Faculty of Pharmacy, Department of Pharmaceutical Technology, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan.
Faculty of Pharmacy, Jerash University, Jerash, 26150, Jordan.
AAPS PharmSciTech. 2022 Sep 22;23(7):262. doi: 10.1208/s12249-022-02420-8.
Chitosan is a natural, biocompatible polymer. The aim of this work was to study the influence of drug solubility in 2% v/v acetic acid, formulation parameters, on mean hydrodynamic (MHD) diameters and drug entrapment efficiencies (% EE) into chitosan-TPP nanoparticles (NPs). Drugs of different aqueous solubilities with nearly similar molecular weights were chosen and admixed at several concentrations in 2% acetic acid at different chitosan concentrations and at fixed chitosan to TPP concentrations/volumes ratios. The NPs were freeze-dried, and the supernatants were utilized to determine % EE. Theophylline- and antipyrine-loaded NPs showed the best short-term physical stability in terms of MHD diameters. Antipyrine-loaded NPs possessed the larger MHD diameters, while vitamin C-loaded NPs showed the smallest ones. The relationships between the ratio of drug concentration relative to their solubilities in acetic acid were almost linear for antipyrine and vitamin C-loaded NPs when plotted against and the MHD diameters of NPs, and linear for antipyrine- and theophylline-loaded NPs when plotted against % EE with antipyrine NPs possessing the highest % EE. However, vitamin C- and propylthiouracil-loaded NPs exhibited curvilinear patterns with comparatively lower % EE. The concentration of chitosan, drug solubility in dispersion medium, and the ratio of the concentration of admixed drug relative to its solubility in dispersion medium were found critical in determining % EE and MHD diameters of NPs. It was evident that drugs with extremely low or high solubilities in dispersion medium resulted in low % EE when admixed at both low and high concentrations.
壳聚糖是一种天然的、生物相容的聚合物。本工作旨在研究药物在 2%（v/v）醋酸中的溶解度、制剂参数对壳聚糖-TPP 纳米粒子（NPs）的平均水动力（MHD）直径和药物包封效率（% EE）的影响。选择了几种不同水溶性但分子量相近的药物，并在不同壳聚糖浓度下，在 2%醋酸中以不同浓度混合，同时固定壳聚糖与 TPP 的浓度/体积比。将 NPs 冷冻干燥，并利用上清液测定% EE。茶碱和安替比林载药 NPs 在 MHD 直径方面表现出最佳的短期物理稳定性。安替比林载药 NPs 的 MHD 直径最大，而维生素 C 载药 NPs 的 MHD 直径最小。当将药物浓度与它们在醋酸中的溶解度的比值与 NPs 的 MHD 直径进行线性拟合时，安替比林和维生素 C 载药 NPs 的比值几乎呈线性关系，而当将药物浓度与它们在醋酸中的溶解度的比值与% EE 进行线性拟合时，安替比林和茶碱载药 NPs 也呈线性关系，其中安替比林载药 NPs 的% EE 最高。然而，维生素 C 和丙硫氧嘧啶载药 NPs 表现出曲线模式，具有相对较低的% EE。壳聚糖浓度、药物在分散介质中的溶解度以及混合药物浓度与分散介质中溶解度的比值被发现是决定 NPs 的% EE 和 MHD 直径的关键因素。很明显，当药物在低浓度和高浓度下混合时，在分散介质中溶解度极低或极高的药物的% EE 都很低。
