Users Online: 20 | Home Print this page Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2012  |  Volume : 2  |  Issue : 2  |  Page : 78-82

Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride

Department of Industrial Pharmacy, Bapuji Pharmacy College, Davangere, Karnataka, India

Date of Web Publication24-Aug-2012

Correspondence Address:
Sonjoy Mandal
Department of Industrial Pharmacy, Bapuji Pharmacy College, Davangere-577004, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2230-973X.100042

Rights and Permissions

Background/Aim: The aim of the present investigation is to prepare and evaluate in situ gel-forming ophthalmic drug delivery system of moxifloxacin hydrochloride. Materials and Methods: Sodium alginate, a novel ophthalmic gel-forming mucoadhesive polymer, which gets converted to gel in the presence of divalent-cations (calcium ion) present in the lachrymal fluid, was used as the gelling agent. Hydroxy propyl methyl cellulose (HPMC) is a mucoadhesive polymer used as viscosity enhancer. Suitable concentrations of buffering agents were used to adjust the pH to 6.5. All the formulations were sterilized in an autoclave at 121°C for 15 minutes. The formulations were evaluated for clarity, pH measurement, gelling capacity, drug content estimation, rheological study, in vitro diffusion study, antibacterial activity, isotonicity, and eye irritation study. Results: The developed formulations exhibited sustained release of drug from formulation over a period of 10 hours thus increasing residence time of the drug. The optimized formulations were tested for eye irritation on albino rabbit (male). The formulations were found to be non-irritating with no ocular damage or abnormal clinical signs to the cornea, iris or conjunctiva observed. Conclusion: These in situ gelling systems containing gums may be a valuable alternative to the conventional systems.

Keywords: Gelling capacity, in situ gel, in vitro diffusion study, moxifloxacin hydrochloride, rheological evaluation

How to cite this article:
Mandal S, Thimmasetty MK, Prabhushankar G L, Geetha M S. Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int J Pharma Investig 2012;2:78-82

How to cite this URL:
Mandal S, Thimmasetty MK, Prabhushankar G L, Geetha M S. Formulation and evaluation of an in situ gel-forming ophthalmic formulation of moxifloxacin hydrochloride. Int J Pharma Investig [serial online] 2012 [cited 2019 Feb 15];2:78-82. Available from:

  Introduction Top

Major problem in ocular therapeutics is the attainment of optimal drug concentration at the site of action, which is compromised mainly due to precorneal loss resulting in only a small fraction of the drug being ocularly absorbed. The effective dose administered may be altered by increasing the retention time of medication into the eye by using in situ gel-forming systems. Ophthalmic drug delivery is an extremely interesting and highly challenging endeavor. [1],[2] The anatomy, physiology, and biochemistry of the eye render this organ exquisitely impervious to foreign substances. The challenge to the formulator is to circumvent the protective barriers of the eye without causing permanent tissue damage. [3] Ophthalmic ointments ensure superior drug bioavailability by increasing the contact time, minimizing the dilution by tears, and resisting nasolacrimal drainage. Major disadvantage of ointment, providing blurred vision, due to this it could be used either night time or for treatment on the outside and edges of the eyelids. Suspension as ophthalmic delivery systems relies on the assumption that particles may persist in conjunctival sac. Precorneal drug loss can be minimal, such as retarding drainage by using diffusion-controlled, nonerodible polymeric insert. The major disadvantage of inserts is the lack of patient acceptance owing to difficult administration. The development of newer, more sensitive diagnostic techniques and therapeutic agents render urgency to the development of more successful ocular delivery systems. The primitive ophthalmic solution, suspension, and ointment dosage forms are clearly no longer sufficient to combat these diseases, and current research and development efforts to design better therapeutic systems are the primary focus of this research work. The aim of the present investigation is to formulate an in situ gel using novel gum system. In situ gel solution increases the residence time and also sustain the release mechanism of the drug.

