Czyz, Stefan, Wewers, Martin, Finke, Jan, Kwade, Arno, Van Eerdenbrugh, Bernard, Juhnke, Michael and Bunjes, Heike (2020) Spray 1 drying of API nanosuspensions: Importance of particle size, matrix former content and drying temperature for successful formulation and process development. European journal of pharmaceutics and biopharmaceutics, 152 (July). pp. 63-71. ISSN 1873-3441; 0939-6411

Abstract

Active pharmaceutical ingredient (API) nanosuspensions from naproxen (Nap) and itraconazole (Itra) stabilized with Kollidon®VA64 (KVA) and sodium dodecylsulfate (SDS) were produced in two different size classes each by wet media milling. These API nanosuspensions were spray dried with lactose, trehalose and sucrose as matrix formers in different proportions and at different drying temperatures (Toutlet). Toutlet as well as the API content significantly influenced the redispersibility of the API nanoparticles. It could be shown that these two parameters are related to each other, with an increasing API content leading to a decreasing maximum applicable Toutlet (Tcritical). Drying above the Tcritical always led to a change in the nanoparticulate state and thus to a non-redispersible product (with respect to the defined quality criteria). For each proportion of API to matrix former a Tcritical could be found. Tcritical showed a linear relation to the API content. The linear regression of this relation was defined as process boundary. The y-intercept of the process boundary correlated well with the Tg of the pure matrix former used for spray drying. The two API under investigation led to virtually identical behaviour if other parameters were kept constant. The particle size of the initial nanosuspension seems to have an important influence. Nanosuspensions with comparatively small particle sizes led to significantly lower process boundaries compared to the use of larger particle sizes. The maximum API content that leads to a redispersible product is thus determined decisively by the particle size of API nanoparticles, Toulet and the Tg of the matrix former used.

Item Type:	Article
Date Deposited:	23 May 2020 00:45
Last Modified:	23 May 2020 00:45
URI:	https://oak.novartis.com/id/eprint/40542