Evaluating the role of lactose anomeric composition in tablet disintegration and dissolution: a hidden variable in pharmaceutical formulation

Abstract

Lactose, a chiral excipient, is widely used in the pharmaceutical industry as a diluent because it is safe and has developable physical properties. However, there are stability issues; β lactose powder stored at 40 °C/75% RH will epimerize from the β to the α chiral form within 7 days. The influence of lactose chiral composition on medicine stability is poorly understood but is likely to be valuable when ensuring the safety and effectiveness of the finished pharmaceutical product (FPP). Therefore, the aim of this study was to investigate the effect of the anomeric composition of lactose on tablet properties. Tablets with a higher α lactose content (79.5/20.5 α/β % w/w (α79%)) demonstrated faster disintegration times when compared to tablets formulated with a higher β content (13.5/86.5 α/β % w/w (α13%)), i.e., 27 s compared to 220 s. Differences in tablet hardness (p ≤ 0.05) were also observed, with tablets containing a higher α composition exhibiting higher hardness (i.e., 207 N as opposed to 170 N under a 40 kN compression force). The release of acetylsalicylic acid was found to be faster from tablets that were formulated with ‘aged’ or epimerised lactose (α79%) compared to those produced using β lactose, as received (α13%), the respective T₉₀ values being 60 and 91 min. To conclude, it is apparent that the stereoisomeric effects of lactose excipients on tablets are evident, and therefore, the measurement of anomeric content is advised prior to tablet manufacture.