  Materials and Methods Top

Moxifloxacin hydrochloride was obtained from Torrent Pharmaceuticals, Ahemadabad, India. Sodium alginate and HPMC-E 50LV was obtained from the nice chemicals, Ahmedabad, India. HPMC-K 4M was obtained from Signet Chemicals, Japan. Benzalconium chloride was obtained from S.D Fine chemicals, Mumbai, India. All the polymers received were of pharmaceutical grade and were used as received. Other materials and solvents used were of analytical grade. Distilled water was prepared in laboratory using all glass distillation apparatus.

Preparation of in situ gel

The polymeric solution was prepared by dispersing required quantity of sodium alginate as main polymer and HPMC- E 50 LV, HPMC- K4M as co-polymers in water using a magnetic stirrer until the polymers completely dissolve. Aqueous solution of moxifloxacin hydrochloride was added in to the polymeric solution with continuous stirring. [4] Buffering and osmolality agents were added to the resulting solution along with benzalkonium chloride. The pH of the solution was adjusted to 6.5 using 0.1 N NaoH/0.1 N HCl. The in situ gel formulations are depicted in [Table 1].
Table 1: Formulation design of in situ gelling system

Click here to view

Physical parameters

The formulated in situ gel solution was tested for clarity, pH, gelling capacity, and drug content estimation. The results are as shown in [Table 2].
Table 2: Evaluation parameters of formulations

Click here to view

Gelling capacity

The gelling capacity of the prepared formulation was determined by placing a drop of the formulation in a vial containing 2 ml of freshly prepared simulated tear fluid and visually observed. The time taken for its gelling was noted. [5],[6]

Rheological studies

The viscosity measurements were carried out using Brookfield viscometer LVDV-E model. The in situ gel formulations were placed in the sampler tube. The samples were analyzed at 37°C ± 0.5°C by a circulating bath connected to the viscometer adaptor prior to each measurement. [7],[8],[9],[10] The angular velocity of the spindle was increased 1 to 4 and the viscosity of the formulation was measured.

Drug content estimation

The drug content estimation was carried out by diluting 1 ml of prepared formulation in 100 ml of distilled water and analyzed using UV-visible spectrophotometer (Shimadzu UV-1700 PC, Shimadzu Corporation, Japan) at 290 nm.

In vitro drug release studies

The in vitro release of moxifloxacin hydrochloride from the prepared formulations was studied using a modified diffusion testing apparatus. The freshly prepared simulated tear fluid (pH 7.4) was used as a diffusion medium. Semi permeable membrane, previously soaked in the diffusion medium for overnight, was tied to one end of a specially designed glass cylinder (open at both ends) having inner diameter of 3.4 cm. Two milliliter of formulation was accurately pipette into the glass cylinder known as donor chamber. The cylinder was suspended in a beaker (Acceptor chamber) containing 100 ml of diffusion medium so that the membrane just touches the surface of the medium. Acceptor chamber was maintained at a temperature of 37 ± 2°C with a stirring rate of 50 rpm using magnetic stirrer. About 1 ml of sample was withdrawn at a time interval of 1 hour and replaced with an equal volume of fresh diffusion medium. The aliquots were diluted with the diffusion medium and analyzed at 290 nm using UV spectrophotometer. In a similar manner, 2 ml of pure drug solution (0.5% w/v in distilled water) and 2 ml marketed product (MILFLOX) were studied in a similar manner.

Antimicrobial Activity

Antimicrobial activity was determined by agar diffusion test employing cup plate technique. The drug was allowed to diffuse through a solid agar medium. The standard minimum inhibitory concentration (MIC 2 μg/ml) of control and developed formulations containing moxifloxacin were prepared. A total of 60 ml of nutrient agar media was prepared and sterilized at 15 lb/sq-inch pressure for 18 minutes in an autoclave; 0.5 ml of microorganism suspension was poured into the above medium which is maintained at temperature of 52°C to 58°C. This will be done in an aseptic condition. Immediately 20 ml of the microbial agar suspension was poured into each petriplate. After solidification of the media, sterile solutions of moxifloxacin hydrochloride (standard solutions) and the developed formulations diluted suitably with sterile distilled water (test solutions) were poured in to the cup of sterile nutrient agar Petri plates. This was previously seeded with test organisms ( Escherichia More Details coli and Staphylococcus aureus). After allowing diffusion of the solutions for 2 hours, the agar plates were incubated at 37°C for 24 hours. The Zone of inhibition (ZOI) was measured around each cup and compared with that of control. The entire operation was carried out in a laminar airflow unit. Each formulation solution was tested in triplicate. Both positive and negative controls were maintained throughout the study. [11]

