Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66047, USA.
Biopharmaceutical Innovation and Optimization Center, University of Kansas, Lawrence, KS, 66047, USA.
AAPS J. 2023 Mar 22;25(3):29. doi: 10.1208/s12248-023-00799-1.
We recently developed an in vitro testing system, namely, ESCAR (Emulator of SubCutaneous Absorption and Release). The objective of this work was to investigate drug release behaviors of unmilled and milled suspensions in ESCAR. A mass transport-based model was developed to describe the multi-step drug release process, including drug dissolution, particle settling, drug distribution/partition, and drug permeation through the membrane(s). To address the particle settling effect, a correction factor was included in the model and its value was obtained by data fitting. It was found that, for both suspensions, (i) the experimental data of various dose/formulation combinations could be fit by the developed model; (ii) the dose effect on drug release was offset by the particle settling effect. This model may help to reduce experimental efforts and facilitate subcutaneous suspension formulation development using ESCAR.
我们最近开发了一种体外测试系统，即 ESCAR（皮下吸收和释放模拟器）。本工作的目的是研究未研磨和研磨混悬剂在 ESCAR 中的药物释放行为。建立了一个基于质量传递的模型来描述多步药物释放过程，包括药物溶解、颗粒沉降、药物分布/分配以及药物通过膜的渗透。为了解决颗粒沉降效应，在模型中包含了一个修正因子，其值通过数据拟合得到。结果发现，对于两种混悬剂，（i）通过开发的模型可以拟合各种剂量/配方组合的实验数据；（ii）药物释放的剂量效应被颗粒沉降效应抵消。该模型可能有助于减少实验工作量，并通过 ESCAR 促进皮下混悬剂制剂的开发。
