Pharmaceutica Analytica Acta

Abstract

Development and Evaluation of Aerodynamic Particle Size Distribution of Inhalable Spray Dried Rifampicin Loaded Steric Acid-Chitosan Nanomicellar Micro-Composites Dry Powder Inhaler by Qbd Approach with Dual Analysis by TSI/ACI Deposition Study

Ashwin J Mali*, Nirav J Javiya and Atmaram P Pawar

The present work deals with the development of spray-dried Rifampicin-Loaded Nanomicellar Micro Composites (RFP-NMC) by Quality by Design (QbD) approach. The RFP-NMC was prepared by oil in water emulsion solvent evaporation technique and optimized by the 3 full factorial designs. The stearic acid (X₁) and chitosan (X₂) were selected as Critical Quality Attributes (CQA’s) while particle size (Y₁) and % drug content (Y₂) as dependent factors. The data was represented by QbD Minitab software. The in vitro lung deposition of RFP-NMC was evaluated by Twin Stage Impinger (TSI) and by Andersen Cascade Impactor (ACI). Further, in vitro release was carried out by dialysis method in Simulated Lung Fluid (SLF) and cytotoxicity was assessed by MTT assay. The optimized formulation depicted a particle size of 5.85 µm ± 0.38 µm and drug content of 77.20% ± 1.04%. The infrared spectra, X-ray diffraction spectra and scanning electron microscopy revealed no significant structural alternations with the amorphous and spherical nature of the microcomposites. The in vitro dialysis study reflected 90% of drug release in 24 hours. The optimized formulation exhibited Fine Particle Fraction (FPF) and Mean Median Aerodynamic Diameter (MMAD) of 52.66% ± 1.23% and 2.96 µm ± 0.04 µm with optimum flow properties. The in vitro cytotoxicity study on A 549 cell line established a lack of toxicity of formulation. The present investigation has proved the excellent aerodynamic properties and deposition efficiency of RFP-NMC which further can be explored for enhanced lung delivery.

Published Date: 2023-08-18; Received Date: 2023-07-18