Olukayode Imole

EFFECT OF PROCESS VARIABLES AND MATERIAL FLOW ON FILLING CONSISTENCY AND FINAL PERFORMANCE OF LACTOSE-BASED DRY POWDER INHALER FORMULATIONS
Targeted delivery of highly potent, complex, low-dose of active pharmaceutical ingredients (API) into the pulmonary tract using dry powder inhalers (DPIs) is a common option for treating respiratory diseases like Chronic Obstructive Pulmonary Disease (COPD) and Asthma. In typical DPI formulations, one or more micronized (1-5 microns) active pharmaceutical ingredients (APIs) are blended together with a coarse excipient such as lactose, which acts as a carrier. Ternary formulations including mixing of different excipients are also becoming increasingly popular. To obtain a final drug formulation that produces the desired efficacy, it is known that equipment selection, equipment operating variables, material flow characteristics and filling consistency (into blisters or capsules) are of critical importance. However, not much research has been done to investigate the interplay between these factors.
The aim of the present investigation is to understand the correlation of machine operating variables and blend flow properties to the filling consistency and final performance of different lactose-magnesium stearate-based dry powder inhaler formulations. The Cyclomix® – a vertical high shear, high impact mixer – is used to perform the blends. It is expected, among others, that the results would help formulators in making critical decisions during the early phases of drug development and also for post-approval changes.