The Effect of Crystalline and Amorphous Lactose on Mechanical Properties of Roller Compaction Ribbons and Tablets

Abstract

Lactose is a widely used excipient in the pharmaceutical industry. It exists as anhydrous, alpha- and beta- monohydrate forms, which can be either crystalline or amorphous. Commercially available lactose comes in various grades differentiated by physical forms as well as modifications such as particle size. These characteristic modifications enable formulation and processing. Lactose grades for direct compression applications for example, contain various concentrations of crystalline and amorphous content. The mixture of forms exhibit unique material compaction properties that facilitate performance within formulations. Lactose is infrequently used in large concentrations for dry granulation processes because alpha-lactose monohydrate exhibits relatively poor binding properties and consolidates mainly by fragmentation due to its `brittleness'. Though this is true of crystalline lactose, previous direct compaction research has found that amorphous lactose is known to be more compressible than its crystalline form. This research aims to characterize the material properties of a directly compressible lactose monohydrate, Flowlac 100 containing high crystalline and high amorphous content; and to compare the fundamental differences in mechanical properties when manufactured by dry granulation via a roller compaction emulator. Ribbon properties such as tensile strength and solid fraction were measured, and the subsequent mechanical properties of tablets evaluated. Additionally, model drug formulations containing a very brittle drug, paracetamol, were manufactured into ribbons with high crystalline and high amorphous lactose. Subsequent tablettability was also evaluated. Results from this research suggest that amorphous lactose offers advantages over its crystalline counterpart such as an increased ribbon tensile strength under lower compression forces. A formulation containing amorphous lactose and a poorly compressible model drug manufactured through a roller compaction process resulted in acceptable tablets with improved friability over the crystalline formulation.