Pharmaceutics and Industrial Pharmacy, Cairo University Faculty of Pharmacy, Cairo, Egypt.
Quality Assurance Department, Sigma Tec Pharmaceutical Company, Giza, Egypt.
Drug Deliv. 2021 Dec;28(1):293-305. doi: 10.1080/10717544.2021.1872740.
The aim of this work is to survey the potential of cubogel as an ocular dosage form to boost the corneal permeability of Dorzolamide Hydrochloride DZ; an antiglaucomal drug. DZ-loaded cubosomal dispersions were prepared according to Box-Behnken design, where the effect of independent variables; Monoolein MO concentration (2.5, 5 and 7.5%w/w), Pluronic F127 concentration (0.25, 0.5 and 0.75%w/w) and magnetic stirrer speed of (400, 800 and 1200 rpm) was studied on PS (nm), Zp (-mV) and Q 2 h (%) respectively. The prepared formulae were characterized via drug content DC (%), particle size PS (nm), polydispersity index PDI, zeta potential Zp (-mV), drug release (Q 2 h%) and finally TEM. The optimized formulation composed of: 6.13% w/w of MO, 0.75% w/w of F127 and prepared at 1200 rpm stirring speed was chosen based on the criteria of minimum PS (nm), maximum Zp (-mV) and minimum Q 2 h (%). Results revealed that the optimum formula showed PS of 153.3 ± 8.4 n, Zp of 32 ± 3 -mV and 37.78 ± 1.3% released after 2 h. Carbopol 934 (1% w/v) as gelling agent was used to prepare the optimum cubogel, which was further evaluated by DSC, permeation and stability studies at 4 °C for three months. Moreover, studies of the optimized cubogel include; draize test, histological examination, confocal laser scanning microscopy (CLSM) and intraocular pressure (IOP) measurement. Results revealed that the optimized cubogel was considerably safe, stable and competent to corneal delivery as assured by draize and histological examination. CLSM showed a deeper penetration of more than 2.5-fold. A higher bioavailability (288.24 mg. h/ml) was attained from cubogel compared to the market product Trusopt eye drops (115.40 mg. h/ml) following IOP measurement. Therefore, DZ-loaded cubogel could be considered as promising delivery system to boost the transcorneal permeation hence corneal bioavailability of DZ as antiglaucomal drug.
本工作旨在考察 Cubogel 作为眼部剂型的潜力，以提高多佐胺盐酸盐（DZ）作为抗青光眼药物的角膜透过性。根据 Box-Behnken 设计，制备载多佐胺 Cubosomal 分散体，考察独立变量：单油酸甘油酯（MO）浓度（2.5、5 和 7.5%w/w）、泊洛沙姆 F127 浓度（0.25、0.5 和 0.75%w/w）和搅拌速度（400、800 和 1200 rpm）对 PS（nm）、Zp（-mV）和 Q 2h（%）的影响。通过药物含量 DC（%）、粒径 PS（nm）、多分散指数 PDI、Zeta 电位 Zp（-mV）、药物释放（Q 2h%）和 TEM 对制备的配方进行了表征。根据 PS（nm）最小、Zp（-mV）最大和 Q 2h（%）最小的标准，选择由 6.13%w/w MO、0.75%w/w F127 和 1200 rpm 搅拌速度组成的最佳配方。结果表明，最佳配方的 PS 为 153.3±8.4nm、Zp 为 32±3-mV、2h 后释放 37.78±1.3%。将卡波姆 934（1%w/v）用作胶凝剂，制备最佳 Cubogel，并在 4°C 下进行 3 个月的 DSC、渗透和稳定性研究。此外，对优化后的 Cubogel 进行了研究，包括：Draize 试验、组织学检查、共焦激光扫描显微镜（CLSM）和眼压（IOP）测量。结果表明，优化后的 Cubogel 通过 Draize 和组织学检查被认为是安全、稳定和有能力进行角膜给药的。CLSM 显示穿透深度增加了 2.5 倍以上。通过 IOP 测量，与市售产品 Trusopt 滴眼剂（115.40mg.h/ml）相比，Cubogel 可获得更高的生物利用度（288.24mg.h/ml）。因此，载多佐胺 Cubogel 可作为一种有前途的给药系统，以提高多佐胺盐酸盐的跨角膜渗透，从而提高其作为抗青光眼药物的角膜生物利用度。
