25-
27] (Figure 1) (Table 2).
Compatibility of the Sorafenib tosylate with polymers was
studied and FTIR spectral analysis was carried out to identify
the changes in chemical composition of the drug after combining
with the excipients. The pure drug mixture was mixed properly
Placed under Bruker FTIR scanned in wavelength. The spectra
were analyzed and interpreted  (Figure 2) (Tables 3 & 4).
Particle Size, zeta potential and Polydispersity index of
prepared LCNs: All the prepared samples were analyzed in order
to determine their particle size distribution, zeta potential and
PDI values  (Figure 3) (Table 5).
Sorafenib tosylate liquid crystal nanoparticles were
successfully prepared by high pressure homogenization followed
by the ultrasonication method along with bath sonication by
using ingredients such as glycerol mono oleate, poloxomer
407. Various formulation factors on particle size, zeta potential,
polydispersity index, entrapment efficiency, drug content, in
vitro and ex vivo studies were also studied
Formulation F1 with poloxamer 407 with lipid and glycerol
monooleate concentration 2:1 showed lower particle size of
142nm, zeta potential -34.1 mV, polydispersity index of 0.324
with uniform dispersion, along with the highest entrapment
efficiency 91.86% and drug release of 90.03% .
Liquid crystal dispersion prepared using Poloxamer 407
(1.5%) as stabilizer [F4] showed lower particle size than the
other surfactants irrespective of the lipids studied [32-34]. This
result has been explained due to the higher molecular weight of
Poloxamer 407 and higher HLB value of Poloxamer 407. Thus, it
could be well concluded that the amount of drug released was
much slower and controlled from the liquid crystal dispersions
prepared by using glycerol monooleate as the lipid matrix, with
poloxamer 07 as the surfactant, than that from the sorafenibpure
drug solution From correlation coefficient (R2 ) value of
different kinetic models, it was found that the formulation (F4)
sorafenib –dispersion containing poloxamer 407 and glycerol
monooleate in the ratio of 1:4 showed R2 of 0.9748 of which
followed Higuchi model with ‘n’ value of 0.7382 indicating drug
release followed non-fickian diffusion .
The sorafenib tosylate liquid crystal nanoparticles with
the application of high-pressure homogenizer followed by ultrasonication method along with the bath sonication turned out
to be a useful method for the successful incorporation of the poor
water-soluble drug sorafenib with high entrapment efficiency.
Furthermore, it could be presumed that if the nanometer range
particles were obtained, the bioavailability might be increased.
Hence, we can conclude that liquid crystal nanoparticles provide
controlled release of the drug and these systems are used as
drug carriers for lipophilic drugs, to enhance the solubility and
bioavailability of poorly water-soluble drugs and to reduce the
doses regimen through nanoparticles, as a drug delivery system.
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