Development and characterization of a carrier-free dry powder inhaler formulation of clarithromycin

Abstract

Carrier-free systems are a highly substantial research area due to the side effects of excipients on the lungs and the limited number of excipients suitable for lung-targeted drug delivery systems. The goal of this study is the preparation of a carrier-free dry powder inhaler (DPI) formulation containing clarithromycin for the treatment of pneumonia. Solutions of clarithromycin in methanol:water mixtures were turned into respirable microparticles by the spray-drying process. Ammonium carbonate was added to the formulations at concentrations between 0.05 % and 3.00 % (w/v), and the effect of the ammonium carbonate concentration on the formulations was investigated in terms of surface characteristics, particle size, and zeta potential. Following these studies, thermal behavior (thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis), chemical interactions (fourier transform infrared (FT-IR) analysis), crystallinity (X-ray diffraction (XRD) analysis), antimicrobial activity, aerodynamic performance with Next Generation Impactor (NGI), surface area, and moisture content were evaluated. It was determined that the formulation F9, containing 0.50 % (w/v) ammonium carbonate, had the most convenient features for lung targeting. It exhibited a nearly spherical shape. Its d50 = 4.76 +/- 0.05 & micro;m, zeta potential =-21.4 +/- 1.5 mV, mass median aerodynamic diameter (MMAD) = 5.08 & micro;m, fine particle fraction (FPF) = 19.65 %, surface area = 1.773 m2/g, and moisture content = 3.023 %. TGA, DSC, and XRD confirmed the formation of different polymorphs. Two considerable outcomes were obtained after this study. First, an effective DPI formulation was obtained without the need for carriers, using the applied production method. Second, a drug candidate was developed that is more efficient than the conventional antibiotic clarithromycin (minimum inhibitory concentrations (MICs) of the optimum formulation and untreated clarithromycin are 0.15 and 0.30 & micro;g/mL, and minimum bactericidal concentrations (MBCs) of the optimum formulation and untreated clarithromycin are 1.22 and 4.88 & micro;g/mL, respectively) by providing local treatment for pneumonia.