TY - JOUR

T1 - Role of dispersion enhancer selection in the development of novel tratinterol hydrochloride dry powder inhalation formulations

AU - Liu, Tingting

AU - Tong, Shiqing

AU - Liao, Qianqian

AU - Pan, Li

AU - Cheng, Maosheng

AU - Rantanen, Jukka

AU - Cun, Dongmei

AU - Yang, Mingshi

N1 - Funding Information: This work was financially supported by the National Major Scientific and Technological Special Project for “Significant New Drug Development” of China (No. 2018ZX09739009), the Liaoning Pan Deng Xue Zhe Scholar (No. XLYC2002061), and the Overseas Expertise Introduction Project for Discipline Innovation (“111 Project”) (No. D20029). T.L. would like to thank the China Scholarship Council (No. 201908210308) and NordForsk for the Nordic University Hub project #85352 (Nordic POP, Patient Oriented Products) for financial support. D.C. acknowledges financial support from the Guiding Project for Science and Technology of Liaoning Province (No. 2019-ZD-0448), and Ministry of Education Chunhui Program (LN2019017). Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - Tratinterol hydrochloride (TH) is a new long-acting bronchodilator with strong β2 adrenoceptor stimulation activity. The aim of this study was to design a new carrier-based dry powder inhalation (DPI) formulation for TH and to investigate the effect of dispersion enhancers on the aerosol performance of TH in vitro. To this end, coarse lactose was used as a carrier. TH was micronized by using a jet mill and blended with the carrier to obtain a reference DPI formulation. Commercial magnesium stearate (MgSt) as received, micronized MgSt (MgSt-M), and fine lactose (FL) were used as the dispersion enhancers and formulated with the micronized TH (TH-M) and the carrier as DPI formulations. The obtained DPI formulations were characterized using dynamic light scattering (DLS), X-ray powder diffraction (XRPD), thermal analysis, powder rheometer, and Raman microscopy. A next generation pharmaceutical impactor (NGI) was used to evaluate the aerodynamic performance of the dry powders. The results showed that TH-M was in an inhalable particle size range, and based on the XRPD and thermal analysis, the solid form of TH-M did not change compared to the starting materials. The NGI results showed that the fine particle fraction (FPF) of TH could be increased with the addition of MgSt and FL as dispersion enhancers in the reference formulation. In addition, the FPF of TH could be increased with a decrease in the particle size of MgSt or an increase in the amount of FL. A combination of MgSt-M and FL could further improve the aerosol performance of TH. Raman spectroscopic imaging confirmed the spatial location of MgSt and TH at the surface of the carrier. This study demonstrates that TH could be formulated into carrier-based dry powder formulation for inhalation using coarse lactose as the carrier. The dual strategy based on using both MgSt and FL as dispersion enhancers improved the aerosol performance of a novel TH dry powder formulation.

AB - Tratinterol hydrochloride (TH) is a new long-acting bronchodilator with strong β2 adrenoceptor stimulation activity. The aim of this study was to design a new carrier-based dry powder inhalation (DPI) formulation for TH and to investigate the effect of dispersion enhancers on the aerosol performance of TH in vitro. To this end, coarse lactose was used as a carrier. TH was micronized by using a jet mill and blended with the carrier to obtain a reference DPI formulation. Commercial magnesium stearate (MgSt) as received, micronized MgSt (MgSt-M), and fine lactose (FL) were used as the dispersion enhancers and formulated with the micronized TH (TH-M) and the carrier as DPI formulations. The obtained DPI formulations were characterized using dynamic light scattering (DLS), X-ray powder diffraction (XRPD), thermal analysis, powder rheometer, and Raman microscopy. A next generation pharmaceutical impactor (NGI) was used to evaluate the aerodynamic performance of the dry powders. The results showed that TH-M was in an inhalable particle size range, and based on the XRPD and thermal analysis, the solid form of TH-M did not change compared to the starting materials. The NGI results showed that the fine particle fraction (FPF) of TH could be increased with the addition of MgSt and FL as dispersion enhancers in the reference formulation. In addition, the FPF of TH could be increased with a decrease in the particle size of MgSt or an increase in the amount of FL. A combination of MgSt-M and FL could further improve the aerosol performance of TH. Raman spectroscopic imaging confirmed the spatial location of MgSt and TH at the surface of the carrier. This study demonstrates that TH could be formulated into carrier-based dry powder formulation for inhalation using coarse lactose as the carrier. The dual strategy based on using both MgSt and FL as dispersion enhancers improved the aerosol performance of a novel TH dry powder formulation.

KW - Dispersion enhancer

KW - Dry powder inhalation

KW - Fine lactose

KW - Magnesium stearate

KW - Tratinterol hydrochloride

U2 - 10.1016/j.ijpharm.2023.122702

DO - 10.1016/j.ijpharm.2023.122702

M3 - Journal article

C2 - 36773729

AN - SCOPUS:85148354384

VL - 635

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 122702

ER -