Development of a Dry Powder Inhaler and Nebulised Nanoparticle-Based Formulations of Curcuminoids for the Potential Treatment of Lung Cancer. Development of Drug Delivery Formulations of Curcuminoids to the Lungs using Air Jet Milling and Sonocrystallisation Techniques for Dry Powder Inhaler Preparations; and Nanoemulsion and Microsuspension for Nebuliser Formulations

Abstract

Curcuminoids have strong anticancer activities but have low bioavailability. The highest rate of cancer deaths comes from lung tumours; therefore, inhaled curcuminoids could treat lung cancer locally. To date, there are no nebulised formulations of curcuminoids, and there are no inhalable curcuminoids particles without excipients using air jet mill and sonocrystallisation methods for DPI formulations. It is the first time; the aerodynamic parameters of curcumin, demethoxycurcumin and bisdemethoxycurcumin were measured individually using NGI. The size, shape, free surface energy, and the crystal polymorphism of the produced inhalable curcuminoid particles were characterised using laser diffraction, SEM, IGC, DSC and XRPD, respectively. Several DPI formulations with a variable particle size of curcuminoids were prepared in two drug-carrier ratios (1:9 and 1:67.5). The best performance of the DPI formulations of the sonocrystallised particles, which exist in crystal structure form1, were obtained from ethanol- heptane, as illustrated FPF 43.4%, 43.6% and 43.4% with MMAD of 3.6µm, 3.5µm and 3.4µm, whereas the best DPI formulation of the air jet milled particles was presented FPF 38.0%, 38.9%, and 39.5% with MMAD of 3.6µm, 3.4µm and 3.2µm for curcumin, demethoxycurcumin and bisdemethoxycurcumin, respectively. Nebulised curcuminoids using nanoemulsion and microsuspension formulations were prepared. The physical properties, such as osmolality, pH and the viscosity of the aerosolised nanoemulsion and the microsuspension formulations were determined. The FPF% and MMAD of nebulised nanoemulsion ranged from 44% to 50% and from 4.5µm to 5.5µm respectively. In contrast, the FPF% of microsuspension ranged from 26% to 40% and the MMAD from 5.8µm to 7.05µm. A HPLC method was developed and validated in order to be used in the determination of curcuminoids from an aqueous solution.