Zaid Abdel Naser, Zohud Nihal, E'layan Bushra, Aburadi Tasneem, Jaradat Nidal, Ali Iyad, Hussein Fatima, Ghanem Mashhour, Qaddomi Aiman, Abu Zaaror Yara
Department of Pharmacy.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus.
Drug Des Devel Ther. 2017 Nov 21;11:3291-3298. doi: 10.2147/DDDT.S138926. eCollection 2017.
Orlistat is an irreversible inhibitor of the lipase enzyme that prevents trigylcerides from being digested, thereby inhibiting triglyceride hydrolysis and absorption. The resultant reduced calorie uptake enables a positive effect on weight control. Systemic absorption of the drug is, therefore, not necessary for its mode of action. An alternative in vitro study (pharmacodynamic) has been introduced for this drug, as in vivo bioavailability studies are irrelevant with regard to the achievement of the product's intended purposes.
To develop a new validated high-performance liquid chromatography (HPLC) method for the analysis of orlistat and to assess the potency and equivalence of three orlistat formulations using the pharmacodynamic method as a surrogate indicator of pharmaceutical interchangeability.
A new HPLC method was developed for the analysis and for the dissolution studies of orlistat in capsules. Pancreatic lipase activity was measured for three different capsule products: Orlislim, Slimcare, and Xenical, G1, G2, and the brand, respectively. Porcine pancreatic lipase and p-nitrophenyl butyrate (PNPB) were placed in a pH 7.4 reaction buffer at 37°C, and substrate hydrolysis was monitored by measuring absorbance changes at 410 nm; this was repeated on six capsules of each product. The inhibition was expressed by the concentration of product, which inhibited 50% of the activity of pancreatic lipase (IC).
The new analytical method was suitable for orlistat analysis. Values of IC from regression lines and equations were 6.14, 8.43, and 7.80 μg/mL for Orlislim, Xenical, and Slimcare, respectively.
Pharmacodynamic studies of lipase inhibition could be used to support in vitro dissolution, which demonstrates interchangeability between generic and branded orlistat capsules. Moreover, it could be suggested as an alternative tool to bioequivalence studies for orlistat oral products.
奥利司他是一种脂肪酶的不可逆抑制剂，可阻止甘油三酯被消化，从而抑制甘油三酯的水解和吸收。由此减少的热量摄取对体重控制产生积极作用。因此，该药物的全身吸收对其作用方式并非必要。由于体内生物利用度研究与该产品预期目的的实现无关，因此已针对此药物引入了一项替代体外研究（药效学）。
开发一种经过验证的新型高效液相色谱（HPLC）方法用于分析奥利司他，并使用药效学方法作为药物可互换性的替代指标来评估三种奥利司他制剂的效力和等效性。
开发了一种新型HPLC方法用于分析奥利司他及其胶囊的溶出度研究。分别对三种不同的胶囊产品（Orlislim、Slimcare和赛尼可，分别为G1、G2和品牌产品）测量胰脂肪酶活性。将猪胰脂肪酶和对硝基苯丁酸酯（PNPB）置于37°C的pH 7.4反应缓冲液中，并通过测量410 nm处的吸光度变化监测底物水解；对每种产品的六个胶囊重复此操作。抑制作用以抑制50%胰脂肪酶活性（IC）的产品浓度表示。
新的分析方法适用于奥利司他分析。Orlislim、赛尼可和Slimcare的回归线和方程得出的IC值分别为6.14、8.43和7.80 μg/mL。
脂肪酶抑制的药效学研究可用于支持体外溶出度研究，这证明了仿制药和品牌奥利司他胶囊之间的可互换性。此外，它可被建议作为奥利司他口服产品生物等效性研究的替代工具。
