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. 2019 Apr 15;11(4):183.
doi: 10.3390/pharmaceutics11040183.

Preparation and Evaluation of Topically Applied Azithromycin Based on Sodium Hyaluronate in Treatment of Conjunctivitis

Qian Chen  1   2 , Chun Yin  3   4 , Jiang Ma  5 , Jiasheng Tu  6   7 , Yan Shen  8   9
Affiliations

Preparation and Evaluation of Topically Applied Azithromycin Based on Sodium Hyaluronate in Treatment of Conjunctivitis

Qian Chen et al. Pharmaceutics. .

Abstract

Azithromycin (AZI) eye drops containing sodium hyaluronate (SH) were developed to improve the bioavailability of AZI. Interaction between AZI and SH in the AZI-SH formulation was investigated by differential scanning calorimetry, X-ray diffraction, and ¹H-nuclear magnetic resonance spectroscopy analyses. Moreover, advantages of using SH as an excipient were investigated by comparing physiological properties and pharmacokinetic behaviors of SH-containing AZI eye drops with that of hydroxypropyl methylcellulose (HPMC)-containing formulation. In addition, safety of the developed AZI-SH eye drops was evaluated by in vitro 3-(4,5-dimethyl-2-Thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide assay (MTT assay) and neutral red uptake assay as well as in vivo eye irritation test and acute toxicity test. The results indicated that AZI formed a complex with SH under a slightly acidic condition. The area under the curve (AUC) of AZI in SH-containing formulation was 1.58-fold higher (P<0.01) than that in HPMC-containing formulation due to the interaction between the amine group of AZI and the carboxyl group of SH, despite of the higher viscosity of HPMC-containing formulation. Safety evaluation showed that AZI-SH eye drops caused no obvious eye irritation and acute toxicity. In conclusion, the developed SH-containing AZI formulation possessing advantages of longer retention time and higher drug availability was a promising drug formulation for topical ocular therapy.

Keywords: azithromycin; bioadhesion; eye drops; ocular bioavailability; safety evaluation; sodium hyaluronate.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Degradation kinetics of azithromycin. A: Apparent first-order plot of azithromycin (AZI) hydrolysis at various pH values. Temperature was 75 °C and ionic strength (I) = 0.3. B: the hydrolysis of AZI at various pH, 75 °C and I = 0.3.
Figure 2
Figure 2
Illustration of interaction between AZI and sodium hyaluronate (SH). A: Differential Scanning Calorimetry (DSC) thermograms; B: X-ray diffraction (XRD) patterns; C: 1H-Nuclear Magnetic Resonance (1H-NMR) spectra. (a) AZI, (b) SH, (c) physical mixture of AZI+SH and (d) AZI-SH complex. D: structure of sodium hyaluronate and azithromycin.
Figure 3
Figure 3
Comparison of the viscosity between AZI-SH formulation, AZI-HPMC formulation, blank SH and blank HPMC.
Figure 4
Figure 4
Concentration-time profiles of AZI in tear fluid after instillation of HPMC preparation and SH preparation in conscious rabbits (n = 5).
Figure 5
Figure 5
Cell viability against 3T3-L1 cells determined by MTT assay (A) and Neutral red uptake (NRU) assay (B). (** P < 0.01).
Figure 6
Figure 6
Evaluation of eye irritation by histopathological examinations of iris, cornea, conjunctiva and sclera.
See this image and copyright information in PMC

References

    1. Taylor H.R. Trachoma—The future for a disease of the past. Br. J. Ophthalmol. 1993;77:66. doi: 10.1136/bjo.77.2.66. - DOI - PMC - PubMed
    1. Tung N.T., Tran C.S., Nguyen T.L., Hoang T., Trinh T.D., Nguyen T.N. Formulation and biopharmaceutical evaluation of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets. Eur. J. Pharm. Biopharm. 2017 doi: 10.1016/j.ejpb.2017.03.017. - DOI - PubMed
    1. Liu F., Porco T.C., Mkocha H.A., Muñoz B., Ray K.J., Bailey R.L., Lietman T.M., West S.K. The efficacy of oral azithromycin in clearing ocular chlamydia: Mathematical modeling from a community-randomized trachoma trial. Epidemics. 2014;6:10–17. doi: 10.1016/j.epidem.2013.12.001. - DOI - PMC - PubMed
    1. Mohammadpour M., Abrishami M., Masoumi A., Hashemi H. Trachoma: Past, present and future. J. Curr. Ophthalmol. 2016;28:165–169. doi: 10.1016/j.joco.2016.08.011. - DOI - PMC - PubMed
    1. Schachter J., West S.K., Mabey D., Dawson C.R., Bobo L., Bailey R., Vitale S., Quinn T.C., Sheta A., Sallam S. Azithromycin in control of trachoma. Lancet. 1999;354:630–635. doi: 10.1016/S0140-6736(98)12387-5. - DOI - PubMed

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