Quantifying the loading capacity of a carrier-based DPI formulation and its dependence on the blending process

TL;DR

This study introduces a combined analytical approach to accurately quantify the loading capacity of fines on carrier particles in dry powder inhalation formulations, highlighting the influence of mixing processes on product quality.

Contribution

It presents a novel, reproducible method combining sieve analysis, microscopy, and permeability measurements to assess loading capacity and fines behavior in carrier-based DPI formulations.

Findings

The proposed method is accurate and reproducible.

Mixing parameters significantly affect loading capacity.

Different analytical methods yield consistent results.

Abstract

Non-segregating ordered powder mixtures constituted by a coarse carrier fraction and finer components are at the basis of dry powders for inhalation pharmaceuticas. The estimation of the loading capacity, i.e. how many fines can be hosted on each carrier particle, is crucial to grant the product quality through a reproducible and affordable manufacturing process. We propose an approach based on the combination of sieve analysis, optical microscopy and powder bed permeability to quantify the loading capacity and understand the fines behavior, the impact of the mixing process was also investigated. We tested the method on model binary mixtures composed only of a coarse lactose carrier and micronized lactose fines as a surrogate of a real active pharmaceutical ingredient. The results provided by the different methods are consistent, the approach proved to be accurate and reproducible. The effect of different mixing parameters and equipment on the loading capacity is also discussed.