Category: Formulation and Quality
Purpose: The aim of this study was to develop solid lipid nanoparticles (SLNs) for inhalation delivery of Itraconazole for treatment of pulmonary Aspergillosis by the Hot Melt Extrusion (HME) and probe sonication techniques. Aspergillosis is an infection caused by a type of mold and can have serious effects on patients with a weak immune system or with underlying lung disease. It is effectively treated using the Itraconazole and hence to obtain a higher concentration of the drug at the site of infection, Itraconazole SLNs were prepared.
Methods: HME technique was used to prepare the SLN. The preparation involved 2 main steps; first, the formulation of a suspension by pumping the lipid and drug into the barrel and second was size reduction of the pre-suspension to obtain the nanoparticles (Figure 1). A modified screw configuration was used for the extrusion process. All the lipids used in the study were reported to be safe, biocompatible and biodegradable. The Itraconazole and the lipid (Compritol® 888 ATO/Precirol® ATO 5) was uniformly mixed and introduced into the barrel using the volumetric feeder. The surfactant (Tween® 80) was injected in the barrel using the peristaltic pump. The feeding rates of a volumetric feeder and peristaltic pump were optimized. The pre-suspension obtained was subjected to sonication for size reduction. The prepared formulation was assessed for particle size analysis, zeta potential, viscosity, entrapment efficiency, drug content, in vitro drug release, Transmission Electron Microscopy and aerodynamic properties using the cascade impactor. The in vitro release study was carried out using 10 kDa dialysis membrane bag suspended in 20 ml of release media at 37 ± 0.5 °C with 400 rpm on a magnetic stir plate.
Results: Precirol® ATO 5 was selected as a solid lipid as Itraconazole had the highest solubility in Precirol® without precipitation. Tween® 80, a surfactant, was chosen to achieve the highest drug loading, reduce the particle size and obtain a narrow PDI distribution. The particle size of the prepared formulation was observed to be 117.4 ± 1.89 nm with PDI of 0.265 ± 0.016. The zeta potential of the formulation was -19.6 ± 0.529 mV. The percent drug entrapment efficiency was found to be 99.47± 0.94%. From the release profile of Itraconazole SLNs (Figure 2) it can be observed that it exhibited a sustained release profile of Itraconazole from the developed carrier matrix with the total release of 80.21 ± 2.46% in 24 hours. In comparison to that, the release profile of the free drug solution was fast and achieved 97.16 ± 0.23 % within the first 60 mins.
Conclusion: It was observed that the Itraconazole SLNs were successfully formulated using the novel method of HME followed by probe sonication. They can provide a sustained release for 24 hours at the site of action for the treatment of pulmonary Aspergillosis.
Sushrut Marathe– Mr., University of Mississippi, University, Mississippi
Suresh Bandari– Post-doc, University of Mississippi, Oxford, Mississippi
Mahavir Chougule– University, Mississippi
Soumyajit Majumdar– Professor and Associate Dean, Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi. Oxford, MS, University, Mississippi
Michael Repka– Professor, University of Mississippi, Oxford, Mississippi