Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

• Published in: Pharmaceutical research Vol. 35; no. 2; pp. 28 - 15
• Main Authors: Mangal, Sharad, Nie, Haichen, Xu, Rongkun, Guo, Rui, Cavallaro, Alex, Zemlyanov, Dmitry, Zhou, Qi (Tony)
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2018; Springer; Springer Nature B.V
• Subjects: Administration, Inhalation; Amino acids; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Azithromycin; Azithromycin - administration & dosage; Azithromycin - pharmacokinetics; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chemical properties; Dissolution; Drug Carriers - chemistry; Drug Compounding - methods; Drug Liberation; Dry Powder Inhalers; Drying; Formulation and Manufacturing of Solid Dosage Forms; Health aspects; Humans; Infection; Inhalation; Inhalers; Leucine; Leucine - chemistry; Medical Law; Morphology; Particle Size; Pharmacology/Toxicology; Pharmacy; Physicochemical properties; Powder; Research Paper; Respiratory tract diseases; Respiratory Tract Infections - drug therapy; Solubility; aerosol performance; dissolution; L-leucine; poorly water soluble drug; solubility; azithromycin; dry powder inhaler; spray drying
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-017-2334-9

Purpose Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. Methods The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. Results The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. Conclusions We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.