Ocular irritancy

Ocular irritation study was performed on optimized formulation in four albino rabbits (male), each weighing about 2 to 3 kg, and 0.1 ml of the optimized sterile moxifloxacin hydrochloride formulation was instilled in to cul-de-sac twice a day for a period of 14 days. The rabbits were monitored periodically for redness, swelling, watering of the eye. [12]

Accelerated stability studies

Optimized sterile formulation was subjected to stability testing. Sterile optimized ophthalmic formulation was filled in glass vials, closed with gray butyl rubber closures and sealed with an aluminium caps. The vials contain optimized formulation were kept in stability chamber, maintained at 40 ± 2°C and 75 ± 5 % RH for one month. Samples were withdrawn weekly and estimated for drug content, pH, visual appearance, gelling capacity and in vitro drug release. [13]

  Results and Discussion Top

In the present investigation, efforts were made to prepare the sustained release moxifloxacin hydrochloride in situ gel forming ophthalmic solution using polymers such as sodium alginate and HPMC. Sodium alginate a novel ophthalmic gel-forming mucoadhesive polymer, which gets converted to gel in the presence of divalent-cations (calcium ion) present in the lachrymal fluid (pH 7.4), was used as the gelling agent.

The prepared in situ gel formulations were evaluated for clarity, pH measurement, gelling capacity, drug content estimation, rheological study, in vitro diffusion study. The pH of in situ gel solution was found to be around 6.5 for all the formulations. The formulation should have an optimum viscosity that will allow for easy instillation into the eye, which would undergo a rapid sol to gel transition (triggered by ion exchange) as shown in [Table 2].

Rheological evaluation of all the formulation exhibited Newtonian flow before gelling and exhibited pseudoplastic flow after gelling in the eye. There was increase in the viscosity after gelling. Additionally, the gel formed in situ should maintain its integrity without dissolving or eroding for a prolonged period. Results are as shown in [Table 3] and [Figure 1] and [Figure 2].
Figure 1: Formulations F1 to F6 (Before gelling)

Click here to view
Figure 2: Formulations F1 to F6 (After gelling)

Click here to view
Table 3: Rheological studies of formulations

Click here to view

From the in vitro results it was observed that percentage release of the drug from the developed formulations F1 (93.86%), F2 (92.78%), F3 (89.97%), F4 (82.80%), F5 (80.49%), and F6 (78.71%) as shown in [Figure 3]. Formulation F6 showed more sustained release compared to other formulations. This could be the reason of higher concentration of Sodium alginate and HPMC K4M among the developed formulations. By observing the drug release profile it can be conclude that release is not stagnant even end of 10 hours. Formulation F6 showed highest zone of inhibition values against S. aureus (28.66 mm) and E. coli (30.99 mm), respectively, compared to other developed formulations. Hence, F6 formulation was taken for further study.
Figure 3: Comparative in vitro diffusion profile of pure drug, marketed product and F1 to F6 formulations

Click here to view

Antimicrobial efficacy study was performed on F6 formulation using Gram +ve S. aureus and Gram -ve E. coli organism. The zone of inhibition of F6 ophthalmic formulation found to be 28.66 and 30.99 mm, respectively, for Gram +ve S. aureus and Gram -ve E. coli organism. The results of antimicrobial activity are as shown in the [Table 4]. The study indicated moxifloxacin hydrochloride retained its antimicrobial activity when formulated as gel forming ophthalmic system against both selected S. aureus and E. coli.
Table 4: Zone of inhibition values of formulation F1 to F6 and pure drug at the concentration of 2 μg/ml against Staphylococcus aureus and Escherichia coli

Click here to view

Ocular irritation study was performed using healthy albino rabbits after getting prior permission from the institutional animal ethics committee. The eyes of each rabbits were examined at particular time interval after instillation of the optimized formulation (F6). There was no redness, continuous blinking, swelling or watering of eyes. No ocular damage or abnormal clinical signs to the cornea, iris or conjunctiva were visible. The result of ocular irritation studies indicates that formulations containing all ingredients are non-irritant to rabbit eye.

