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IJPAR |Volume 2 | Issue 4 | Oct -Dec- 2013 ISSN: 2320-2831

Available Online at: www.ijpar.com

[Research article]

Formulation and Evaluation of Moxifloxacin Loaded Alginate Chitosan

Nanoparticles
*R.Devi damayanthi, Dr.C.B.Tharani1, Dr.N.Narayanan2.
*Department of Pharmaceutics, Madras Medical College, Chennai, India.
1
Department of Pharmacology, Saveetha medical college, Chennai, India.
2
Department of Pharmaceutics, Jaya college of Pharmacy, Chennai, India.

ABSTRACT
The main objective of this study was to prepare and evaluate Alginate chitosan nanoparticles containing
Moxifloxacin by ionic gelation method. The influence of different experimental parameters on the entrapment
efficiency (EE), drug loading (DL), rate of recovery, percent drug released etc was evaluated. SEM indicated
that nanoparticles have discrete spherical structure without aggregation. The average particle size was found to
be 105.2±8nm. The in vitro drug release behaviour from all drug loaded batches was found to be sustained
release over a period of 96 hours. Nanoparticles were stored at different temperatures and humidity as per ICH
guidelines to check the stability.
Key words: Moxifloxacin, Nanoparticles, Tuberculosis, Ionic gelation method, Alginate.

INTRODUCTION nanoparticles include chitosan, alginate, albumin,

One of the most key areas of research in drug gelatin, polyacrylates, polycaprolactones,poly(D,
delivery today is the design of nano systems that L-lactide-co-glycolide) and poly (D, L-lactide)
are able to deliver drugs, to the site of action, at However, there are concerns about polymeric
appropriate time in optimum dosage. These nanoparticles including cytotoxicity of by-products
nanocarriers are sub micron particles containing (although some, such as polyanhydrides, degrade
entrapped drugs which might prevent or minimize into products that are biocompatible) and
the drug degradation and metabolism as well as scalability.Tuberculosis (TB) caused by the
cellular efflux1,2 . Some other applications of bacterium Mycobacterium tuberculosis, is a major
nanoparticles include possible recognition of infectious burden worldwide and statistical
vascular endothelial dysfunction3; oral delivery of estimates continue to worsen with each passing
insulin4; brain drug targeting for neurodegenerative year. Tuberculosis affects one third of the world
disorders such as Alzheimer’s disease5; topical population, i.e. nearly 2 billion individuals, also
administration to enhance penetration and responsible for 3 million death annually. India
distribution in and across the skin barrier6; and pH- accounts for 20% of all new TB cases in the world
sensitive nanoparticles to improve oral each year8, 9. Antimicrobial agents, which are
bioavailability of drugs such as cyclosporine A7. effective against Mycobacteriumtuberculosis, are
Some polymers used in the fabrication of widely available10. A fluoroquinolone antibiotic,

* Corresponding author: R. Devi Damayanthi..

E-mail address: [email protected]
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moxifloxacin is active against M. tuberculosis al. Calcium chloride (18 mM) was added dropwise
being as potent as rifampicin11. The present study for 60 min under magnetic stirring into beaker
was performed to determine feasibility of containing sodium alginate solution (0.05%) to
encapsulation of moxifloxacin within alginate provide alginate pregel. The different concentration
chitosan nanoparticles. of drug (25 to 100 mg) is added to the alginate
pregel solution .Then 25 ml of Chitosan solution
MATERIALS AND METHOD (0.06%) was added followed by stirring for 30 min
Low molecular weight chitosan with a deacetylated and the mixture was kept at room temperature
grade of about 75-85% was purchased from Sigma overnight. The pH of alginate and chitosan
Aldrich. Moxifloxacin were supplied as gift sample solutions was initially set to 4.9 and 4.6,
by Macleods Pharmaceuticals Ltd, Mumbai, India. respectively. A colloidal dispersion at pH 4.7
Sodium alginate and calcium chloride were formed upon polycationic chitosan addition,
purchased from SD Fine Chemicals, Mumbai, India (visible as the Tyndall effect) 12. Drug loaded
nanoparticles were recovered by centrifugation at
Preparation of Moxifloxacin Nanoparticles 15000 rpm for 30-45 min and the obtained
Moxifloxacin nanoparticles were prepared by the sediment then was suspended in water. These two
principle involving cation induced controlled purification steps were repeated twice. The purified
gelification method reported by Rajaonarivony et particles were lyophilized.

Table: 1 Formulation of Moxifloxacin Nanoparticles.

