DEVELOPMENT OF CAPSULE BASED DRY POWDER FOR INHALATION CONTAINING GLYCOPYRRONIUM BROMIDE

*Geeta K. Patel and Kaushal V. Patel

ABSTRACT

A capsule based unit dose dry powder for inhalation of long acting muscarinic antagonist, Glycopyrronium bromide with the device Turbospin® #3 dry powder inhaler was prepared to obtain increased drug deposition in the alveolar absorptive region with a view to treat bronchospasm associated with chronic obstructive pulmonary diseases. The influence of different inhalation grade -lactose monohydrate as carrier on the drug-to-carrier interaction and the performance of lactose-based dry powder inhaler formulations were evaluated. The Glycopyrronium bromide (< 5 m) was incorporated with lactose of different grades and their combinations as carriers to deliver dose using an inhaler device. Solid-state characteristics of the carrier as well as the drug powder were assessed by particle size and distribution measurement. The aerosol behavior of the powder was studied by dispersion using Turbospin® connected to a twin-stage liquid impinger (TSLI) operating at flow rates of 60 Lit/min. Significant differences in aerosol performance of Glycopyrronium bromide measured as fine particle fraction (FPF) from the carriers was observed with different grade inhalation lactose. Specifically, as carrier size increased, FPF decreased. Different weight ratios and different size ranges for the fines with coarse lactose showed significant change for in vitro deposition of the drug from formulation. Primary packaging material like hard gelatin capsule and HPMC capsule influenced the DPI performance during the storage period. Formulation containing 70:30 mixture of respitose SV003 and sorbolac 400 as carrier imparts well disaggregation of drug and higher fine particle fraction was achieved at 60 Lit/min. Thus the object of the present invention is to provide DPI comprise LAMAs, allows highly efficient and sufficient amount of dosing when inhaled by the patients even in a low pressure.

Keywords: Long acting muscarinic antagonist, dry powder inhaler, fine particle fraction, twin-stage liquid impinger, drug-to-carrier interaction.