International Journal of Applied Pharmaceutics

ISSN- 0975-7058 Vol 10, Issue 2, 2018

Original Article
FORMULATION AND CHARACTERIZATION OF LAFUTIDINE NANOSUSPENSION FOR ORAL
DRUG DELIVERY SYSTEM

NOOR MOHAMMED DAWOOD*, SHAIMAA NAZAR ABDAL-HAMMID, AHMED ABBAS HUSSIEN

Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Iraq-Baghdad
Email: [email protected]
Received: 13 Oct 2017, Revised and Accepted: 09 Jan 2018
ABSTRACT
Objective: The objective of this study was to prepare nanosuspension of a practical water insoluble antiulcer drug which is lafutidine to enhance
the solubility, dissolution rate with studying the effect of different formulation variables to obtain the best formula with appropriate physical
properties and higher dissolution rate.
Methods: Nanosuspension of lafutidine was prepared using solvent anti-solvent precipitation method using Polyvinylpyrrolidone K-90(PVP K-90)
as the stabilizer. Ten formulations were prepared to show the effect of different variables in which two formulations showed the effect of stabilizer
type, three formulations showed the effect of stabilizer concentration, two formulations showed the effect of combination of polymer with
surfactant such as tween 80, three formulations show the effect of stirring speed and three formulations prepare to show the effect of addition of co-
surfactant such as tween 20. All these formulations are evaluated for their particle size and entrapment efficiency and in vitro release. The selected
one was evaluated for zeta potential, scanning electron microscope, atomic force microscopy, Fourier transforms infrared spectroscopy, differential
scanning calorimetry, saturation solubility and stability study.
Results: The formulations (F3-F10) were in the nano size. The optimum concentration of the stabilizer was in the formulation when the drug:
polymer: surfactant ratio 1:4:4 and the optimum stirring speed was 1500 rpm. Dramatic effect on the particle size reduction was found by the
addition of co-surfactant (tween 20) in formulation F7 that has a particle size 15.89±1.8 nm. The selected formula F7 showed an enhanced
dissolution profile (10 min) compared to the pure drug at all-time intervals.
Conclusion: The results show that the formulation that contains drug: PVP-K90: tween 80: tween 20 in ratio 1:4:2:2 is the best one and can be
utilized to formulate lafutidine nanosuspension.
Keywords: Lafutidine, Solubility, Dissolution rate, Bioavailability
© 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open-access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijap.2018v10i2.23075