Accelerated stability studies were carried out at 40 ± 2°C at 75 ± 5 % RH for 1 month using stability chamber. The samples were analyzed periodically on every week, and found that there are no changes in visual appearance, clarity, pH, and gelation. Assay values after 1 month of storage are found almost same (deviating not more than one percent). Release profiles were similar to that of zero days.

  Conclusion Top

Moxifloxacin hydrochloride, a broad spectrum antibacterial agent used in the treatment of ocular infections, was successfully formulated as in situ gel-forming eye drops using Sodium alginate as a gelling agent in combination with HPMC as a viscosity enhancing agent. Thus, the developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain drug release. Also important is the ease of administration afforded and decreased frequency of administration resulting in better patient acceptance.

  References Top

1.Ashim KM. Ophthalmic drug delivery system. Vol 58. New York: Marcel Dekker Inc; 1993. p. 105-10.   Back to cited text no. 1
2.Kaur IP, Garg A, Singla AK, Aggarwal D. Vesicular systems in ocular drug delivery an overview. Int J Pharm 2004;269:1-14.   Back to cited text no. 2
3.Singh SK, Bandyopadhyay P. Pharmacia Corporation. Ophthalmic formulation with novel gum composition. US 7128928, 2006.  Back to cited text no. 3
4.Thorsteinn L, Tomi J. Cyclodextrins in ocular drug delivery. Adv Drug Del Rev 1999;36:59-78.   Back to cited text no. 4
5.Gokulgandhi MR, Parikh JR, Megha Barot M, Modi DM. A pH triggered in situ gel forming ophthalmic drug delivery system for tropicamide. Drug Delivery Technology 2007;5:44-9.  Back to cited text no. 5
6.Zhidong L, Jiawei L, Shufang N, Hui L, Pingtian D, Weisan P. Study of an alginate/HPMC based in situ gelling ophthalmic delivery system for gatifloxacin. Int J Pharm 2006;315:12-7.   Back to cited text no. 6
7.Indu PK, Manjit S, Meenakshi K. Formulation and evaluation of ophthalmic preparations of acetazolamide. Int J Pharm 2000;199:119-27.   Back to cited text no. 7
8.Pandit D, Bharathi A, Srinatha R, Singh S. Long acting ophthalmic formulation of indomethacin: Evaluation of alginate gel systems. Indian J Pharm Sci 2007;69:37-40.  Back to cited text no. 8
9.Johan C, Katarina E, Roger P, Katarina J. Rheological evaluation of gelrite in situ gel for opthalmic use. Eur J Pharm Sci 1998;6:113-6.   Back to cited text no. 9
10.Katarina E, Johan C, Roger, P. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. Eur J Pharm Sci 1998;6:105-12.   Back to cited text no. 10
11.Srividya B, Cardoza RM, Amin PD. Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. J Control Release 2001;69:379-88.  Back to cited text no. 11
12.Draize J, Woodward G, Calvery O. Methods for the study of irritation and toxicity of substance applied topically to the skin and mucous membrane. J Pharm Col Exp Ther 1994;82:377-90.  Back to cited text no. 12
13.Mathews BR. Regulatory aspects of stability testing in Europe. Drug Dev Ind Pharm 1999;25:831-56.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 Smart gel system of Linum usitatissimum mucilage as a vehicle of an ophthalmic drug
