Optimizing The Formulation and Evaluation of Inhaled Corticosteroidal Suspension For The Treatment of Asthma and Copd

Abstract

The study aims to optimise and evaluate the budesonide inhalation micro-suspension and develop a formulation by reducing the particle size, which will ultimately enhance the stability and performance. Budesonide binds and activates the glucocorticoid receptor in the cytoplasm of effector cells (e.g., bronchi), which then translocate the Budesonide glucocorticoid complex in the bronchi, where it binds to HDAC2 and CBP (HAT). The formulation is a dispersion system in which, polysorbate 80 was used as a surface active agent along with the buffering agent, chelating agent, stability enhancer, osmolality adjuster, and pH regulators as per reference product, reverse engineering and IIG. OFAT was used to optimise the process. The combination of homogenizers like HSH and HPH aided in achieving the target particle size and ultimately optimising the formulation. Stability and wetting were achieved by manipulating the concentration of the surfactant in two phases of the formulation. Physio-chemical, in-vitro and in-vivo analysis was conducted for the optimised batch. The evaluation parameters were performed like; product- description, density, pH, osmolality, viscosity, shelf life, RS, assay, APSD, DSD, FPD, FPF, GSD, MMAD, DSC, XRD, Electron microscopy, FE-SEM, FTIR, Water loss (for container study), in-vivo study- body weight analysis, organ/ lung weight analysis, histopathology studies (of tracheal tissue, tracheal lining and lung tissue), blood cell count (e.g., WBC count, lymphocyte count, monocyte count, granulocyte count, and MPV), blood serum analysis (e.g., concentration of TNF α, LDH, and ALP), and BALF analysis (e.g., leucocyte count, eosinophil count, and AEC). The results indicated a stable, safe and more efficacious micro-suspension as compared to the marketed formulation