Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza, Egypt.
Drug Des Devel Ther. 2021 Oct 7;15:4229-4242. doi: 10.2147/DDDT.S332729. eCollection 2021.
Statins are an important class of drugs that help to control hyperlipidemia, and one of these statins recently used is pitavastatin calcium (PITA). Nevertheless, the most reported adverse effect of statins is myopathy. Therefore, combining statins with non-steroidal anti-inflammatory drugs (NSAIDs) as Lornoxicam (LORNO) can help in the management of statin-induced myopathy.
This study aimed to formulate and evaluate different oral disintegrating tablets (ODTs) containing PITA using different co-processed excipients. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs. The pharmacokinetic parameters of PITA and LORNO in a single ODT were compared to those of the marketed products (Lipidalon and Lornoxicam).
Eight PITA-ODTs were prepared via direct compression. The prepared PITA-ODTs were evaluated for their weight variation, thickness, breaking force, friability, drug content, and wetting time (WT). In-vitro disintegration time (DT) and dissolution were also evaluated and taken as parameters for selection of the best formula based on the criteria of scoring the fastest DT and highest Q. LORNO was added to the selected PITA-ODT, forming a single ODT (M1) comprising both drugs, which was subjected to an in-vivo pharmacokinetic study using rats as an animal model and liquid chromatography-mass spectrometry (LC-MS/MS) for analysis of both drugs in rat plasma.
Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst (F2) had significantly (<0.05) the fastest DT (6.66±1.52 s) and highest Q (79.07±2.02%) and was chosen as the best formula. The in-vivo pharmacokinetic study of M1 formula showed higher percent relative bioavailability (%RB) of 286.7% and 169.73% for PITA and LORNO, respectively, compared with the marketed products.
The single ODT comprising PITA and LORNO was promising for instant co-delivery of both drugs with higher %RB when compared with the marketed products.
他汀类药物是一类重要的药物，有助于控制高血脂，其中一种他汀类药物最近使用的是匹伐他汀钙（PITA）。然而，他汀类药物最常见的不良反应是肌病。因此，将他汀类药物与非甾体抗炎药（NSAIDs）如氯诺昔康（LORNO）联合使用可以帮助治疗他汀类药物引起的肌病。
本研究旨在使用不同的共处理赋形剂来制备和评估含有 PITA 的不同口腔崩解片（ODT）。选择最好的 PITA-ODT 并添加 LORNO 进行重新配方，形成包含两种药物的单一 ODT。比较单一 ODT 中 PITA 和 LORNO 的药代动力学参数与市售产品（Lipidalon 和 Lornoxicam）的参数。
通过直接压缩制备了 8 种 PITA-ODT。对制备的 PITA-ODT 进行重量变化、厚度、断裂力、脆碎度、药物含量和润湿时间（WT）的评估。还评估了体外崩解时间（DT）和溶解度，并作为基于最快 DT 和最高 Q 评分标准选择最佳配方的参数。将 LORNO 添加到选定的 PITA-ODT 中，形成包含两种药物的单一 ODT（M1），并使用大鼠作为动物模型进行体内药代动力学研究，使用液相色谱-质谱联用（LC-MS/MS）分析大鼠血浆中的两种药物。
结果表明，所有 PITA-ODT 的物理性质均符合药典标准。用 Pharmaburst（F2）制备的 PITA-ODT 具有显著（<0.05）最快 DT（6.66±1.52 s）和最高 Q（79.07±2.02%），并被选为最佳配方。M1 配方的体内药代动力学研究表明，与市售产品相比，PITA 和 LORNO 的相对生物利用度（%RB）分别提高了 286.7%和 169.73%。
与市售产品相比，包含 PITA 和 LORNO 的单一 ODT 有望即时共同递送两种药物，具有更高的%RB。
