CHARACTERIZATION OF AMPHOTERICIN-B AEROSOLS FOR INHALATION TREATMENT OF PULMONARY ASPERGILLOSIS

In recent years, the incidence of invasive pulmonary aspergillosis has increased in patients receiving immunosuppressive therapy and/or orga n transplantation. For prophylaxis against Aspergillus infections, amp hotericin B may be a useful drug when inhaled as aerosol, In this stud y, the aerosolization of amphotericin B was investigated using eight d ifferent medical nebulizers under various operating conditions and wit h different amphotericin B concentrations in the solution, The output of each nebulizer was characterized by the mass flow of spray (drug) l eaving the mouthpiece and by the size distribution of the droplets, An effective prevention of pulmonary aspergillosis via amphotericin B in halation requires a high pulmonary deposition of the drug within an ac ceptable time of administration associated with a low deposition in th e oropharyngeal region, To evaluate the dosages of drug delivered by v arious types of nebulizers to different regions of the respiratory tra ct, a semi-empirical deposition model was applied which is based on ex perimental aerosol deposition data from over 20 normal adults, The mai n results of the study are: Solutions,vith amphotericin B concentratio ns up to 10 mg/ml can be converted into sprays by means of medical neb ulizers without any problems, For most nebulizers, the slight foaming of the amphotericin B solution has no effect on the I production of th e aerosol, To optimize amphotericin B treatment of the lungs via inhal ation, sprays with mass flows above 100 mg/min and with mass median ae rodynamic diameters (MMAD) below 3 mu m should be slowly inhaled by th e subject, Applying these criteria to the nebulizers investigated, thr ee out of eight devices have proved suitable for amphotericin B treatm ent via inhalation.