## 1 Introduction  
Hypertension is affecting one billion people and is the most common modifiable risk factor for cardiovascular disease (CVD) [1, 2]. Hyperlipidemia, characterized by abnormal blood lipid levels, is also recognized as one of the important risk factors of CVD [3, 4]. Hypertension and hyperlipidemia frequently coexist and are associated with elevated cardiovascular adverse outcomes [5]. Globally, CVD is the primary cause of mortality [6]. It is estimated that 7.8 million people will die prematurely from CVD by 2025 [7]. Despite their increasing prevalence, the proportions of hypertension and hyperlipidemia awareness, treatment, and control are low [8, 9]. The trial has demonstrated that lowering lipid levels and blood pressure decreases the incidence of major cardiovascular events more effectively than regulating hypertension or hypercholesterolemia separately [10]. Therefore, significant joint control of blood pressure and blood lipids is needed for reducing the mortality rate of CVD. Captopril (CAP), an orally active angiotensin-converting enzyme inhibitor (ACEI), is considered the preferred drug for antihypertensive treatment due to its effectiveness and low toxicity. Simvastatin (SIM) is a hydroxymethyl glutamate coenzyme A (HMG-CoA) reductase inhibitor that reduces total cholesterol and low-density lipoprotein cholesterol, thereby reducing the risk of atherosclerosis and CVD [11]. CAP and SIM have profitable effects beyond blood pressure and lipid lowering, and when combined, they achieve greater improvements in outcomes than those associated with either monotherapies [12]. However, when administered orally, CAP undergoes first-pass hepatic metabolism [13; 14], its bioavailability is reduced to 55% in the presence of food, and its half-life is less than 2 h [15]. SIM also has a significant liver first-pass effect, low bioavailability of only 5%, and a short half-life of 2 h [16]. So, oral SIM and CAP both have common shortcomings, including significant liver first-pass effects, low bioavailability, and a short half-life. The transdermal drug delivery system (TDDS) is one of the systems under the controlled drug delivery category that aims to deliver drugs through the skin at a predetermined and controlled rate [17]. The TDDS has undergone the development of three generations [18]. The first generation includes ointments, creams, sprays, gels, or patches [18]. The second generation is involved in the use of different enhancements, including chemical enhancement, iontophoresis, and non-cavitational ultrasound [19; 20]. The third generation correlates with novel chemical enhancers, electroporation, microdermabrasion, thermal ablation, cavitational ultrasound, and microneedle-based delivery [20; 21]. Based on the above statements, the three generations of the TDDS all apply transdermal enhancer technology, known as physical enhancers or chemical enhancers. However, most physical enhancers rely on relatively costly, reusable devices [20], and some physical enhancers, such as microneedles, have physical invasiveness, which raises additional safety and sterility concerns [20]. Various chemical enhancers can be integrated into small, inexpensive patches that patients find convenient [20]. Thus, chemical enhancers may have some advantage in the transdermal drug delivery system. In 1979, the US Food and Drug Administration (FDA) approved the first transdermal patch (scopolamine transdermal patch) to prevent motion sickness [22; 23]. Since then, many transdermal patches have been approved for the market, including Estradiol; Testosterone; Clonidine; Fentanyl; Nitroglycerin; Nicotine transdermal patches; and so on [23]. The clonidine TDDS is used for the treatment of hypertension [24]; it can improve compliance and patient acceptance in antihypertensive treatment, which may enhance the clinical treatment advantages [25].