Sobia Noreen,Mahira Arshad,Shazia Akram Ghumman,Shazia Noureen,Muhammad Zubair Malik,Syed Nasir Abbas Bukhari
Bioinspired, Biomimetic and Nanobiomaterials. 2018; 7(2): 90
[Pubmed] | [DOI]
2 Optimization of a novel in situ gel for sustained ocular drug delivery using Box-Behnken Design: In vitro, ex vivo, in vivo and human studies
Ketan M. Ranch,Furqan A. Maulvi,Mausam J. Naik,Akshay R. Koli,Rajesh K. Parikh,Dinesh O. Shah
International Journal of Pharmaceutics. 2018;
[Pubmed] | [DOI]
3 Improving therapeutic efficacy of voriconazole against fungal keratitis: Thermo-sensitive in situ gels as ophthalmic drug carriers
Neslihan Üstündag Okur,Vildan Yozgatli,Mehmet Evren Okur,Aysegül Yoltas,Panoraia I. Siafaka
Journal of Drug Delivery Science and Technology. 2018;
[Pubmed] | [DOI]
4 Biopolymer-based strategies in the design of smart medical devices and artificial organs
Lina Altomare,Lorenzo Bonetti,Chiara E Campiglio,Luigi De Nardo,Lorenza Draghi,Francesca Tana,Silvia Farè
The International Journal of Artificial Organs. 2018; 41(6): 337
[Pubmed] | [DOI]
5 Ophthalmic Drug Delivery Systems for Antibiotherapy—A Review
Marion Dubald,Sandrine Bourgeois,Véronique Andrieu,Hatem Fessi
Pharmaceutics. 2018; 10(1): 10
[Pubmed] | [DOI]
6 Investigation of effectiveness of some extensively used polymers on thermoreversible properties of Pluronic ® tri-block copolymers
Nilesh R. Rarokar,Suprit D. Saoji,Pramod B. Khedekar
Journal of Drug Delivery Science and Technology. 2018; 44: 220
[Pubmed] | [DOI]
7 In Situ Gel Formulation for Enhanced Ocular Delivery of Nepafenac
Haley Shelley,Roxanne M. Rodriguez-Galarza,Sue H. Duran,Eva M. Abarca,R. Jayachandra Babu
Journal of Pharmaceutical Sciences. 2018;
[Pubmed] | [DOI]
8 Ophthalmic gels: Past, present and future
Ali A. Al-Kinani,Ghada Zidan,Naba Elsaid,Ali Seyfoddin,Adam W.G. Alani,Raid G. Alany
Advanced Drug Delivery Reviews. 2017;
[Pubmed] | [DOI]
9 Preparation and evaluation of novel chitosan: gelrite ocular system containing besifloxacin for topical treatment of bacterial conjunctivitis: scintigraphy, ocular irritation and retention assessment
Syed Sarim Imam,Syed Nasir Abbas Bukhari,Asgar Ali
Artificial Cells, Nanomedicine, and Biotechnology. 2017; : 1
[Pubmed] | [DOI]
10 Approaches in topical ocular drug delivery and developments in the use of contact lenses as drug-delivery devices
Prina Mehta,Rita Haj-Ahmad,Ali Al-Kinani,Muhammad Sohail Arshad,Ming-Wei Chang,Raid G Alany,Zeeshan Ahmad
Therapeutic Delivery. 2017; 8(7): 521
[Pubmed] | [DOI]
11 Emerging strategies for antimicrobial drug delivery to the ocular surface: Implications for infectious keratitis
Ajay Sharma,Jonathan Taniguchi
The Ocular Surface. 2017;
[Pubmed] | [DOI]
12 Non-invasive strategies for targeting the posterior segment of eye
Asadullah Madni,Muhammad Abdur Rahem,Nayab Tahir,Muhammad Sarfraz,Abdul Jabar,Mubashar Rehman,Prince Muhammad Kashif,Syed Faisal Badshah,Kifayat Ullah Khan,Hélder A. Santos
International Journal of Pharmaceutics. 2017; 530(1-2): 326
[Pubmed] | [DOI]
13 In Vitro Evaluation of the Drug Reservoir Function of Human Amniotic Membrane Using Moxifloxacin as a Model Drug
Madhavi Latha Yelchuri,Bhagyashree Madhavi,Nilam Gohil,Hitha Sara Sajeev,Namperumalsamy Venkatesh Prajna,Senthilkumari Srinivasan
