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Della Bella A, Müller M, Danani A, et al. Effect of Lactose Pseudopolymorphic Transition on the Aerosolization Performance of Drug/Carrier Mixtures. Pharmaceutics. 2019;11(11)doi: 10.3390/pharmaceutics11110576.
Della Bella, A., Müller, M., Danani, A., Soldati, L., & Bettini, R. (2019). Effect of Lactose Pseudopolymorphic Transition on the Aerosolization Performance of Drug/Carrier Mixtures. Pharmaceutics, 11(11), . https://doi.org/10.3390/pharmaceutics11110576
Della Bella, Andrea, et al. "Effect of Lactose Pseudopolymorphic Transition on the Aerosolization Performance of Drug/Carrier Mixtures." Pharmaceutics vol. 11,11 (2019). doi: https://doi.org/10.3390/pharmaceutics11110576
Della Bella A, Müller M, Danani A, Soldati L, Bettini R. Effect of Lactose Pseudopolymorphic Transition on the Aerosolization Performance of Drug/Carrier Mixtures. Pharmaceutics. 2019 Nov 04;11(11). doi: 10.3390/pharmaceutics11110576. PMID: 31689975; PMCID: PMC6920796.
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Pharmaceutics. 2019 Nov 04;11(11). doi: 10.3390/pharmaceutics11110576.

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

Pharmaceutics

Andrea Della Bella, Michele Müller, Andrea Danani, Luciano Soldati, Ruggero Bettini

Affiliations

  1. Food and Drug Department, University of Parma, 43124 Parma, Italy. [email protected].
  2. Micro-Sphere S.A., Ponte Cremenaga, 6996 Monteggio, Switzerland. [email protected].
  3. Istituto Delle Molle di Studi Sull'Intelligenza Artificiale, Scuola Universitaria Professionale Della Svizzera Italiana, 6928 Manno, Switzerland. [email protected].
  4. Micro-Sphere S.A., Ponte Cremenaga, 6996 Monteggio, Switzerland. [email protected].
  5. Food and Drug Department, University of Parma, 43124 Parma, Italy. [email protected].

PMID: 31689975 PMCID: PMC6920796 DOI: 10.3390/pharmaceutics11110576

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.

Keywords: DPI; aerosolization performance; lactose; polymorphism

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