INTRODUCTION Nanosuspension is a submicron colloidal dispersion of drug

particles. So a pharmaceutical nanosuspension is defined as a very
Approximately 75% of new chemical entities are poorly soluble in finely colloid, biphasic, dispersed, solid drug particles in the aqueous
aqueous medium and many even in the organic medium [1]. vehicle, with size below 1μm, without any matrix material, stabilized
Solubility is quantitatively defined as the concentration of solute in a by surfactants and polymers (stabilizer)[9].
saturated solution at a certain temperature, while qualitatively may
be defined as the spontaneous interaction of two or more substances Lafutidine is a yellowish white crystalline powder[10], with a
for formation of a homogeneous molecular dispersion [2]. So many melting point of (98.87-101.57 °C), It is freely soluble in glacial
problems arising from poor new drug solubility in drug research and acetic acid, DMF, soluble in methanol, sparingly soluble in
development. Also, low solubility limits the drug dissolution rate, dehydrated ethanol, very slightly soluble in ether, practically
resulting in low bioavailability of the oral drug [3]. As a result, insoluble in water with logp = 3.8 [11]. Lafutidine has pka =3.9 and
extensive attempts have been carried out to solve the problems of according to Biopharmaceutical Classification System (BCS), It
low aqueous solubility and increase the dissolution rate of belongs to class II of drug category [12].
hydrophobic drugs. Some of the conventional approaches are
particle size reduction method which subclasses into a) Lafutidine is a new H2-receptor antagonist, after absorption in the small
micronization: There are general methods of particle size reduction, intestine; it reaches gastric cells by the systemic circulation, then directly
such as milling and spray drying, rely upon mechanical stress to and quickly binds to gastric cell histamine H2 receptors, resulting in
disaggregate the active compound. In addition to that micronization prompt inhibition of gastric acid secretion. It is selectively absorbed from
approach successfully enhanced the bioavailability of poorly water- the upper part of small intestine (absorption window) [13]. The drug is
soluble drugs such as griseofulvin and felodipine [4, 5]. b) predominantly metabolized in the liver mainly by microsomal enzyme
nanonization: is the production of drug nanocrystals, and it is a CYP3A4, and CYP2D6 and its major metabolites are sulfonyl lafutidine
common approach to overcome poor drug solubility in water. and hydroxylated lafutidine [14]. Fasting plasma concentration of the
Nanonization produces drug particles below 1 micron either by the unchanged drug observed as Tmax: 0.8±0.1 h; Cmax: 174±20 ng/ml. It
bottom-up methods such as precipitation and self-assembly or top- has a biological half-life of 3.0 h [15].
down technologies such as milling and high-pressure homogenization. The aim of the study was to the formulation of lafutidine as
Nanonization has an advantage of increased saturation solubility of nanosuspension to improve its solubility and enhance in vitro
the drug together with the increase in dissolution rate [6]. dissolution rate.
Nanosuspensions technology has been conceived as a candidate for
efficient delivery of hydrophobic drugs and applied to poorly soluble
drugs since this technology results in the formulation that is having
high dissolution velocity and increased saturation solubility [7].
Other advantages of nanosuspension are that it can be easy
fabrication into a tablet or a capsule or dried nanosuspension form
which can easily be re-dispersible [8]. Fig. 1: Chemical structure of lafutidine [12]
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MATERIALS AND METHODS organic solution into the antisolvent solution by the help of a syringe
pump, under mechanical agitation of different speeds using homo
Materials disperser for 60 min at 25±1°C to allow organic solvent to evaporate
Lafutidine powder was purchased from Hangzhou hyper chemicals and get the desired nanosuspension [16]. The batches were prepared
limited, Zhejiang, China. Tween 80 and tween 20, was purchased according to the formulation design (table 1).
from Scharlau S. L Spain. (PVP K-90) was provided by Hangzhou
Evaluation of the prepared nanosuspension
hyper chemicals limited, Zhejiang, China. Dialysis membrane70
provided by HIMEDIA (Mumbai, India). All other chemicals and Particle size and size distribution
solvents were of analytical reagent grade, and deionized water also
was used in this study. Particle size determination was done by using Angstrom Advanced Inc.
ABT-9000 USA particle size analyzer which is a dynamic light scattering
Methods works by measuring the intensity of light scattered by the molecules in
Preparation of lafutidine nanosuspension by precipitation the sample as a function of time, at scattering angle 90° and a constant
method temperature of 25 °C. From the analysis, the average particle size which
is also called volume moment mean, (mean diameter in nm) reflects the
Nanosuspension precipitation method is used to prepare oral size of those particles which constitute the bulk of the sample volume
nanosuspension of lafutidine using a different concentration of and it was measured for all the prepared formulas. The polydispersity
polymer and surfactant. In brief, 10 mg of lafutidine was dissolved in index (PDI) which is a measure of the width of the size distribution of
an organic solvent (1 ml methanol). Deionized water containing the each formula of LAF nanosuspension also determined, it is a measure of
stabilizer (PVP K-90or tween 80) alone at the drug: stabilizer ratio 1:8 the distribution of particle size of nanoparticles obtained from a particle
or in the combination of PVP K-90 with tween 80 at the different analyzer, PDI is an index of spread or variation or width within the
concentration or in combination with co-surfactant (tween 20), which particle size distribution. Also, the analyzer determines the specific
acts as the antisolvent system. This was followed by the addition of the surface area of each sample [17].

