Development of Breath Actuated Inhaler with Optimization of combination therapy of Pressurized Metered Dose Inhaler pMDI to control Asthma and Chronic Obstructive Pulmonary Diseases COPD

Abstract

This research work concerns investigations of novel pressurized metered dose inhaler pMDI formulations containing Formoterol Fumarate FF and Beclomethasone Dehydrate Propionate BDP in association with a breath actuated Inhaler device BAI. Various formulation trials and process variables were studied using in vitro methods to determine their influence on the performance of these novel formulations. newlineThe special efforts were made to arrest the interactions of BDP with HFA Propellant, due to increased solubility of BDP in HFA 134a propellant systems leads to agglomerates formation. The said interactions of Beclometasone were controlled in by coated dissolved BDP in hydrophilic solvent, co-solvent macro molecular excipient i.e., Polyethylene Glycol 1000. Due to this developed formulation was found to significantly improve supendability of drug particles in HFA propellant system, it impacted positively on the fine particle fraction FPF fine particle dose FPD. Formoterol and Beclomethasone formulated in HFA 134ea resulted in slightly greater canister pressure as compared to HFA 227 Propellant systems. newlineWith respect to the evaluation and testing methods were constructed based on calibration curve and LOD and LOQ identification followed by the analytical method validation UV Spectrophotometer Method according to ICH guidelines Q2 R1 for final formulation and methods for Assay was found very robust, accurate and precise. newlineThe assessment of risk associated with formulation has been evaluated and controlled by applying the QbD principles by identifying the formulation various QTTP and CQA. The robust manufacturing process developed and optimized by using the Design of Experiments to study the impact or influence of various process variables on formulation CQAs such Content per Can CPC, Emitted Dose ED and Assay.