Effect of finasteride particle size reduction on its pharmacokinetic, tissue distribution and cellular permeation

Drug Delivery

Tarek A. Ahmed¹  Ahmed M. Al-Abd² 

[1]Department of Pharmaceutics, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia

[2]Department of Pharmaceutics and Industrial Pharmacy, Al-Azhar University, Cairo, Egypt

[3]Department of Pharmacology, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia

[4]Department of Pharmacology, Medical Division, National Research Centre, Giza, Egyp

关键词: Finasteride;    micro and nanoparticles;    pharmacokinetics;    tissue distribution;    BPH;   

DOI  :  10.1080/10717544.2018.1440446

来源: publisher

【 摘 要 】

Finasteride (FSD), a specific competitive inhibitor of the steroid type-II 5α-reductase enzyme, is used in treatment of benign prostate hyperplasia (BPH) and male pattern baldness. The drug is of limited solubility that affect its dissolution and bioavailability. The aim was to study the effect of FSD particle size reduction on the pharmacokinetic, tissue distribution and cellular permeation. An optimized drug micro- and nano-particles were developed, characterized, administered to group of rats, and systemic pharmacokinetic and tissue distribution within target and not-target organs were determined using near-infrared (NIR) spectroscopy technique. Moreover, the cellular permeation of the prepared formulations through normal prostate epithelial cells was assessed and compared to pure FSD. The developed micro- and nano-particles were of 930 and 645 nm, respectively. Plasma maximum drug levels (Cmax) and overall exposure (AUC) of both formulations were not significantly higher than unformulated drug. However, micronized FSD achieved significant higher concentration within the target tissue (prostate) within the current study compared to pure drug and nano-sized formulation as well. Yet, this is explained by the higher sequestration ability of spleen tissue to the nano-sized formula compared to micro-sized FSD. At the cellular level, permeation of nano-sized FSD through prostate epithelial cells was superior to the unformulated FSD as well as the micro-sized drug formulation. FSD particle size reduction significantly influences its cellular permeation and to a lesser extend affect its systemic pharmacokinetics and tissue distribution after oral administration.

【 授权许可】

CC BY