Department of Pharmaceutics and Industrial Pharmacy, Beni-Suef University, Beni-Suef, 62511, Egypt.
Department of Pharmaceutics and Clinical Pharmacy, Nahda University, Beni-Suef, Egypt.
Drug Deliv Transl Res. 2018 Feb;8(1):165-177. doi: 10.1007/s13346-017-0449-5.
The aim of this study was to develop and optimize a betahistine dihydrochloride (BH) thermoreversible bioadhesive gel intended for transdermal delivery. The gels were obtained via cold method. A full factorial design was employed to investigate the joint effect of Poloxamer 407 concentration (18 and 20%), adhesive polymer type (Polyvinyl pyrolidone, Hydroxypropyl methylcellulose, and Carbopol 934), and adhesive polymer concentration (0.5 and 1.5%) on gelling temperature, viscosity at 37 °C, and adhesion strength. Data collected were analyzed using multiple linear regression. A desirability index approach with relative importance weight was used to choose the most desirable formulation. F4 (20% Poloxamer+1.5% Carbopol) was selected for further characterization. F4 released 96.97% drug in 12 h across hairless rat skin. F4 gelation temperature and time were 36 ± 0.35 °C, and 6 ± 0.7 min, respectively. F4 adhesive force was 8835.68 dyne/cm. F4 was tested for its appetite suppressing effect in a rat model and it was evaluated histopathologically. Rats' chow intake and weight gain was significantly decreased with no signs of inflammation or lipolysis when the optimized BH gel formulation, F4, was compared with untreated animals and animals treated with BH free gel. The results suggest that BH is percutaneously absorbed from the gel base and that the BH gel is tolerable. The desirability index approach with relative importance weight of responses was effective in determination of the optimum formulation. BH is systemically effective and well-tolerated when applied topically in hydrogel-based systems. The Carbopol-Poloxamer gel is a promising modality for transdermal delivery of BH.
本研究旨在开发和优化一种盐酸倍他司汀（BH）热可逆生物粘附凝胶，用于经皮给药。凝胶通过冷法获得。采用完全析因设计研究泊洛沙姆 407 浓度（18%和 20%）、粘附聚合物类型（聚乙烯吡咯烷酮、羟丙基甲基纤维素和卡波姆 934）和粘附聚合物浓度（0.5%和 1.5%）对胶凝温度、37°C 时的粘度和粘附强度的联合影响。收集的数据使用多元线性回归进行分析。采用具有相对重要性权重的理想指数方法选择最理想的配方。选择 F4（20%泊洛沙姆+1.5%卡波姆）进行进一步表征。F4 在 12 小时内通过无毛大鼠皮肤释放 96.97%的药物。F4 的凝胶化温度和时间分别为 36±0.35°C 和 6±0.7 分钟。F4 的粘附力为 8835.68 达因/厘米。F4 用于抑制大鼠食欲的作用模型测试，并进行组织病理学评估。与未处理动物和未用 BH 处理的凝胶处理动物相比，优化后的 BH 凝胶制剂 F4 可显著降低大鼠的饲料摄入量和体重增加，且无炎症或脂肪分解迹象。结果表明，BH 可从凝胶基质经皮吸收，且 BH 凝胶具有良好的耐受性。响应的理想指数方法与相对重要性权重相结合，可有效确定最佳配方。当以水凝胶为基础的系统局部应用时，BH 具有系统有效性且耐受性良好。卡波姆-泊洛沙姆凝胶是 BH 经皮给药的一种有前途的方式。
