Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia; Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Int J Pharm. 2022 Jul 25;623:121958. doi: 10.1016/j.ijpharm.2022.121958. Epub 2022 Jun 26.
Drug overdose connected to marketed pharmaceutical products, particularly opioids, occurs at an alarming rate. Novel strategies through innovative formulation approaches that reduce the likelihood of overdose while allowing safe therapeutic outcomes are urgently required. The current study provides a proof-of-concept for a new formulation approach by co-formulating drug with a lipase inhibitor within a solid lipid formulation in order to prevent or reduce the harmful effects of taking multiple doses of an oral solid dose form. Lipase inhibitor controlled-release (LICR) formulations were created using a simple hot melt method to co-formulate the inhibitor (orlistat) and ibuprofen, as the model drug, within the lipid matrix. The digestion and drug release kinetics were determined using an in vitro lipolysis model. Above a threshold level of orlistat there was decreased digestibility of multiple doses of the LICR formulations, leading to reduced drug release. Upon administration of the formulations in capsules to rats, the LICR formulation displayed the lowest exposure of ibuprofen during the pharmacokinetic studies. This novel formulation approach shows promise in preventing accidental drug overdose after oral administration of multiple doses of formulation.
药物过量与市售药物产品（特别是阿片类药物）有关，其发生率令人震惊。目前迫切需要通过创新的配方方法来制定新的策略，这些方法既能降低药物过量的可能性，又能确保安全的治疗效果。本研究通过将药物与脂肪酶抑制剂共同配制在固体脂质制剂中，为新的配方方法提供了一个概念验证，以防止或减少多次服用口服固体制剂的有害影响。使用简单的热熔法制备了脂肪酶抑制剂控释（LICR）制剂，将抑制剂（奥利司他）和布洛芬（作为模型药物）共同配制在脂质基质中。使用体外脂肪分解模型测定了消化和药物释放动力学。在奥利司他达到阈值水平以上时，多个 LICR 制剂的消化能力降低，导致药物释放减少。在将这些制剂以胶囊形式施用于大鼠后，在药代动力学研究中，LICR 制剂显示出最低的布洛芬暴露量。这种新的配方方法有望防止口服多次服用制剂后意外发生药物过量。
