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Open Access
CC BY 4.0 · Pharmaceutical Fronts 2025; 07(04): e312-e324
DOI: 10.1055/a-2710-1599
Original Article

Design, Synthesis, and Optimization of New Inhalation Carriers: DBBB Series Compounds

Authors

  • Na Liu

    1   National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
    2   Shanghai Pronzen Biotechnology Co., Ltd., Shanghai, People's Republic of China

  • Huimin Chen

    2   Shanghai Pronzen Biotechnology Co., Ltd., Shanghai, People's Republic of China

  • Meng Sun

    2   Shanghai Pronzen Biotechnology Co., Ltd., Shanghai, People's Republic of China

  • Hao Wang

    2   Shanghai Pronzen Biotechnology Co., Ltd., Shanghai, People's Republic of China

  • Jianqi Li

    1   National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

  • Yu Liu

    3   Incubation Center for Science and Technology Achievements, China State Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
    4   National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
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Graphical Abstract

Abstract

In the development of dry powder inhaler (DPI) formulations, the choice and optimization of carriers are critical, as they directly impact not only drug stability and bioavailability but also patient adherence. This study sought to create and synthesize a novel DPI excipient with enhanced qualities relative to the current excipient, i.e., fumaryl diketopiperazine (FDKP). In this work, FDKP's framework was utilized to synthesize a variety of novel compounds (DBBB1–15), preserving the diketopiperazine ring and symmetrical branched chains while implementing structural alterations. The artificial intelligence software Schrödinger was employed to screen these chemicals for potential possibilities. As a result, DBBB6 was selected because of its advantageous look and physicochemical properties, including a greater pKa (reduced acidity) when compared with FDKP. The synthesis method for DBBB6 was refined, resulting in a 9.7% yield. Significantly, investigations involving rats demonstrated that DBBB6 did not induce coughing, a possible adverse effect associated with FDKP. The results indicate that DBBB6 is a viable alternative to FDKP as a DPI excipient. Its improved tolerability profile suggests a potential for reduced adverse effects. Additional studies are required to comprehensively assess its safety and efficacy for clinical application.

Keywords

DBBB series compounds - fumaryl diketopiperazine - dry powder inhaler

Supporting information

The chemical structure and 3D simulating structures ([Supplementary Table S1], available in the online version), and 1H NMR, 13C NMR, and IR spectra of FDKP and DBBB1-DBBB15 ([Supplementary Figs. S1–S46], available in the online version), can be found in the [Supporting Information] section of this article's webpage.


Ethical Approval

All animal procedures were conducted according to the Chinese legislation and regulations of Laboratory Animals of the Chinese Animal Welfare Committee. The protocols were approved by the Ethics Committee of the Center for Pharmacological Evaluation and Research (Shanghai 200437, China).


Supplementary Material



Publication History

Received: 12 March 2025

Accepted: 25 September 2025

Article published online:
06 November 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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