Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0581, United States.
Int J Pharm. 2012 Jul 1;430(1-2):104-13. doi: 10.1016/j.ijpharm.2012.03.050. Epub 2012 Apr 3.
This research describes the development and validation of a biorelevant in vitro release/permeation system to predict the in vivo performance of oral transmucosal dosage forms. The system is a biorelevant bidirectional transmucosal apparatus which allows better simulation of oral cavity physiological variables in comparison to compendial dissolution apparatuses and therefore may be a better predictor of in vivo behavior. The feasibility of the bidirectional apparatus was studied using smokeless tobacco (snus) as a model oral transmucosal product. In this research, nicotine release and permeation was investigated from commercially available snus using a modified USP IV flow-through apparatus, a commercially available vertical diffusion cell and a fabricated novel bidirectional transmucosal apparatus. The percent nicotine released/permeated was utilized as an input function for the prediction of in vivo plasma nicotine profiles by back calculation based on the Wagner-Nelson method. The prediction errors in C(max) and AUC(0-∞) with the USP IV flow-through device, vertical diffusion cell and novel apparatus were 4.03, 22.85 and 1.59 and -5.85, 5.85 and -9.27% respectively. This work demonstrated the suitability of the novel bidirectional transmucosal apparatus for predicting the in vivo behavior of oral transmucosal products.
本研究描述了一种用于预测口服黏膜给药剂型体内性能的生物相关体外释放/渗透系统的开发和验证。该系统是一种生物相关的双向黏膜仪器，与药典溶出仪相比，它可以更好地模拟口腔生理变量，因此可能是更好的体内行为预测器。使用无烟烟草（鼻烟）作为口服黏膜产品的模型，研究了双向仪器的可行性。在这项研究中，使用改良的 USP IV 流动通过装置、市售垂直扩散池和制造的新型双向黏膜仪器研究了商业上可获得的鼻烟中的尼古丁释放和渗透情况。释放/渗透的尼古丁百分比被用作通过基于 Wagner-Nelson 方法的反向计算来预测体内尼古丁血浆浓度曲线下面积的输入函数。USP IV 流动通过装置、垂直扩散池和新型仪器预测 C(max)和 AUC(0-∞)的误差分别为 4.03%、22.85%和 1.59%和-5.85%、5.85%和-9.27%。这项工作证明了新型双向黏膜仪器适用于预测口服黏膜给药剂型的体内行为。
