Effects of lower alcohols on nanocomposite particles for inhalation prepared using O/W emulsion

Article type: Research Article

Authors: Takeuchi, Issei^{a; b; c;} | Kimura, Yukie^a | Nakajima, Takehisa^b | Makino, Kimiko^{a; b;}

Affiliations: [a] Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda, Chiba, Japan | [b] Center for Drug Delivery Research, Tokyo University of Science, Yamazaki, Noda, Chiba, Japan | [c] Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, Japan

Correspondence: [*] Corresponding authors: Issei Takeuchi, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba, 283-8555, Japan. Tel.: +81 475558855; E-mail: [email protected]. Kimiko Makino, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda, Chiba 278-8510, Japan and Center for Drug Delivery Research, Tokyo University of Science, Yamazaki, Noda, Chiba 278-8510, Japan. E-mail: [email protected]

Abstract: BACKGROUND:Inhalable nanocomposite particles using O/W emulsions were studied. The effect of the composition of the dispersed phase on the nanoparticles in the nanocomposite particles was reported, however, the effect on the inhalation characteristics of nanocomposite particles has not been investigated. OBJECTIVE:The aim of this study was to study the effects of lower alcohols in the dispersed phase of O/W emulsions on inhalable nanocomposite particles. METHODS:Nanocomposite particles were prepared using a spray dryer from O/W emulsion. A mixed solution of dichloromethane and lower alcohols in which rifampicin (RFP) and poly(L-lactide-co-glycolide) were dissolved was used as a dispersed phase, and an aqueous solution in which arginine and leucine were dissolved was used as a continuous phase. RESULTS:We succeeded in preparing non-spherical nanocomposite particles with an average diameter of 9.01–10.91 μm. The results of the fine particle fraction (FPF) measurement showed that the higher the hydrophobicity of the lower alcohol mixed in the dispersed phase, the higher the FPF value. The FPF value of the nanocomposite particles was significantly increased by using ethanol and 1-propanol. CONCLUSIONS:The results were revealed that mixing 1-propanol with the dispersed phase increased the amount of RFP delivered to the lungs.

Keywords: Nanocomposite particles, poly(L-lactide-co-glycolide), inhalation, lower alcohols, fine particle fraction

DOI: 10.3233/BME-211244

Journal: Bio-Medical Materials and Engineering, vol. 33, no. 3, pp. 159-168, 2022