Drug delivery to the lung in Cystic Fibrosis: deposition, dissolution, mucus interaction and microbiological evaluation of dry powder inhalers

Abstract

The inhalation therapy consists of a direct administration of drugs for the treatment of lung diseases. A formulation for inhalation is a valid option in the symptomatic management of pulmonary diseases typical of cystic fibrosis (CF). This is a rare hereditary disease that affects the normal function of the exocrine glands of the mucosa, with the production of a dry and poorly flowing mucus even in the respiratory tract. The first objective of my PhD project was to evaluate the rheological behaviour of the CF sputum samples, kindly donated by the “G. Gaslini” Hospital of Genoa. Following the in vitro addition of HCO3 - to the sputum samples, a decrease in the viscosity of this material was therefore evaluated, compared to samples pre-treated with water alone. To verify if this evidence was accompanied by an increase in permeation of a drug through this sample, the second purpose was to evaluate the permeation of a drug through CF sputum. The Ketoprofen lysinate, a formulation in dry powder, called Dry Powder Inhaler (DPI), already developed in previous research work was selected. As the results show, the viscosity decrease was therefore accompanied by an increase in the permeation of the drug only after the addition of HCO3 - to the sputum samples... [edited by Author]