AN IN VITRO ASSESSMENT OF THE INHALED FRACTION AND PARTICLE SIZE DISTRIBUTION OF A NEBULIZED ORPHAN DRUG

• Published in: Journal of aerosol medicine and pulmonary drug delivery Vol. 24; no. 6; p. 316
• Main Authors: Cordts, E, Wagenseil, L, Buske, S, Kuhli, M, Steckel, H, Pietschmann, H, Fischer, B
• Format: Journal Article
• Language: English
• Published: 01.12.2011
• Subjects: USA; Europe; France, Paris
• ISSN: 1941-2711

AP301 is a synthetic and non-proinflammatory peptide version of a structural motif of the human Tumour Necrosis Factor alpha. It is being developed by Apeptico as a promising substance for the treatment of diverse lung diseases and has already received Orphan Drug Designation both in Europe and USA. Its clinical applications include diseases accompanied by hyper-permeable capillaries. As it is necessary to apply this orphan drug to the lungs, the intended clinical route of administration is delivery as an aerosol. Aerosolization is accomplished by nebulizing the aqueous solution with an active membrane nebulizer. As a prior study has already shown, AP301 as an aqueous solution in combination with this active nebulizer retains its pharmacological effect on ion channels in the alveolar epi-thelia tested in a patch clamp assay. Further, it is essential to gather information about the nebulizing efficiency of this novel combination of device and protein solution. Therefore, the output rate and particle size distribution of the produced aerosol were investigated using a modified Pari Compas breath simulator, a Next Generation Pharmaceutical Impactor (NGI) and laser diffraction. Quantification was carried out via UV spectroscopy. In addition, it was tested whether a variation of the drug solution concentration from 1 mg/mL to 25 mg/mL changed the nebulization behaviour and with it the particle size distribution and output rate, respectively. The study showed that an efficient nebulization of AP301 peptide solutions in a concentration range of 1 mg/mL to 25 mg/mL is possible. High fine particle fractions were obtained together with good inhalation efficiency.