Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, 21201, USA.
Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
J Pharm Sci. 2023 Mar;112(3):751-759. doi: 10.1016/j.xphs.2022.09.030. Epub 2022 Oct 4.
A dissolution-hollow fiber membrane (D-HFM) system with relatively high area/volume ratio was previously characterized and showed favorably high percent drug absorption. Also, it's in vitro permeation constant (K) was close to in vivo human permeation constant (k). The objective of the current study was to predict the in vivo human absorption profile and biopharmaceutic performance of five drug products using the D-HFM system. Four immediate-release (IR) and one extended-release (ER) solid oral dosage form were subjected to the D-HFM system. Tablets and capsule dissolution were also measured using USP apparatus II. Drug solutions were also subjected to D-HFM testing. Predicted and observed absorption profiles in D-HFM system showed close agreement for each solid oral dosage form. Levy-Polli plots from D-HFM system successfully predicted the four IR products to be low biopharmaceutic risk due to permeation rate limited or mixed dissolution/permeation rate limited absorption, and successfully predicted metoprolol ER product to be high biopharmaceutic risk due to dissolution rate limited absorption. These observations showed potential of the in vitro D-HFM system to be utilized in biopharmaceutics risk assessment of in vivo tablet and capsule performance.
先前已经对具有相对较高的面积/体积比的溶解-中空纤维膜（D-HFM）系统进行了表征，结果表明其药物吸收百分比较高。此外，其体外渗透常数（K）接近体内人体渗透常数（k）。本研究的目的是使用 D-HFM 系统预测五种药物产品的体内人体吸收曲线和生物药剂学性能。四种速释（IR）和一种缓释（ER）固体制剂均经过 D-HFM 系统测试。还使用 USP 仪器 II 测量了片剂和胶囊的溶出度。D-HFM 系统预测的吸收曲线和观察到的吸收曲线非常吻合。D-HFM 系统的 Levy-Polli 图成功预测了四种 IR 产品的生物药剂学风险较低，因为渗透速率受限或混合溶解/渗透速率受限吸收，并且成功预测了美托洛尔 ER 产品的生物药剂学风险较高，因为溶解速率受限吸收。这些观察结果表明，体外 D-HFM 系统有可能用于评估体内片剂和胶囊性能的生物药剂学风险。
