Effect of Lactose Pseudopolymorphic Transition on the Aerosolization Performance of Drug/Carrier Mixtures

Abstract

Physico-chemical properties of lactose are key factors in adhesive mixtures used as dry powder inhaler (DPI). Despite the abundant literature on this topic, the effect of the polymorphism and pseudo-polymorphism of lactose has been seldom investigated and discussed although often lactose used in DPI is subjected to unit operations, which may alter its solid-state properties. Here, we studied the aerosolization performance of salbutamol sulphate (SS) or budesonide (BUD) formulations by investigating the effect of lactose pseudopolymorphism in ternary (coarse lactose/fine lactose/drug) and binary (coarse lactose/drug) mixtures. An improvement of the aerosolization performance of SS formulations with the increase of the amount of fine micronized lactose up to 30% (fine particle fraction (FPF) = 57%) was observed. Micronized lactose contained hygroscopic anhydrous α-lactose, which converted to α-lactose monohydrate at ambient conditions. This implied that the positive effect of fines on the aerosolization performance decreased and eventually disappeared with the formulation aging. Positive effect on SS deposition was observed also with binary mixtures with anhydrous lactose, whereas the opposite occurred with budesonide-containing formulations. The collected data demonstrated the crucial role of the carrier crystal form on the positive effect of fines on the deposition.

Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance

“…Della Bella et al [ 18 ] demonstrated the strong relationship between lactose crystal phase and aerosolization performance both with hydrophilic and lipophilic model drugs. The role of solid-state properties, such as those induced by grinding/micronization [ 19 ], on respirability performance has been evidenced by several other authors [ 5 , 8 , 20 , 21 ].…”

Stability and In Vitro Aerodynamic Studies of Inhalation Powders Containing Ciprofloxacin Hydrochloride Applying Different DPI Capsule Types

“…There is also a stricter 90–110% requirement in the industry [ 38 ]. The novel combined carrier-based formulation (2) is also in line with the latter as SD < 5% was obtained (94.17 ± 3.34%), so homogeneity can be assumed [ 49 ]. Before the start of the stability period, the DPI capsules were filled with powders in the knowledge of specific drug content.…”

Development of an Innovative, Carrier-Based Dry Powder Inhalation Formulation Containing Spray-Dried Meloxicam Potassium to Improve the In Vitro and In Silico Aerodynamic Properties

“…The industrial standard is generally more stringent, often set between 90 and 110% [54]. Our carrier-based formulations also meet the latter more stringent criteria in the blending uniformity test; thus, homogeneity can be assumed (SD < 5%) [70]. Based on the calculated drug content, the exact amount of the compositions was determined to be filled into the capsules for performing the in vitro study.…”