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Published on: September 17, 2014
Polystyrene Sulfonate Resin as an Ophthalmic Carrier for Enhanced Bioavailability of Ligustrazine Phosphate
Liyun Dong1, Hui Zhang1, Guoqing Zhang2
1College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Yangtze Delta Drug Advanced Research Institute, Nantong 226133, China; Jiangsu Yunshi Pharmaceutical Technology Co.Ltd., Nantong 226133, China.
Abstract:
Topical ocular sustained-release drug delivery systems represent an effective strategy for the treatment of ocular diseases, for which a suitable carrier has yet to be sufficiently developed. Herein, an eye-compatible sodium polystyrene sulfonate resin (SPSR) was synthesized with a uniform particle size of about 3 μm. Ligustrazine phosphate (LP) was adsorbed to SPSR by cation exchange to form LP@SPSR. LP@SPSR suspension eye drops were further developed using the combination of Carbopol 934P and xanthan gum as suspending agents. The LP@SPSR suspension showed a sustained release in vitro, which was consistent with the observed porcine corneal penetration ex vivo. Pharmacokinetics in tear fluid of rabits indicated that LP@SPSR suspension led to prolonged ocular retention of LP and a 2-fold improved the area under the drug concentration-time curve (AUC0-t). Pharmacokinetics in the aqueous humor of rabbits showed 2.8-fold enhancement in the AUC0-t compared to LP solution. The LP@SPSR suspension exhibited no cytotoxicity to human corneal epithelial cells, nor irritation was observed in rabbit eyes. Thus, the LP@SPSR suspension has been validated as a safe and sustained release system leading to enhanced ophthalmic bioavailability for treating ocular diseases.
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