(W0930-05-31) Repurposing Amodiaquine as a Dry Powder Inhaled Formulation for Respiratory Disorders

Purpose: Despite progress in early screening and alternative therapies, non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths. Unfortunately, the limited treatment options and the acquired drug resistance to current therapies necessitate the urgent development of new treatment strategies. Our earlier studies showed the potential of an antimalarial, Amodiaquine (AQ), to be developed as anti-NSCLC therapy. However, AQ suffers from rare life-threatening side effects that necessitate local lung delivery. In this project, we aim to develop an inhalable dry powder of amodiaquine for direct delivery to the lungs. We have investigated the feasibility of widely used spray drying technology in developing inhaled powder formulation of AQ for NSCLC treatment.

Methods: Spray drying of amodiaquine was performed using mannitol and L-leucine as carriers in different ratios using one nozzle Buchi Mini Spray Dryer B-290. 30% of the amodiaquine drug load was taken for all batches. A 2% w/v aqueous solution was spray dried at a feed rate of 20%, aspirator 100%, and inlet temperature 100^oC. The powder was collected, and the % yield was calculated for all the formulations. All developed formulations were characterized for drug content, DSC, SEM, PXRD, and in-vitro aerosolization through Next-Generation Impactor. The stability studies of spray-dried AQ-loaded powder formulations are ongoing by keeping the powders at 4^oC and room temperature for 2 months. The stability samples will be analyzed for drug content, powder drug amorphicity, and aerosolization properties.

Results: The highest % yield of spray-dried powder was obtained with Formulation F4, containing 25% mannitol and 75% l-leucine (81.6± 1.2%), with significant drug loading (334.6±28.5 µg/mg) (Fig. 1). Therefore, F4 was chosen for further characterization tests. The DSC and PXRD data revealed that the formulation was semicrystalline in nature (Fig. 2). SEM images of the formulation showed that the particles were round and smooth on the surface (Fig. 3). According to in-vitrodrug aerosolization studies, the MMAD of this formulation was 1.3±0.1 mm. On the other hand, the % FPF value was found to be 86.24±1.27%, which is appropriate for deep lung deposition. The MMAD and FPF values suggest that the powder is suitable for inhalation.

Conclusion: Current results showed the successful development of an inhalable dry powder of amodiaquine with spray dry technology for non-small cell lung cancer. In-vitro and preclinical efficacy studies of inhaled AQ-loaded spray-dried powder are currently underway.

Acknowledgements: The authors acknowledge Ms. Druvsarika Barji, St. John’s University, for her help in learning the spray drying technology.

Figure 1: Formulations with % yield

Figure 2:- (A) DSC thermograms of formulations, (B)PXRD analysis of formulations

Figure 3: (A) % Deposition, (B) Scanning Electron Microscopy of formulation (F4)