Tailoring lactose particles with various porosities for N-Acetylcysteine delivery to the lungs using porogens and templating agents

Abstract

Creating porous lactose with a low density and a large surface area is an attractive carrier, especially for inhalation therapy, as it can load drugs in pores as well as on its surface, thereby enhancing its aerosolization performance. Porogens and templating agents are common pore-forming techniques that can be employed to create porous materials. N-acetylcysteine (NAC) is an effective mucolytic with anti-inflammatory and antioxidant properties for cystic fibrosis and idiopathic pulmonary fibrosis treatment, which was selected as a drug in the current study. Due to its gastrointestinal side effects and patient compliance, its oral administration is not ideal. Therefore, the current study developed DPI formulations containing porous lactose generated through pore-forming techniques. To this end, the present study compares the effects of ammonium bicarbonate as a porogen and citric acid/boric acid as templating agents on spray-dried porous lactose properties, including density, angle of repose, and yield percentage. Specific surface area study showed the highest surface area of 19 m²/g for lactose sample produced via the addition of 10 % ammonium bicarbonate and the smallest surface area (1.4 m²/g) was obtained for lactose sample with the addition of 1 % boric acid/2 % citric acid to spray the spray-dried solution. These samples showed about 59 % and 54 % crystallinity, respectively. Aerosolization properties of lactose powder with the highest surface area containing NAC showed a mass median aerodynamic diameter of 3.5 μm with a geometric standard deviation of 3.9, whereas these values for the least surface area powder were 2.4 μm and 4.2. The results showed fine particle fractions of 11 and 18 %, for DPI formulations containing the highest and lowest surface lactose powder, respectively. Results indicated that both pore-forming agents were capable of producing lactose particles with various porosities to obtain different aerosolization performances.