Aerodynamic properties, solubility and in vitro antibacterial efficacy of dry powders prepared by spray drying: Clarithromycin versus its hydrochloride salt.
Antibiotic therapy for a direct administration to the lung in cystic fibrosis patients has to provide suitable availability, possibly in the lower respiratory tract, characterized by the presence of thick secretions. One of the crucial steps in the therapeutic management of the respiratory disease could be the drug solubilization directly in this site of action. The aim of the study was to prepare respirable powders of clarithromycin, while improving drug aqueous solubility. With this aim, several batches of micronized particles were prepared by spray drying different feed solutions, varying the solvent composition (water/isopropyl alcohol ratio), the drug concentration and pH of the liquid feeds. Particle size distribution of raw materials and engineered particles was determined using a light-scattering laser granulometer while particle morphology was assessed by scanning electron microscopy. The in vitro deposition of the micronized clarithromycin powders was evaluated by means of a Single-Stage Glass Impinger using the RS01 model7 by Plastiape® as device for the aerosolization. Solubility measurements of raw and spray-dried (SD) drug were carried out at 37°C in phosphate buffer (0.05M, pH 6.8). Results indicate that morphology and aerodynamic properties of SD particles were strongly influenced by organic solvent concentration and pH of the liquid feeds processed, both modifying drug solubility. Spherical particles and crystals were obtained at higher pH and lower organic solvent content, while wrinkled particles with very interesting aerodynamic properties and higher drug solubility were obtained at lower pH values. Thanks to a fine tuning of the process parameters and liquid feed composition, we produced SD powders with good aerodynamic properties, without using any excipients. Furthermore, SD powders of clarithromycin hydrochloric salt showed higher activity against Pseudomonas aeruginosa growth, compared to clarithromycin raw material.
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, SA, Italy.
Michele Dario
MD
Manniello
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, SA, Italy.
Pasquale
P
Del Gaudio
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, SA, Italy.
Amalia
A
Porta
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, SA, Italy.
Rita Patrizia
RP
Aquino
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, SA, Italy. Electronic address: paorusso@unisa.it.
Paola
P
Russo
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D017291:Clarithromycin / Q000737:chemistry / Q000494:pharmacology*; D004304:Dosage Forms; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D011208:Powders; D012995:Solubility
D000900:Anti-Bacterial Agents; D004304:Dosage Forms; D011208:Powders; D017291:Clarithromycin
Antibacterial activity; Clarithromycin; Cystic fibrosis; Drug solubility; Dry powder inhalers