IN VITRO ENTRAPMENT AND RELEASE STUDIES OF LEVOFLOXACIN USING EPICHLOROHYDRIN-CROSSLINKED HYDROGEL
DOI:
https://doi.org/10.22159/ijap.2019.v11s5.T0107Keywords:
Cross-linked hydrogel, Levofloxacin, Ophthalmic preparationAbstract
Objective: This study aimed to optimize and evaluate the controlled release rate, ocular irritancy, and in vitro antimicrobial properties of levofloxacin
entrapped in the epichlorohydrin-crosslinked hydrogel of sodium carboxymethyl cellulose (NaCMC) and gelatin.
Materials and Methods: Various parameters such as polymer ratio, amount of crosslinker, temperature, reaction time, swelling capacity, and percent
drug loading were considered in Optimized levofloxacin hydrogel. Hydrogel preparations with higher amount of drug loaded were further analyzed
to determine its in vitro drug release rate, ocular irritancy on New Zealand rabbits, and antimicrobial activities against Pseudomonas aeruginosa
and Staphylococcus aureus. Optimized levofloxacin hydrogel (OLH) was then subjected to 3-month stability testing at 40 ± 2°C and 75 ± 5% relative
humidity in which samples were withdrawn at the end of each month for analysis.
Results: Polymer groups with higher concentrations of NaCMC have higher swelling and drug loading capacities than those with higher gelatin
concentrations. Meanwhile, qualitative analysis using differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning
electron microscopy verified the presence of levofloxacin in the epichlorohydrin-cross-linked hydrogel. Among the four polymer ratio, F3 was the
optimized hydrogel with drug-loaded concentration of 99.50%, which was within the acceptable assay limit of 0.5% levofloxacin solution based on
United States Pharmacopeia monograph. It followed the Higuchi kinetic model with a drug release mechanism of super case 2 transport indicating
hydrogel swelling as a key factor for its controlled drug release. In vitro, antibacterial test against P. aeruginosa and S. aureus was sensitive to optimized
levofloxacin hydrogel (OLH) with inhibitory diameter zones of 31.68 and 37.05 mm, respectively. Ocular irritancy test also showed that the OLH is
non-irritating on installation in the cul-de-sac of New Zealand rabbits.
Conclusion: Optimized levofloxacin hydrogel was effective, non-irritating, and stable, which can be used as an alternative to conventional 0.5%
levofloxacin ophthalmic solution.
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References
Drechslera spp. treated with voriconazole: A case report. Case Rep
Ophthalmol Med 2013;2013:626704.
2. Al-Mujaini A, Al-Kharusi N, Thakral A, Wali UK. Bacterial keratitis:
Perspective on epidemiology, clinico-pathogenesis, diagnosis and
treatment. Sultan Qaboos Univ Med J 2009;9:184-95.
3. Sharma S. Antibiotic resistance in ocular bacterial pathogens. Indian J
Med Microbiol 2011;29:218-22.
4. Alves DA, Machado D, Melo A, Pereira RF, Severino P,
de Hollanda LM. Preparation of thermosensitive gel for controlled
release of levofloxacin and their application in the treatment of
multidrug-resistant bacteria. Biomed Res Int 2016;2016:9702129.
5. Maitra J, Shukla VK. Cross-linking in hydrogels – A review. Am J
Polym Sci 2014;4:25-31.
6. Wong RS, Ashton M, Dodou K. Effect of crosslinking agent
concentration on the properties of unmedicated hydrogels.
Pharmaceutics 2015;7:305-19.
7. Mandal S, Thimmasetty MK, Prabhushankar G, Geetha M. Formulation
and evaluation of an in situ gel-forming ophthalmic formulation of
moxifloxacin hydrochloride. Int J Pharm Investig 2012;2:78-82.
8. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on
drug release from controlled drug delivery systems. Acta Pol Pharm
2010;67:217-23.
9. Tulain UR, Ahmad M, Rashid A, Iqbal FM. Development and
characterization of smart drug delivery system. Acta Pol Pharm
2016;73:1009-22.
10. Hoosain FG, Choonara YE, Kumar P, Tomar LK, Tyagi C, du Toit LC,
et al. An epichlorohydrin-crosslinked semi-interpenetrating GG-PEO
network as a xerogel matrix for sustained release of sulpiride. AAPS
PharmSciTech 2014;15:1292-306.
11. Kodre KV, Attarde SR, Yendhe PR, Patil RY, Barge VU.
Differential scanning calorimetry: A review. Res Rev J Pharm Anal
2014;3:11-22.
12. Buhus G, Peptu C, Popa M, Desbrieres J. Controlled release of
water soluble antibiotics carboxymethylcellulose- and gelatin-based
hydrogels crosslinked with epichlorohydrin. Cell Chem Technol
2009;43:141-51.
13. Buhus G, Popa M, Desbrieres J. Hydrogels based on
carboxymethylcellulose and gelatin for inclusion and release of
chloramphenicol. J Bioact Compat Pol 2009;24:525-45.
14. Ahmad I, Bano R, Sheraz MA, Ahmed S, Mirza T, Ansari SA.
Photodegradation of levofloxacin in aqueous and organic solvents:
A kinetic study. Acta Pharm 2013;63:223-9.
15. Jahit IS, Nazmi NN, Isa MI, Sarbon NM. Preparation and physical
properties of gelatin/CMC/chitosan composite films as affected by
drying temperature. Int Food Res J 2016;23:1068-74.
16. Ranjbar M, Azizi MH, Hashtjin AM. Evaluation of physico-mechanical
and antimicrobial properties of gelatin-carboxymethyl cellulose film
containing essential oil of bane (Pistacia atlantica). Nutr Food Sci Res
2017;4:11-7.
17. Hirschl C, Biebl-Rydlo M, DeBiasio M, Muhleisen W, Neumaier L,
Scherf W, et al. Determining the degree of crosslinking of ethylene
vinyl acetate photovoltaic module encapsulants – A comparative study.
Sol Energy Mater Sol Cells 2013;116:203-18.
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