Conversion of α-lactose monohydrate to anhydrous form with superior tabletability by twin-screw extrusion at elevated temperature

• Published in: International journal of pharmaceutics 2020-10, Vol.588, p.119790-119790, Article 119790
• Main Authors: Batra, Amol, Desai, Dipen, Serajuddin, Abu T.M.
• Format: Article
• Language: English
• Subjects: Anhydrous lactose; Excipient; Lactose monohydrate; Tablet; Twin-screw extruder
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119790

[Display omitted] The purpose of this study was to improve tabletability (tensile strength versus compaction pressure) of α-lactose monohydrate by twin screw extrusion (TSE) near its dehydration temperature but below its melting point. When extruded at 150 and 160 °C, α-lactose monohydrate converted completely to α-lactose anhydrous that was mostly crystalline and only partially amorphous; the latter was indicated by glass transition observed in DSC scans. Tabletability of the material thus obtained by TSE was superior to anhydrous lactose available commercially or produced by hot air oven drying at 160 °C. The superior tabletability was attributed to the partial conversion to amorphous lactose. When samples of anhydrous lactose powders obtained by TSE or oven drying were exposed to 25 °C/60% RH and 40 °C/75% RH, they reverted to the monohydrate with decreased tabletability. However, when anhydrous lactose powders produced by TSE were first compressed into tablets with high tensile strength and then exposed to similar stability testing conditions, there was no decrease in the tensile strength of tablets. Rather, it further increased, possibly due to the interaction of the amorphous fraction of lactose with moisture. Thus, TSE not only increased tabletability of α-lactose monohydrate, the compressed tablets remained intact and hard during shelf-life. These results demonstrate that a new modified anhydrous lactose may be produced by TSE that has better tabletability and superior physical stability than α-lactose monohydrate and the commercially available anhydrous lactose.