Oktay Ayşe Nur, Polli James E
University of Health Sciences Türkiye Gülhane Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Türkiye.
University of Maryland, Department of Pharmaceutical Sciences, Baltimore, USA.
Turk J Pharm Sci. 2025 Sep 5;22(4):270-278. doi: 10.4274/tjps.galenos.2025.70367.
Norvir oral powder [ritonavir (RTV)] employs polyvinylpyrrolidone/vinyl acetate as the polymer to formulate an amorphous solid dispersion. Its oral absolute bioavailability is 70% in the fasted state, and it has negative food effects. The aim of this study was to perform in vitro dissolution of Norvir powder and Wagner-Nelson deconvolution of data under fasted, moderate fat, and high fat conditions in order to elucidate the relevance of dissolution testing.
dissolution of Norvir oral powder was conducted, and the human pharmacokinetic data of Norvir powder were obtained from literature, under fasted, moderate fat, and high fat conditions. Wagner-Nelson deconvolutions were performed. The absolute fraction absorbed (F) profiles were compared to the dissolution (F) profiles. Levy-Polli plot analysis was also conducted. For each pharmacokinetic condition, a scale factor was estimated to approximate the extent to which dissolution needed to be slowed down to mimic dissolution.
Qualitatively, there was a large difference between and dissolution. dissolution showed 98% release in 5 minutes. Meanwhile, from Wagner-Nelson analysis, only 5.5% of the drug dissolved (and absorbed) in 5 min under fasted conditions. It was not until 2 hr that 49% of the RTV dose dissolved (and was absorbed) . , moderate fat and high fat conditions were even slower in producing a certain effect. The Levy-Polli plot exhibited a "reverse-L" profile. It was concluded that such rapid dissolution did not mimic the dissolution of RTV.
Biopharmaceutic consideration of dissolution, pharmacokinetics, and deconvolution analysis indicated that dissolution was "too rapid" to adequately mimic dissolution. Findings suggest greater inspection of methods for poorly water-soluble drugs, especially those drugs where absorption is expected to be rate-limited by dissolution.
诺维乐口服粉剂[利托那韦（RTV）]采用聚乙烯吡咯烷酮/醋酸乙烯酯作为聚合物来制备无定形固体分散体。其口服绝对生物利用度在禁食状态下为70%，且存在食物负效应。本研究的目的是在禁食、中等脂肪和高脂肪条件下对诺维乐粉剂进行体外溶出，并对数据进行Wagner-Nelson反卷积，以阐明溶出度测试的相关性。
在禁食、中等脂肪和高脂肪条件下进行诺维乐口服粉剂的溶出实验，并从文献中获取诺维乐粉剂的人体药代动力学数据。进行Wagner-Nelson反卷积。将绝对吸收分数（F）曲线与溶出（F）曲线进行比较。还进行了Levy-Polli图分析。对于每种药代动力学条件，估计一个比例因子，以近似模拟溶出所需减慢溶出速度的程度。
定性地说，体外溶出和体内溶出之间存在很大差异。体外溶出在5分钟内显示98%释放。同时，根据Wagner-Nelson分析，在禁食条件下，仅5.5%的药物在5分钟内溶解（并吸收）。直到2小时，才有49%的RTV剂量溶解（并被吸收）。中等脂肪和高脂肪条件下产生一定效果的速度甚至更慢。Levy-Polli图呈现出“倒L”形曲线。得出结论，这种快速的体外溶出不能模拟RTV的体内溶出。
生物药剂学对体外溶出、体内药代动力学和反卷积分析的考虑表明，体外溶出“太快”，无法充分模拟体内溶出。研究结果表明，对于难溶性药物，尤其是那些预期吸收受溶出速率限制的药物，需要对体外溶出方法进行更严格的检查。