Table 1: Composition of lafutidine nanosuspension formulation

Substance F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
LAF (mg) 10 10 10 10 10 10 10 10 10 10
PVP-K90 (mg) 80 - 50 40 30 50 40 30 50 50
Tween 80 (mg) - 74.8 28 37.4 46.7 14 18.7 23.4 28 28
Tween 20 (ml) - - - - - 13.6 18.2 22.7 - -
Methanol (ml) 1 1 1 1 1 1 1 1 1 1
Water (ml) 30 30 30 30 30 30 30 30 30 30
Stirring speed (rpm) 1500 1500 1500 1500 1500 1500 1500 1500 500 3000
F: formula, LAF: Lafutidine, PVP K-90: Polyvinylpyrrolidine k-90, rpm: round per min

Determination of entrapment efficiency (EE) of nanosuspension required as a minimum for physically stable nanosuspension
stabilized by electrostatic repulsion only. While zeta potential of
10 ml of nanosuspension was centrifuged at 6000 rpm for 20 min. about±20 mV is sufficient to of high-intensity the nanosuspension
The supernatant solution was filtered and separated. 1 ml of this system stabilized by a combination of steric and electrostatic
filtrate was diluted with water and the absorbance at maximum λ stabilization [20].
max was measured by UV spectrophotometer using water as blank
[18]. The amount of free drug in the formulations was measured and The freeze-drying of selected formula
the entrapment efficiency is then calculated from Eq.1
Freeze drying or lyophilization was carried out using christ (ALPHA
E. E% =
( – )∗
……. (1) 1-4 LD plus) to retrieve nanoparticles in a dried-powder state from
the nanosuspensions, to complete characterization of
The results were analyzed in triplicate and standard deviations are nanosuspension and show the effect of freeze drying on
reported. nanoparticles size and solubility so water-removal was conducted
through freeze-drying. The selected formula was used containing
In vitro dissolution profile of nanosuspension 2% w/w mannitol as the cryoprotectant, to prevent agglomeration
was frozen in a refrigerator at-70 °C for 24 h. Then the sample was
In vitro drug release for nanosuspension was done by using Himedia
lyophilized using vacuum freeze dryer at a controlled temperature
dialysis membrane (MWCO 12 KD). Volume containing 10 mg of
of (-44) °C and the pump operating at the pressure of 2.5 × 10
lafutidine of (F3-F10) nanosuspension was placed in the pretreated
pascals over the range of 48–72 hr. The obtained powder was used
dialysis bag and drug release was done using USP dissolution
for further studies [21].
apparatus II containing 900 ml of dissolution medium at 37 ± 0.5 °C.
The speed of the paddle was 100 rpm. The formulation of lafutidine Fourier transforms infrared spectroscopy (FTIR)
nanosuspension was subjected to the drug release studies in media
of 0.1N HCl (pH 1.2) in comparison with a pure drug. Samples (5 ml) The fourier transforms infrared spectroscopy spectra of pure
were withdrawn at intervals of 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, lafutidine and lyophilized powder of the selected formula were
100, 110 and 120 min respectively), and replenished with the obtained using FTIR spectrophotometer (FTIR-8300 Shimadzu,
equivalent volume of fresh dissolution medium to maintain the Japan) by potassium bromide (KBr) pellet method. This study was
constant volume. Then, samples were filtered and assayed achieved to identify any sign of interaction between the drug and
spectrophotometrically on UV spectrophotometer at 286 nm stabilizer used. The spectrum obtained was in between the wave
wavelength. The experiment repeated in triplicate for each number of 4000-400 cm-1[22].
formulation [19].
Scanning electron microscopy (SEM)
Zeta potential
Scanning electron microscope used for observing the morphology of
Zeta potential of the selected formulation of lafutidine samples, SEM of pure lafutidine, and lyophilized powder was
nanosuspension was measured by using (NanoSeries, Nano-ZS, confirmed by direct deposition of powder on double-sided carbon
Malvern Instruments, UK). A zeta potential value of±30mV is tape and coated with gold; the analysis of the particle size was

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performed using the UTHSCSA Image Tool software. Five to six high Statistical analysis
resolution and high magnification pictures of SEM representative of
the sample were used to find the particle size. The program was The experimental results are given as mean triplicate samples
used to measure the average size of the particles seen in each of the standard deviation (SD) and were analyzed according to one-way
analysis of variance (ANOVA) using Sigma Plot 11 software at which
SEM picture [23].
the results would be significant if p<0.05, and the results would be
X-ray powder diffraction nonsignificant if p>0.05.

