Preparation and Evaluation of Dry Powder Inhaler (DPI) Formulation for Fixed Dose Combination of Bronchodilators

Abstract

Dry powder inhaler (DPI) represents a significant advanced pulmonary delivery technology for lung targeting. DPI is considered to be environmental friendly formulation as they eliminates the use of hydro fluorocarbon propellants compared to pressurized metered dose inhaler (MDI). DPI consists of micronized drug blended with larger carrier particles; which increases flow properties by reduction in aggregation. Upon actuation of DPI during inhalation; the formulation is fluidized releasing micronized drug particles from carrier particles and travels towards deeper regions of Lungs. Fixed dose combination (FDC) of anti-muscarinic agent and β-2 agonist have been developed by innovator with the aim to treat chronic bronchitis and emphysema. In the present invention, the attempts were made to develop formulation bypassing patent by eliminating magnesium stearate from formulation. Developed FDC formulations were evaluated for various parameter like bulk density, tapped density, flow property, angle of repose, particle size distribution, assay, blend uniformity, uniformity of delivered dose and deposition of emitted dose. Initially, various types of carrier agents were explored alone as well as in combination at different proportions; and compared with that of innovator formulation. Based on preliminary study lactose was found to be most suitable carrier. Various grades of fine and coarse lactose were explored in different proportion. The formulation parameters were finalized based on optimum ratio of fine and coarse grade of lactose. Further variation were made in the process parameters like mixing process and mixing time to optimize the formulation. The physical and chemical stability of drug & excipients were studied by drug-excipient compatibility studies for one month, and results were found within specified limit. In conclusion, the developed formulation was found to be equivalent with that of Innovator product without patent bypass.