title: Quantitative determination of micronization-induced changes in the solid state of lactose.
abstract: Lactose, in particular α-lactose monohydrate, is the most used carrier for inhalation. Its surface and solid-state properties play a key role in determining Dry Powder Inhalers (DPIs) performance. Techniques such as X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC), which are commonly used for the characterization of lactose, are not always capable of explaining the solid-state changes induced by processing, such as micronization. In the present work, the evaluation of the effect of the micronization process on the solid-state properties of lactose was carried out by XRPD and DSC and a satisfactory, although not unequivocal, interpretation of the thermal behaviour of lactose was obtained. Thus, a new gravimetric method correlating in a quantitative manner the weight change in specific sections of the Dynamic Vapour Sorption (DVS) profile and the amount of different forms of α-lactose (hygroscopic anhydrous, stable anhydrous and amorphous) simultaneously present in a given sample was developed and validated. The method is very simple and provides acceptable accuracy in phase quantitation (LOD=1.6, 2.4 and 2.7%, LOQ=5.4, 8.0 and 8.9% for hygroscopic anhydrous, stable anhydrous and amorphous α-lactose, respectively). The application of this method to a sample of micronized lactose led to results in agreement with those obtained by DSC and evidenced that hygroscopic anhydrous α-lactose, rather than amorphous lactose, can be generated in the micronization process. The proposed method may find a more general application for the quantification of polymorphs of compounds different than lactose, provided that the various solid phases afford different weight variations in specific regions of the DVS profile.
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Della Bella
authors.affiliation: Micro-Sphere SA, Ponte Cremenaga, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.affiliation: Micro-Sphere SA, Ponte Cremenaga, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Soldati
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Elviri
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy. Electronic address: bettini@unipr.it.
authors.forename: R
authors.initials: R
authors.lastname: Bettini
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D007785:Lactose
keywords: Dynamic vapour sorption; Inhalation carrier; Lactose; Micronization; Polymorphism; Quantitative analysis; Thermal analysis