Powder x-ray diffraction can be used to confirm the crystalline RESULTS AND DISCUSSION
nature of materials. So, this information is used to verify whether
Particle size analysis and polydispersity index measurement
the substances are crystalline or amorphous. The diffractograms
of lafutidine and lyophilized powders of the selected formulation The effect of different parameters on the particle size and polydispersity
were obtained for analysis. The study was confirmed by using index was studied using ten different formulations. The mean particle
Shimadzu XRD-6000 powder X-ray diffractometer at continuous size (effective diameter) for formulations varied in the wide range from
scan range of 10-80 degree. The operating voltage was 40 (kV) and 6.358±0.0 nm to 1188±1.7 nm. The particle size and PDI for different
current 30mA [24]. formulations of different parameters is showing in table 2.

Table 2: The particle size, and PDI of different formulations

Formula no. P. S.±SD* PDI±SD*
F1 1188±1.7 0.324±0.0
F2 805.2±1.7 0.489±0.0
F3 22.9±0.0 0.048±0.0
F4 73.0±11.9 0.893±0.0
F5 63.55±0.0 0.278±0.0
F6 19.08±0.0 0.405±0.0
F7 15.89±1.8 1.0±0.0
F8 6.358±0.0 0.196±0.0
F9 36.14±0.0 0.481±0.0
F10 59.5±0.0 0.703±0.0
*SD standard deviation, n=3, P. S.: Particle size, PDI: Polydispersity index

Effect of stabilizer type on the particle size and polydispersity index nm respectively, while in F3 in which tween 80 combined with PVP
K-90 at drug: polymer: surfactant ratio 1:5:3 the particle sizes were
Two formulations were used to show this effect F1, F2. The best 22.9 nm. That means the combination has the good surface affinity
stabilizer was in F2 (tween 80) which has particle size 805.2±1.7 and could form a substantial mechanical and thermodynamic barrier
nm. Also, this formulation show PDI in the value of 0.489 and this at the interface of drug molecule [29]. Polydispersity index values of
low value will indicate good stability of the nanosuspension. The F3 was 0.048, indicate that these formulas are monodisperse
effect of stabilizer type shown in the fig. 2. The choice of suitable standard, there are significant differences (p<0.05) from PDI values
stabilizers are the most important factors to control the size and of F1 and F2 that were 0.324-0.489 indicate that these formulas are
stability of the nanosuspension during nanoprecipitation methods midispersed standard.
[25]. Although; the mechanism of action of PVP K-90 which was used
as hydrophilic polymers to stabilize nanosuspensions physically by Effect of stabilizer concentration on the particle size and
steric stabilization; but they gave larger particle in ratios 1:8 drug: polydispersity index
stabilizer in F1(p<0.05) than particle size of F2 which contain tween
80, this may be attributed to the insufficient affinity of stabilizers to Three formulations were used to show this effect F3, F4, and F5. In fig.
drug molecule. However, if there is no affinity between the particle 4 the particle size of F5 containing PVP K-90 and tween 80 at drug:
surface and the polymer, the attractive forces between two particles polymer: surfactant ratio 1:5:3 was increased significantly (p<0.05)
become dominant due to depletion of polymer from the gap of two from 22.9 nm to 73 nm in F4 when the surfactant concentration raised
particles (depletion force) [26]. to drug: polymer: surfactant ratio 1:4:4 and then the particle size
decrease significantly (p<0.05) to 5.248 nm in F5.
Effect of combination of surfactant with polymer on particle
size and polydispersity index It was observed that with an increase in surfactant concentration in
the nanosuspension from the particle size of the nanosuspension
F3 was used to show the effect of combination of tween 80 (used as decreases. This was due to the decrease in relative viscosity, which
surfactant) with PVP K-90 (used as polymer) as compared with F1 led to decrease in particle size. It means that hydrodynamic
and F2 that used these stabilizers alone (fig. 3), When PVP K-90 used diameter of particle decreased with increase in the concentration of
as a primary stabilizer in F1, could not significantly decrease the the surfactant. The concentration of surfactant affected on particle
particle size (p>0.05) to nanosized particles; therefore, it could not size because too little concentration of stabilizer induces
be used as the single stabilizer for the nanosuspension. The use of agglomeration or aggregation and too much concentration promotes
tween 80 combined with another stabilizer (PVP K-90) as in fig. 3 Ostwald ripening [30].
may disperse drug particle into the aqueous solution and decrease
the particle size [27]. The combination of surfactant (tween80) with Effect of addition co-surfactant on particle size and poly-
PVP K-90 provide the electrostatic-steric mechanism, surfactant dispersity index
found to influence the particle size which helps in preventing growth
and stabilize the particles primarily by adsorption at the solid-liquid The addition of co-surfactant is also preferred for long-term
interface and reduction of the interfacial tension leading to an stabilization and decrease particle size significantly(p<0.05) as in
increased rate of nucleation [28]. fig. 5, F6-F8 studied the effect of the combination of surfactants
(tween 80 and tween 20) on the particle size that range 6.358-19.08
The most significant effect (p<0.05) of surfactant combination with nm which smaller than F3, F4 and F5 that contain one surfactant
one polymer was shown in formulas that contain tween 80 or PVP- (tween 80), these findings are in accordance with another study
K90 as primary stabilizer, as in F1and F2 respectively at ratio 1:8 whose particle sizes was lower and better stability when stabilized
(drug: primary stabilizer), the particle size was 1188 nm and 805.2 the formulation with surfactant mixtures compared with

