Elsayed Mahmoud M A, Aboelez Moustafa O, Mohamed Mohamed S, Mahmoud Reda A, El-Shenawy Ahmed A, Mahmoud Essam A, Al-Karmalawy Ahmed A, Santali Eman Y, Alshehri Sameer, Elsadek Mahmoud Elkot Mostafa, El Hamd Mohamed A, Ramadan Abd El Hakim
Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt.
Pharmaceutics. 2022 Aug 4;14(8):1629. doi: 10.3390/pharmaceutics14081629.
Hyperlipidemia is still the leading cause of heart disease in patients with hypertension. The purpose of this study is to make rosuvastatin calcium (ROS) and atenolol (AT) bilayer tablets to treat coexisting dyslipidemia and hypertension with a single product. ROS was chosen for the immediate-release layer of the constructed tablets, whereas AT was chosen for the sustained-release layer. The solid dispersion of ROS with sorbitol (1:3 /) was utilized in the immediate-release layer while hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC), and sodium bicarbonate were incorporated into the floating sustained-release layer. The concentrations of HPMC and EC were optimized by employing 3 full factorial designs to sustain AT release. The bilayer tablets were prepared by the direct compression method. The immediate-release layer revealed that 92.34 ± 2.27% of ROS was released within 60 min at a pH of 1.2. The second sustained-release layer of the bilayer tablets exhibited delayed release of AT (96.65 ± 3.36% within 12 h) under the same conditions. The release of ROS and AT from the prepared tablets was found to obey the non-Fickian diffusion and mixed models (zero-order, Higuchi and Korsmeyer-Peppas), respectively. Preclinical studies using rabbit models investigated the impact of ROS/AT tablets on lipid profiles and blood pressure. A high-fat diet was used to induce obesity in rabbits. Bilayer ROS/AT tablets had a remarkable effect on decreasing the lipid profiles, slowing weight gain, and lowering blood pressure to normal levels when compared to the control group.
高脂血症仍然是高血压患者心脏病的主要病因。本研究的目的是制备瑞舒伐他汀钙（ROS）和阿替洛尔（AT）双层片，用单一产品治疗并存的血脂异常和高血压。在制备的片剂中，ROS被选作速释层，而AT被选作缓释层。速释层使用了ROS与山梨醇（1:3）的固体分散体，而羟丙基甲基纤维素（HPMC）、乙基纤维素（EC）和碳酸氢钠被加入到漂浮缓释层中。通过采用3因素全因子设计优化HPMC和EC的浓度以维持AT的释放。双层片采用直接压片法制备。速释层显示，在pH值为1.2时，60分钟内ROS的释放率为92.34±2.27%。在相同条件下，双层片的第二层缓释层显示AT的延迟释放（12小时内为96.65±3.36%）。发现所制备片剂中ROS和AT的释放分别符合非Fickian扩散模型和混合模型（零级、Higuchi模型和Korsmeyer-Peppas模型）。使用兔模型的临床前研究调查了ROS/AT片对血脂谱和血压的影响。采用高脂饮食诱导兔肥胖。与对照组相比，双层ROS/AT片在降低血脂谱、减缓体重增加以及将血压降至正常水平方面具有显著效果。