Formulation Polymer ratio Drug concentration

(alginate:chitosan) (mg)
MF1 6:5 10
MF2 6:5 25
MF3 6:5 50
MF4 6:5 100

Evaluation of Moxifloxacin Nanoparticles

Nanoparticles were separated from aqueous Physical Characterization of Nanoparticles
medium by ultra centrifugation at 35000 rpm for 30 The formulations which showed higher
min. Drug loading in nanoparticles and encapsulation efficiencies, drug loading and rate of
encapsulation efficiency were determined by recovery, smaller particle size, poly dispersity
measuring the leftover drug in the supernatant and index (PDI) lesser than 0.5, better surface charge
washing fluids. The supernatant and the washing (zetapotential) was chosen for morphology
fluid were collected in 50 ml plastic tubes. The assessment and in vitro release study. The sizes of
solution was diluted accordingly and filtered. The the nanoparticles were determined by dynamic
amount of drug present in the solution was laser light scattering (DLS) (Nanoserious, Malvern
analyzed by UV spectroscopy13 . The encapsulation Instruments, UK).The particle size distribution is
efficiency, drug loading and rate of recovery were reported as PDI. . The zeta potential of the
determined using the following equation. nanoparticles was also obtained by zetasizer
(Malvern ZS, UK). The morphology of the
Encapsulation Efficiency nanoparticles was observed by scanning electron
(Estimated Drug content/Theoretical drug content) microscopy.
X100
In vitro Release Studies
Dug Loading Efficiency In vitro release of Moxifloxacin from alginate-
(Estimated drug content/Weight of product) X100 chitosan nanoparticles was determined using, the
release media, simulated lung fluid in order to
Rate of recovery simulate the condition in the lungs. Freeze-dried
(Weight of product/ Weight of drug and polymer) × formulations were taken in the dialysis bag
100 (molecular weight cit off 1000-12000 Da). The

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dialysis bag is suspended in 100 ml of the of drug increases Encapsulation Efficiency

dissolution medium on magnetic stirrer at 37+0.5 C decreases. The drug loading increases with increase
at 100 rpm and the amount of nanoparticles was in concentration of drug but after attaining
varied in order to keep constant the amount of optimum amount (50 mg), it decreases on further
drug. A measure of 1 ml samples were withdrawn increasing the concentration. Maximum drug
at appropriate time intervals. Same volume of loading and encapsulation was found in
dissolution medium was replaced to maintain a formulation (MF3) having drug concentration of 50
constant volume. The withdrawn samples were mg. This is due to fact that drug loading is limited
diluted suitably with SLF and absorbance of the and increasing drug concentration led to higher
resulting solution was measured at 289 nm by UV amount of free drug and lower EE. Zeta potential
spectrophotometer. The cumulative amount of of optimized formulation (MF3) was found to be
drugs was obtained from the calibration curve of +36.2 mV. The rate of recovery was highest
Moxifloxacin in Simulated Lung Fluid (SLF) 11. (76.1±3.2%) in formulation MF 3 shown in the
The test was done in triplicate. table 2. . The in-vitro release profile of all
formulation is shown in figure. 2. Among the three
Stability Study formulations, formulation MF3 had a pronounced
The stability studies were carried using the sustained release of 67.93+ 0.1 over a period of
optimized batch MF3 as per the ICH guidelines. four days with burst release in the first four hr was
The stability of drug loaded nanoparticles was equivalent to 34.67+0.6%. SEM photographs are
evaluated in terms of its drug Loading, entrapment shown in figure 3.The particles shape was found to
efficiency, percentage of drug released etc be fairly spherical structure without aggregation.
(Aterman, 2007). The optimized formulation was subjected to
stability studies at a room temperature and 40 °C /
RESULT AND DISCUSSION 75% RH. The optimized formulation was evaluated
Moxifloxacin nanoparticles with varying for zeta potential, particle size and percent drug
proportions of Moxifloxacin and alginate-chitosan release. Negligible changes were seen in different
polymer were prepared by ionic gelation method.. physicochemical parameters at a room temperature
The particle size of nanoparticles varied between as well as 40°C/ 75 % RH. There was no
105.2 ±8 to 315±4 nm among the different significance difference in in-vitro release after
formulations. The results of physiochemical three-month stability study at both room
characterization revealed that as the concentration temperature and accelerated conditions (Table 3).

Table: 2 Physiochemical characterization of Moxifloxacin Nanoparticles

Formulation Encapsulation Drug Rate of Particle PDI Zeta

Efficiency Loading recovery Size Potential
% % % (nm) (mV)
MF1 86.5±1.3 50.6±3.2 52.4±2.4 256±4.3 0.52 +30
MF2 84.2±2.1 62.4±4.3 76.1±4.2 105.2±3.5 0.42 +36.2
MF3 74.2±3.2 65.2±5.2 70.2±3.2 315±5 0.56 +28

Figure:1 Effect of concentration on Encapsulation Efficiency and Drug Loading

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Figure 2 : In vitro release profile of optimized formulation(MF3)

Figure 3:Morphology of Moxifloxacin loaded Nanoparticles

Table 3: Stability studies Physiochemical Characterization of Moxifloxacin

Nanoparticles.

Formulation Encapsulation Drug Rate of Particle PDI Zeta In vitro

Efficiency Loading recovery Size Potential releease at 96
% % % (nm) (mV) hrs (%)
MF2 82.2±2.3 60.2±1.3 74.1±3.2 108.2±3.5 0.45 +34.4 70.56±2.4

CONCLUSION hrs. On the bases of experimental data this

Thus from the whole research work, it can be formulation was considered as optimized
concluded that the objective of proposed research formulation.
work has been fulfilled and polymeric
nanoparticles of Moxifloxacin has been prepared ACKNOWLEDGEMENT
using alginate chitosan- polymer. Formulation MF3 We are thankful to College of Pharmacy, Madras
found to have spherical shape, encapsulation Medical College, Chennai and S.R.M. College of
efficiency of 84.2±2.1, drug loading of 62.4±4.3, Pharmacy, Potheri, Chennai for providing research
and in vitro release of 67.93+ 0.1 at the end of 96 facilities.

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