Badal Tejedor, Maria, Pazesh, Samaneh, Nordgren, Niklas, Rutland, Mark, Schuleit, Michael, Alderborn, Göran and Millqvist Fureby, Anna (2018) Milling induced amorphisation and recrystallisation of α-lactose monohydrate. International journal of pharmaceutics, 537. pp. 140-147. ISSN 1873-3476; 0378-5173

Abstract

Preprocessing of pharmaceutical powders is a common procedure to condition the materials for a better manufacturing performance. Good flowability and tabletability properties are essential to avoid problems during tablet manufacturing. Nonetheless preprocessing operation units not always fulfill the desired goal but also may induce undesired material properties modifications. Material induced amorphization when conditioning particle size through milling is an example. Surface and bulk modifications on the material structure will change material properties affecting the procesability of the powder. So it is essential to control the material transformations that occur during milling. Topographical and mechanical changes in surface properties can be a preliminary indication of further material transformations. Therefore an initial surface evaluation of the α-lactose monohydrate after short and prolonged milling times has been performed in the present study. Unprocessed α-lactose monohydrate and spray dried lactose were evaluated in parallel to the milled samples as reference examples of the crystalline and amorphous lactose structure. Morphological differences between unprocessed α-lactose, 1h and 20h milled lactose and spray dried lactose were visually detected with SEM and AFM. Additionally, AFM was used to simultaneously characterized particles surface amorphicity by measuring energy dissipation (eV). An extended surface amorphicity was detected after 1h of milling while prolonged milling times showed a moderate surface particle amorphization. Bulk material characterization performed with DSC indicated a partial amorphicity for the 1h milled lactose and a fully amorphous thermal profile for the 20h milled lactose, however, last one shifted in temperature values from that of the amorphous reference. This suggests a surface-bulk propagation of the amorphicity during milling in combination to a different amorphous structural conformation than the amorphous spray dried lactose. This might turn into a crystalline-like surface behavior of the 20h milled lactose. Water loss during milling was measured with TGA showing lower water content for the lactose amorphized through milling. This contributes to the surface hardening of the long term milled sample detected with AFM. Thus, bulk characterization confirms the amorphization phenomena induced through milling which differs from the amorphous structure formed by spray drying. That is already reflected in the materials surface properties measured with AFM.

Item Type:	Article
Keywords:	tableting, milling,mechanical properties, AFM,DSC,TGA
Date Deposited:	19 Jan 2018 00:45
Last Modified:	19 Jan 2018 00:45
URI:	https://oak.novartis.com/id/eprint/31776