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

Chen Chen,Ma Ma,Tu Tu,Yin Yin,Shen Shen

doi:10.3390/pharmaceutics11040183

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.

Highlights

The prevalence of conjunctivitis, especially those caused by Chlamydia trachomatis remains very high
It has been reported by World Health Organization (WHO) that there are approximately 300–500 million people who had suffered from trachoma [1]
It is commonly recognized that solubility and stability properties of active pharmaceutical ingredients (APIs) are the major contributing factors for a formulation

Summary

Introduction

The prevalence of conjunctivitis, especially those caused by Chlamydia trachomatis remains very high. It has been reported by World Health Organization (WHO) that there are approximately 300–500 million people who had suffered from trachoma [1]. At least 1.0 g of AZI was required for each oral dose to ensure the sufficient concentration of AZI in aqueous humor, tears and conjunctiva coat to exert its inhibitory effects. A topical ophthalmic formulation of AZI with advantages of lower dose frequency, more convenience and better compliance is required, which may facilitate the reduction of the risk of selecting resistant bacteria [8]. To maintain the effective drug concentration in the tear film, more frequent instillations were required, which might cause side effects and result in poor patient compliance [11]

Methods

Results

Conclusion