TY - JOUR
T1 - Investigation of the molecular state of 4-aminosalicylic acid in matrix formulations for dry powder inhalers using solid-state fluorescence spectroscopy of 4-dimethylaminobenzonitrile
AU - Tse, Jun Yee
AU - Kadota, Kazunori
AU - Yang, Zhijun
AU - Uchiyama, Hiromasa
AU - Tozuka, Yuichi
N1 - Funding Information:
This research was supported by the Hosokawa Powder Technology Foundation (Osaka, Japan), and Osaka University of Pharmaceutical Sciences International Exchange Grant . The authors thank Shin-Etsu Chemical Co., Ltd. for providing Grade E HPMC and Hitachi Automotive Systems Measurement, Ltd., for providing the Jethaler.
Publisher copyright:
© 2019 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.
PY - 2019/10
Y1 - 2019/10
N2 - Carrier-free method is an alternative approach for dry powder inhaler (DPI) formulations, which overcome poor drug mobility and distribution. Here we investigated the properties of an active pharmaceutical ingredient (API) within composite particles. We used highly-branched cyclic dextrin (HBCD) as the excipient matrix that was prepared using a spray-drying technique. 4-Aminosalicylic acid (4-ASA) and 4-dimethylaminobenzonitrile (DMABN) were selected as a hydrophilic second-line antitubercular agent and a surrogate for 4-ASA as a model compound, respectively. The spray-dried particles (SDPs) containing 4-ASA or DMABN with HBCD had geometric median diameters (D50) of 2.34 ± 0.07 μm and 2.26 ± 0.10 μm, respectively. Further, the in vitro aerodynamic properties were similar for SDPs containing 4-ASA and DMABN with HBCD. To determine the properties of APIs within composite particles, we performed solid-state fluorescence spectroscopy of DMABN. As a candidate excipient, hydroxypropyl methylcellulose (HPMC) was compared to HBCD. We determined the intensity ratio of twisted intramolecular charge transfer (TICT) emission to locally excited emission within the excipient matrix environment. The HBCD matrix environment was better than HPMC to trigger a more robust TICT reaction of DMABN. A potent state-changing interaction of APIs occurred in the HBCD matrix environment versus another excipient environment.
AB - Carrier-free method is an alternative approach for dry powder inhaler (DPI) formulations, which overcome poor drug mobility and distribution. Here we investigated the properties of an active pharmaceutical ingredient (API) within composite particles. We used highly-branched cyclic dextrin (HBCD) as the excipient matrix that was prepared using a spray-drying technique. 4-Aminosalicylic acid (4-ASA) and 4-dimethylaminobenzonitrile (DMABN) were selected as a hydrophilic second-line antitubercular agent and a surrogate for 4-ASA as a model compound, respectively. The spray-dried particles (SDPs) containing 4-ASA or DMABN with HBCD had geometric median diameters (D50) of 2.34 ± 0.07 μm and 2.26 ± 0.10 μm, respectively. Further, the in vitro aerodynamic properties were similar for SDPs containing 4-ASA and DMABN with HBCD. To determine the properties of APIs within composite particles, we performed solid-state fluorescence spectroscopy of DMABN. As a candidate excipient, hydroxypropyl methylcellulose (HPMC) was compared to HBCD. We determined the intensity ratio of twisted intramolecular charge transfer (TICT) emission to locally excited emission within the excipient matrix environment. The HBCD matrix environment was better than HPMC to trigger a more robust TICT reaction of DMABN. A potent state-changing interaction of APIs occurred in the HBCD matrix environment versus another excipient environment.
KW - Dry powder inhaler
KW - Fine particle fraction
KW - Solid-state fluorescence spectroscopy
KW - Twisted intramolecular charge transfer
UR - http://www.scopus.com/inward/record.url?scp=85070297469&partnerID=8YFLogxK
U2 - 10.1016/j.apt.2019.07.027
DO - 10.1016/j.apt.2019.07.027
M3 - Journal article
AN - SCOPUS:85070297469
SN - 0921-8831
VL - 30
SP - 2422
EP - 2429
JO - Advanced Powder Technology
JF - Advanced Powder Technology
IS - 10
ER -