http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Henriques Patrícia,Bicker Joana,Carona Andreia,Miranda Margarida,Vitorino Carla,Doktorovová Slavomíra,Fortuna Ana 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.5
Purpose Amorphous solid dispersions (ASD) for nasal delivery offer the opportunity to increase drug release performance, while using polymers with mucoadhesive properties. The aim of the present study was to apply this solubility enhancement technique to a poorly soluble drug for nasal delivery, while comparing two particle engineering strategies, namely spray dried microparticles and chimeral agglomerates, with the corresponding physical blends with crystalline drug. Methods Formulations of piroxicam were manufactured using varied polymer and particle engineering strategies and evaluated through in vitro drug release and ex vivo permeation studies, as well as nasal deposition and in vivo pharmacokinetic studies. Results ASD with hydroxypropyl methylcellulose (HPMC) showed enhanced drug release and permeation, compared to polyvinylpyrrolidone/vinyl acetate formulations and blends. Nasal deposition of HPMC chimeral agglomerates suggested off-target deposition. In vivo pharmacokinetic studies revealed that spray-dried HPMC-containing microparticles exhibited the highest maximum plasma concentration (Cmax) and the lowest time to attain it (tmax). In vitro release rate and in vivo absorption rate were correlated as well as tmax and in vitro performance. When excluding the formulation with least nasal targeted deposition, in vitro release and ex vivo permeation performance were also correlated with Cmax and area under the drug concentration-time curve (AUC) from 0 to 1 h, with R2 > 0.89. Conclusion ASD for nasal delivery provide fast drug absorption, which depends on the supersaturation ability of the polymer employed. In vitro-in vivo correlations suggested that in vitro release and ex vivo permeation studies are predictive tools regarding nasal absorption.