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formulations with only one surfactant [31]. PDI of F8 and F6 were

0.196, and 0.405 respectively this show that these formulas were
dispersed while F7 was polydisperse because it had PDI equal to 1.0.
Effect of stirring speed on the particle size and polydispersity
index of prepared nanosuspension
Three different speeds 500, 1500 and 3000 rpm were used to
prepare three formulations F9, F3, and F10 to show this effect as in
fig. 6. In this study the optimums speed at the drug: polymer:
surfactant ratio 1:5:3 was found to be 1500 rpm that produce mean
particle size 22.9±0.0 nm. PDI of these formulations was in the range
of 0.048-0.703. The result suggested that lafutidine nanoparticles
were nonsignificantly affected (p>0.05) by stirring speed, the
decreased particle size with increased stirring speed is due to an
intensification of micromixing (i. e, mixing of molecular level)
between multi-phases. High micromixing efficiency increased mass Fig. 4: Effect of stabilizer concentration on the particle size of
transfer and the rate of diffusion between the multi-phases which nanosuspension (Results are expressed as mean, n=3)
induced high homogeneous supersaturation in short time, thus rapid
nucleation to produced smaller drug particle. In addition to that, a
high stirring speed prevents the particle growth by preventing their
aggregation. Hence the formation of smaller and more uniform drug
particles with high stirring speed [32].
However, further increase in the stirring speed led to increasing in
the particle size (p>0.05)of nanosuspension during precipitation
method that resulted in non-uniform formulations with visible
settling due to the aggregation of particles, this could be due to
mechanical agitation and non-uniform mixing producing local
regions of supersaturation during anti-solvent precipitation [33].

Fig. 5: Effect of addition of co-surfactant on particle size (n=3)

Fig. 2: Effect of stabilizer type on the particle size of

nanosuspension (Results as an as mean, n=3)

Fig. 6: Effect of addition of stirring speed on particle size

(Results are expressed as mean, n=3)

Drug entrapment efficiency

The Percentage drug entrapment efficiency of the formulations was
calculated and the results were 95.604%, 98.54%, 96.34%, 98.43%,
98.74%, 98.54, 94.56% and 97.5 for F3, F4, F5, F6 F7, F8, F9 and F10
respectively. The drug entrapment efficiency of F7 was high when
compared to other formulations. Drug entrapment efficiency was
significantly affected by the addition of non-ionic surfactants
(combination of tween80 with tween 20) with ratio of drug:
polymer: surfactant (1:4:4) with higher EE% (98.74%) in F7 (fig. 8)
which could be due to decreased partitioning of LAF into the outer
Fig. 3: Effect of a combination of the surfactant with polymer on aqueous phase and better dispersion obtained by adding a
the particle size of nanosuspension (n=3) hydrophilic surfactants [34].

