formulation and stability of an extemporaneous 0.02% chlorhexidine digluconate ophthalmic solution

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ID: 155274
2015
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Abstract
Acanthamoeba keratitis is difficult to treat because Acanthamoeba cysts are resistant to the majority of antimicrobial agents. Despite the efficacy of 0.02% chlorhexidine in treating Acanthamoeba keratitis, a lack of data in the literature regarding the formulation's stability limits its clinical use. The objective of this study was to develop an optimal extemporaneous 0.02% chlorhexidine digluconate ophthalmic formulation for patients in need. Methods: With available active pharmaceutical ingredients, 0.02% chlorhexidine digluconate sample solutions were prepared by diluting with BSS Plus Solution or acetate buffer. Influences of the buffer, type of container, and temperature under daily-open condition were assessed based on the changes of pH values and chlorhexidine concentrations of the test samples weekly. To determine the beyond-use date, the optimal samples were stored at 2–8°C or room temperature, and analyzed at time 0 and at Week 1, Week 2, Week 3, Week 4, Week 5, Week 8, Week 12, and Week 24. Results: Despite chlorhexidine exhibiting better stability in acetate buffer than in BSS solution, its shelf-life was < 14 days when stored in a light-resistant low-density polyethylene container. The acetate-buffered 0.02% chlorhexidine digluconate solution stored in light-resistant high-density polyethylene eyedroppers did not exhibit significant changes in pH or strength at any time interval. Conclusion: The acetate-buffered 0.02% chlorhexidine digluconate ophthalmic solution stored in light-resistant high-density polyethylene eyedroppers demonstrated excellent stability at 2–25°C for 6 months after being sealed and for 1 month after opening. This finding will enable us to prepare 0.02% chlorhexidine digluconate ophthalmic solutions based on a doctor's prescription.
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Authors ;Shu-Chiao Lin;Chih-Fen Huang;Li-Jiuan Shen;Hsueh-Ju Wang;Chia-Yu Lin;Fe-Lin Lin Wu
Journal Bioorganic & medicinal chemistry letters
Year 2015
DOI
10.1016/j.jfma.2014.08.003
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