Novel approach for real-time monitoring of carrier-based DPIs delivery process pulmonary route based on modular modified Sympatec HELOS.
10.1016/j.apsb.2020.02.013
- Author:
Xuejuan ZHANG
1
;
Yingtong CUI
1
;
Ruifeng LIANG
1
;
Guanlin WANG
1
;
Xiao YUE
1
;
Ziyu ZHAO
1
;
Zhengwei HUANG
1
;
Ying HUANG
1
;
Jianfang GENG
2
;
Xin PAN
1
;
Chuanbin WU
1
Author Information
1. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
2. Sympatec GmbH Suzhou Rep. Office, Suzhou 215123, China.
- Publication Type:Journal Article
- Keywords:
ACI, Anderson Cascade Impactor;
APIs, active pharmaceutical ingredients;
Air flow rate;
CFD-DEM, computational fluid dynamics-discrete element method;
CIA, cascade impactor analysis;
Carrier;
Copt, optical concentration;
DPIs, dry powder inhalations;
Dry powder inhalation;
ED, emitted dose;
EDXS, energy-dispersive X-ray spectroscopy;
FC, centrifugal force;
FD, drag force;
FF, friction force;
FG, gravity;
FI, interaction force;
FPD, fine particle dose;
FPF, fine particle fraction;
HPLC, high performance liquid chromatography;
HPMC, hydroxy propyl methyl cellulose;
LAC, lactose carrier;
MFV, minimum fluidization velocity;
MMAD, mass median aerodynamic diameter;
MMSH, modular modified Sympatec HELOs;
MOC, micro orifice collector;
MSS, micronized salbutamol sulfate;
Mechanism of drug delivery;
Modular modification;
NGI, Next Generation Impactor;
O, oxygen;
PDP, pulmonary delivery process;
Pulmonary delivery process;
R, release amount;
RAUC, total release amount;
Real-time monitoring;
Rmax, maximum of release amount;
S, stopping distance;
SEM, scanning electron microscope;
Tmax, the time to Rmax;
Tt, terminal time;
U0, air flow rate;
V0, velocity;
a, acceleration;
dQ3, the volume percentage of particles within certain range;
dae, aerodynamic diameter
- From:
Acta Pharmaceutica Sinica B
2020;10(7):1331-1346
- CountryChina
- Language:English
-
Abstract:
An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values ( = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.