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Fig. 7: Particle size distribution of the selected formula (F7)

Fig. 8: Drug entrapment efficiency of the prepared formulation of lafutidine nanosuspension (Results are expressed as mean, n=3)

In vitro dissolution study another formula. This formula is selected for zeta potential
measurement study, lyophilization, and further study.
The dissolution profile of the formulas that in nanosize (F3-F10)
were studied in 0.1N HCl of pH 1.2 to determine the best formula Zeta potential
that gives the best release in first 10 min. The release of F3-F10 is
presented 0.1N HCl of pH 1.2 in fig. (9). From the study, the results The zeta potential for the selected formulation of lafutidine
showed that the formula F7 that contain PVP K-90, tween 80 and nanosuspension was-23 mV as shown in fig. 11. The charge was
tween 20 stabilizers gave the best release in 10 min in comparison negative due to adsorbed tween 80, tween 20 and PVP K-90 on the
with other formulas and the formula shows a maximum cumulative drug particles; however, this result of zeta potential proposes that
percentage drug release of 100 % within 10 min. the nanosuspension was adequately stabilized. It reflects the
electrical potential of particles and is influenced by the composition
From the above result depending on the particle size and PDI will be of the particles and the medium in which it is dispersed. Zeta
the formula no. F7 which has the mean particle size (15.89±0.0 nm) potential gives certain information about the surface charge
and E. E% (98.74). F7 was considered as the selected formula properties and furthers the long-term physical stability of the
because it had the highest dissolution rate, highest entrapment nanosuspension. The obtained value for selected formulation
efficiency percentage and low particle size when compared with indicates stable nanosuspension [35].

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Fig. 9: In vitro drug release profile of lafutidine formulation nanosuspension in 0.1N HCl at 37±0.5 °C (n=3)

Fig. 10: In vitro drug release profile of selected formula (F7) compared with pure powder lafutidine in 0.1N HCl at 37±0.5 °C (Results are
expressed as mean, n=3)

Fig. 11: Zeta potential of the selected formula (F7)

Saturation solubility of freeze-drying nanosuspension study indicated that pure lafutidine had a very low solubility in
water(0.078 mg/ml) which considered as practically insoluble in
The batch F7 (lafutidine: PVP K-90: tween 80: tween 20 1:4:2:2) was water, while the saturation solubility of lafutidine nanoparticle in
selected for freeze drying. In this study, 2% of mannitol was added lyophilized powder was (125.5 mg/ml) greater than that of pure
as the cryoprotectant for avoiding nanocrystals aggregation/ drug which considered as freely soluble in water. This may be due to
agglomeration. Mannitol containing samples showed good re- the reduction in particle size of lafutidine to nano size which results
dispersibility upon manual shaking. The results of the solubility in exposure of more surface area and enhanced hydrophilicity; these

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were responsible for the significantly enhanced (p<0.05) saturation (F7) intensity in fig. 12 (B). FTIR spectra of lafutidine
solubility [36]. nanosuspension show no change in shifting the position of the
lafutidine nanosuspension functional groupspeak and this will
Fourier transforms infrared spectroscopy indicate there was no an interaction between the drug and the
The Fourier transforms infrared spectra of pure lafutidine shown in stabilizer PVP K-90 and other excipients (tween80 and tween 20)
fig. 12 (A) and that of the lyophilized powder of the selected formula used in the formulation [37].

B
Fig. 12: Fourier transforms infrared spectroscopy of A) lafutidine and B) lyophilized powder

Scanning electron microscope elucidated the irregular shape with the rough surface of PVP K-90
particle because it was the amorphous polymer [38].
Scanning electron microscope of pure lafutidine, PVP K-90 and
lyophilized powder are presented in fig. (13, 14, and 15) at 1K, 5K, Scanning electron microscope of lyophilized powder at 1K, 5K, 10K
10K, 50K and 500x (this only for PVP K-90) magnification. The and 50K of magnification revealed that the decreased the particle
scanning electron microscope study for pure lafutidine powder size with some of the crystalline needle structure of drug this
showed large particles with crystalline needle shape with the problem may mean that by the addition more stabilizer and more
smooth surface, while scanning electron microscope of PVP K-90 cryoprotectant.

