Compaction behavior and optimization of spray-dried lactose with various amorphous content

Abstract

The purpose of this study was to investigate the influence of amorphous content in spray-dried lactose on tableting characteristics. To obtain different amorphous contents, spray-dried lactoses were prepared at various lactose concentrations in distilled water. Plain spray-dried lactose and hydrochlorothiazide-lactose based tablets were compressed on an instrumented tablet press. Heckel analysis indicated that relative density (D B ) and yield pressure (P y ) correlated with both the degree of crystallinity and particle size and shape. The compatibility of the tablets was found to increase with amorphous content up to 20 % and then decreased and leveled off as the amorphous content was greater than 30 %. At 30 % amorphous and higher the spray-dried lactose tablets exhibited dissolution and erosion rather than disintegration in distilled water which was observed with lower amorphous lactose. The results indicated that tablet disintegration was influenced by compaction pressure and amorphous level (p < 0.05). Amorphous level was a major variable on tablet disintegration whereas compaction pressure affected tablet strength (p < 0.05). The optimal amorphous content and compaction force were evaluated by multiple response optimization using response surface methodology to achieve desirable tablet properties, i.e., maximum crushing strength, minimum disintegration time, minimum time at 50 % drug release and minimum friability. The best condition was observed at amorphous content 10-20 % and compaction force 150-250 MPa.