Gattefossé, Paramus, NJ, USA.
Gattefossé Group, Saint-Priest, France.
AAPS PharmSciTech. 2022 May 20;23(5):151. doi: 10.1208/s12249-022-02282-0.
The importance of lipid-based formulations in addressing solubility and ultimately the bioavailability issues of the emerging drug entities is undeniable. Yet, there is scarcity of literature on lipid excipient chemistry and performance, notably in relation to oxidative stability. While not all lipid excipients are prone to oxidation, those with sensitive moieties offer drug delivery solutions that outweigh the manageable oxidative challenges they may present. For example, caprylocaproyl polyoxylglycerides help solubilize and deliver cancer drug to patients, lauroyl polyoxylglycerides enhance the delivery of cholesterol lowering drug, and sesame/soybean oils are critical part of parenteral nutrition. Ironically, excipients with far greater oxidative propensity are omnipresent in pharmaceutical products, a testament to the manageability of oxidative challenges in drug development. Successful formulation development requires awareness of what, where, and how formulation stability may be impacted, and accordingly taking appropriate steps to circumvent or meet the challenges ahead. Aiming to fill the information gap from a drug delivery scientist perspective, this review discusses oxidation pathways, prooxidants, antioxidants, and their complex interplay, which can paradoxically take opposite directions depending on the drug delivery system.
不可否认，基于脂质的制剂对于解决新兴药物实体的溶解度和最终生物利用度问题非常重要。然而，关于脂质赋形剂化学和性能的文献很少，特别是关于氧化稳定性方面的文献。虽然并非所有脂质赋形剂都容易氧化，但那些具有敏感部分的赋形剂提供了药物输送解决方案，其优势超过了它们可能带来的可管理的氧化挑战。例如，辛酸/癸酸甘油酯有助于溶解并向患者输送抗癌药物，月桂酰聚氧甘油酯增强了降胆固醇药物的递送，芝麻油/大豆油是肠外营养的重要组成部分。具有更大氧化倾向的赋形剂在药物产品中无处不在，这证明了在药物开发中可以应对氧化挑战。成功的制剂开发需要了解制剂稳定性可能受到哪些方面、哪些位置以及如何受到影响，并相应地采取适当的措施来规避或应对未来的挑战。本综述从药物输送科学家的角度出发，旨在填补这一信息空白，讨论了氧化途径、促氧化剂、抗氧化剂及其复杂的相互作用，这些作用可能根据药物输送系统而走向相反的方向。
