Al-Saedi Zahraa H F, Alzhrani Rami M, Boddu Sai H S
Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo Health Science Campus , Toledo, Ohio.
J Ocul Pharmacol Ther. 2016 Sep;32(7):451-62. doi: 10.1089/jop.2016.0013. Epub 2016 Jun 13.
The aim of this study was to develop and characterize a novel sustained-release drug delivery system of cyclosporine-A (CsA) using hydroxypropyl methylcellulose (HPMC) and xanthan gum (XG) for treating dry eye disease (DED).
Polymeric inserts of CsA were prepared using the solvent casting technique with a 2(3) full factorial design to evaluate the effect of HPMC and XG ratios and drug content on thickness, folding endurance, wettability, and in vitro drug release. Inserts were also evaluated for drug content, moisture absorption and loss, and surface pH. Inserts with an optimized ratio of HPMC and XG were sterilized with UV light and evaluated for morphology, thermal analysis, Fourier transform infrared spectroscopy, stability at 4°C, 25°C, and 40°C, cytotoxicity in cultured bovine corneal endothelial cells, and anti-inflammatory effect in Jurkat T cells.
The addition of XG increased the CsA release duration and enhanced the folding endurance of films. All films showed uniformity in drug content and thickness. Formulation F4 composed of 1% HPMC and 0.25% XG exhibited good folding endurance and sustained CsA release for up to 20 h. Sterility testing of F4 using plate and direct inoculation confirmed the formulation sterility and validated the sterilization method. The formulation was stable for at least 3 months at 4°C, 25°C, and 40°C. No cytotoxicity was observed in cultured bovine corneal endothelial cells for up to 24 h. The anti-inflammatory effect of CsA was intact in ophthalmic inserts.
In conclusion, combination therapy with HPMC and CsA can be a potential once-a-day formulation for treating DED.
本研究的目的是开发并表征一种新型的环孢素A（CsA）缓释给药系统，该系统使用羟丙基甲基纤维素（HPMC）和黄原胶（XG）来治疗干眼症（DED）。
采用溶剂浇铸技术，通过2（3）全因子设计制备CsA聚合物插入物，以评估HPMC和XG比例以及药物含量对厚度、耐折性、润湿性和体外药物释放的影响。还对插入物进行了药物含量、吸湿和失重以及表面pH值的评估。将具有优化的HPMC和XG比例的插入物用紫外线灭菌，并对其形态、热分析、傅里叶变换红外光谱、在4°C、25°C和40°C下的稳定性、在培养的牛角膜内皮细胞中的细胞毒性以及在Jurkat T细胞中的抗炎作用进行评估。
XG的加入延长了CsA的释放持续时间，并增强了薄膜的耐折性。所有薄膜的药物含量和厚度均表现出均匀性。由1% HPMC和0.25% XG组成的制剂F4具有良好的耐折性，CsA可持续释放长达20小时。使用平板法和直接接种法对F4进行的无菌测试证实了制剂的无菌性，并验证了灭菌方法。该制剂在4°C、25°C和40°C下至少3个月稳定。在培养的牛角膜内皮细胞中，长达24小时未观察到细胞毒性。CsA在眼科插入物中的抗炎作用保持完整。
总之，HPMC和CsA联合治疗可能是一种治疗DED的潜在每日一次制剂。