Cornea. 2017; 36(5): 594
[Pubmed] | [DOI]
14 In vitro and in vivo evaluation of in situ gelling systems for sustained topical ophthalmic delivery: state of the art and beyond
Pierre-Louis Destruel,Ni Zeng,Marc Maury,Nathalie Mignet,Vincent Boudy
Drug Discovery Today. 2016;
[Pubmed] | [DOI]
15 Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride
S.B. Makwana,V.A. Patel,S.J. Parmar
Results in Pharma Sciences. 2016; 6: 1
[Pubmed] | [DOI]
16 Modern approaches to the ocular delivery of cyclosporine A
Priyanka Agarwal,Ilva D. Rupenthal
Drug Discovery Today. 2016;
[Pubmed] | [DOI]
17 LRP-1 Pathway Targeted Inhibition of Vascular Abnormalities in the Retina of Diabetic Mice
Ahamed Hossain,Lamiya Tauhid,Ian Davenport,Thomas Huckaba,Richard Graves,Tarun Mandal,Syed Muniruzzaman,Syed A. Ahmed,Partha S. Bhattacharjee
Current Eye Research. 2016; : 1
[Pubmed] | [DOI]
18 Protective effects of bestatin in the retina of streptozotocin-induced diabetic mice
Ahamed Hossain,David Heron,Ian Davenport,Thomas Huckaba,Richard Graves,Tarun Mandal,Syed Muniruzzaman,Shusheng Wang,Partha S. Bhattacharjee
Experimental Eye Research. 2016;
[Pubmed] | [DOI]
19 Preparation, pharmacokinetics and pharmacodynamics of ophthalmic thermosensitive in situ hydrogel of betaxolol hydrochloride
Weiwei Huang,Nan Zhang,Haiying Hua,Tuanbing Liu,Yafang Tang,Lingling Fu,Yanan Yang,Xiujie Ma,Yongxing Zhao
Biomedicine & Pharmacotherapy. 2016; 83: 107
[Pubmed] | [DOI]
20 In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan
Anxo Fernández-Ferreiro,Miguel González Barcia,María Gil-Martínez,Alba Vieites-Prado,Isabel Lema,Barbara Argibay,José Blanco Méndez,Maria Jesus Lamas,Francisco Javier Otero-Espinar
European Journal of Pharmaceutics and Biopharmaceutics. 2015; 94: 342
[Pubmed] | [DOI]
21 Hydrogels in ophthalmic applications
Susanne Kirchhof,Achim M. Goepferich,Ferdinand P. Brandl
European Journal of Pharmaceutics and Biopharmaceutics. 2015; 95: 227
[Pubmed] | [DOI]
22 Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative Approach for the Controlled Delivery of Docetaxel
Nilesh R. Rarokar,Suprit D. Saoji,Nishikant A. Raut,Jayashree B. Taksande,Pramod B. Khedekar,Vivek S. Dave
AAPS PharmSciTech. 2015;
[Pubmed] | [DOI]
23 Aqueous Nanomicellar Formulation for Topical Delivery of Biotinylated Lipid Prodrug of Acyclovir: Formulation Development and Ocular Biocompatibility
Aswani Dutt Vadlapudi,Kishore Cholkar,Ramya Krishna Vadlapatla,Ashim K. Mitra
Journal of Ocular Pharmacology and Therapeutics. 2014; 30(1): 49
[Pubmed] | [DOI]
24 Topical delivery of ocular therapeutics: carrier systems and physical methods
Joel G. Souza,Karina Dias,Tatiana Aparecida Pereira,Daniela Spuri Bernardi,Renata F. V. Lopez
Journal of Pharmacy and Pharmacology. 2013; : n/a
[Pubmed] | [DOI]
25 Dual sustained release delivery system for multiple route therapy of an antiviral drug
D. Ramyadevi,P. Sandhya
Drug Delivery. 2013; : 1
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Materials and Me...
Results and Disc...
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded1188    
    Comments [Add]    
    Cited by others 25    

Recommend this journal