A B

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C D
Fig. 13: Scanning electron microscope of pure lafutidine (A, B, C, and D) at 1K, 5K, 10K and 50K magnification respectively

A B

C D

E
Fig. 14: Scanning electron microscope of PVP K-90 (A, B, C, D, and E) at 1K, 5K, 10K, 50K and 500X magnification respectively

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A B

C D
Fig. 15: Scanning electron microscope of lyophilized powder (A, B, C, and D) at 1K, 5K, 10K and 50K magnification respectively

Fig. 16: Powder X-ray diffraction analysis of pure lafutidine

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Powder x-ray diffraction analysis (PXRD) the polymer [39]. However, the characteristic crystalline peak at the
2θ angle of 20.3 ° became lower intensity peak, and strongest peaks of
To confirm the physical state of lafutidine, PVP K-90 and lyophilized 17.2 °, 19.8 ° disappeared in the pattern of lyophilized powder as in fig.
powder x-ray diffraction were performed. The Powder X-ray 18 producing another peak at the 2θ angle of 5.69 ° and 20.6 °. This
diffraction analysis patterns of lafutidine as a pure drug exhibited study suggested that there was no significant difference in
intense crystalline peaks at the 2θ angle as in fig. 16, the strongest characteristic peaks position of lafutidine in the lyophilized powder.
three peaks were 17.2 °, 19.8 °, and 20.3 °. The diffraction patterns of Accordingly, all types of energy input during preparation and the
PVP K-90 demonstrated in fig. 17. PVPK-90 indicated the halo pattern attendance of stabilizer did not change the crystallinity of lyophilized
was revealing amorphous nature of polymer as in it’s diffractogram nanosuspension powder. A just difference detected between the
and characterized by low intense peak. However, the strongest peaks coarse powder, and lafutidine nanosuspension was in the peak
of PVP K-90 at the 2θ angle were 11.29 °, 43.9 and 64.29 °. The intensity and presented of high-intensity peaks, probably attributed to
diffused peaks at higher angles confirm the semi-crystalline nature of particle size reduction, stabilizer at the surface [40].

Fig. 17: Powder x-ray diffraction analysis of the PVP K-90

Fig. 18: Powder X-ray diffraction analysis of the selected formula F7

CONCLUSION The process parameters, such as stabilizer type, the combination of

the surfactant with the polymer, stabilizer concentration, stirring
It may be concluded from the results of this study that speed and combination of other stabilizer were investigated and
nanosuspensions of particle water-insoluble drug lafutidine can be optimized to produce the smallest drug nanoparticles. The
prepared using solvent anti-solvent precipitation method and using dissolution rate of the nanosuspension significantly enhances as
PVP K90, tween 80, and tween 20 as stabilizers. compare with the pure drug.

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ACKNOWLEDGEMENT 19. Sahu BP, Das MK. Nanosuspension for enhancement of oral
bioavailability of felodipine. Appl Nanosci 2014;4:189-97.
We are very thankful to College of Pharmacy, University of Basrah, 20. Papdiwal A, Pande V, Aher S. Investigation of an effect of
Iraq; for providing necessary facilities utilized in carrying out parts different stabilizers on a formulation of zaltoprofen
of the work. nanosuspension. Int J Pharm Sci Rev Res 2014;27:244-9.
AUTHORS CONTRIBUTIONS 21. Deore S, Nerkar P, Mahajan H, Ige P. Formulation and
evaluation of nanosuspension formulations polymers. Int J
All the author have contributed equally Pharm Sci Nanotechnol 2014;8:5-14.
22. Gadad AP, Naik SS, Dandagi PM, Bokmal UB. Formulation and
CONFLICT OF INTERESTS
evaluation of gastroretentive floating microspheres of
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