Teaima Mahmoud H, Mohamed Mohamed Azmi Ahmed, Abd El Rehem Randa Tag, Tayel Saadia A, El-Nabarawi Mohamed A, Fouad Shahinaze A
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Obour Pharmaceutical Industries, Cairo 13024, Egypt.
Pharmaceutics. 2021 May 10;13(5):682. doi: 10.3390/pharmaceutics13050682.
Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels. The synergistic effect of permeation enhancers and iontophoresis was investigated via both ex vivo and in vivo permeation studies. Ex vivo iontophoretic permeation studies were performed by using male albino Wistar rat skin. Cellosolve hydrogel (F7) showed a 1.5-fold increase in Q, Jss, and FER compared to F5 (lacking permeation enhancer). BH pharmacokinetic data were studied in human volunteers, following transdermal delivery of F7, using Phoresor Unit II iontophoresis device, compared to conventional oral tablets. F7 showed 1.9- and 2-fold higher values of C and AUC, respectively compared to Concor tablets, as well as a smaller T (2.00 ± 2.00 h). The relative bioavailability of F7 was found to be 201.44%, relative to Concor tablets, demonstrating the significantly enhanced transdermal permeation of BH from the selected hydrogel by iontophoresis, in human volunteers. Finally, results showed the successful utility of permeation enhancers combined with iontophoresis in significantly enhanced transdermal permeation of BH, despite its large molecular weight and hydrophilic nature. Therefore, this strategy could be employed as a successful alternative route of administration to conventional oral tablets.
富马酸比索洛尔（BH）是一种抗高血压药物，用作慢性高血压和心绞痛的一线治疗药物。我们的研究旨在通过不同制备的水凝胶增强BH（一种高分子量的亲水性活性药物）的透皮递送。通过体外和体内渗透研究考察了渗透促进剂和离子导入的协同作用。体外离子导入渗透研究采用雄性白化Wistar大鼠皮肤进行。与F5（不含渗透促进剂）相比，溶纤剂水凝胶（F7）的Q、Jss和FER增加了1.5倍。在人类志愿者中，使用Phoresor Unit II离子导入装置经皮递送F7后，研究了BH的药代动力学数据，并与传统口服片剂进行比较。与康可片剂相比，F7的C和AUC值分别高出1.9倍和2倍，且T更小（2.00±2.00小时）。相对于康可片剂，F7的相对生物利用度为201.44%，表明在人类志愿者中，离子导入可显著增强BH从所选水凝胶中的透皮渗透。最后，结果表明，尽管BH分子量较大且具有亲水性，但渗透促进剂与离子导入相结合在显著增强BH透皮渗透方面具有成功的实用性。因此，该策略可作为传统口服片剂的一种成功替代给药途径。
