Badr-Eldin Shaimaa M, Ahmed Osamaa Aa
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt.
Drug Des Devel Ther. 2016 Apr 5;10:1323-33. doi: 10.2147/DDDT.S103122. eCollection 2016.
Sildenafil citrate (SLD) is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor used for the oral treatment of erectile dysfunction and, more recently, for other indications, including pulmonary hypertension. The challenges facing the oral administration of the drug include poor bioavailability and short duration of action that requires frequent administration. Thus, the objective of this work is to formulate optimized SLD nano-transfersomal transdermal films with enhanced and controlled permeation aiming at surmounting the previously mentioned challenges and hence improving the drug bioavailability. SLD nano-transfersomes were prepared using modified lipid hydration technique. Central composite design was applied for the optimization of SLD nano-transfersomes with minimized vesicular size. The independent variables studied were drug-to-phospholipid molar ratio, surfactant hydrophilic lipophilic balance, and hydration medium pH. The optimized SLD nano-transfersomes were developed and evaluated for vesicular size and morphology and then incorporated into hydroxypropyl methyl cellulose transdermal films. The optimized transfersomes were unilamellar and spherical in shape with vesicular size of 130 nm. The optimized SLD nano-transfersomal films exhibited enhanced ex vivo permeation parameters with controlled profile compared to SLD control films. Furthermore, enhanced bioavailability and extended absorption were demonstrated by SLD nano-transfersomal films as reflected by their significantly higher maximum plasma concentration (C max) and area under the curve and longer time to maxi mum plasma concentration (T max) compared to control films. These results highlighted the potentiality of optimized SLD nano-transfersomal films to enhance the transdermal permeation and the bioavailability of the drug with the possible consequence of reducing the dose and administration frequency.
枸橼酸西地那非（SLD）是一种选择性环磷酸鸟苷特异性5型磷酸二酯酶抑制剂，用于口服治疗勃起功能障碍，最近也用于其他适应症，包括肺动脉高压。口服该药物面临的挑战包括生物利用度差和作用持续时间短，需要频繁给药。因此，这项工作的目的是制备优化的SLD纳米传递体透皮膜，以增强和控制药物渗透，旨在克服上述挑战，从而提高药物的生物利用度。采用改良的脂质水化技术制备了SLD纳米传递体。应用中心复合设计优化SLD纳米传递体，使其囊泡尺寸最小化。研究的自变量为药物与磷脂的摩尔比、表面活性剂亲水亲油平衡和水化介质pH值。制备了优化的SLD纳米传递体，并对其囊泡大小和形态进行了评估，然后将其掺入羟丙基甲基纤维素透皮膜中。优化后的传递体为单层球形，囊泡大小为130nm。与SLD对照膜相比，优化后的SLD纳米传递体膜表现出增强的体外渗透参数和可控的渗透曲线。此外，SLD纳米传递体膜显示出生物利用度提高和吸收延长，这体现在与对照膜相比，它们的最大血浆浓度（C max）和曲线下面积显著更高，达到最大血浆浓度的时间（T max）更长。这些结果突出了优化的SLD纳米传递体膜在增强药物透皮渗透和生物利用度方面的潜力，可能会降低剂量和给药频率。
