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

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.