Abstract for presentation at Chemeca 2005

Purpose. The purpose was to investigate the effect of fine lactose (FL) and different sizes of lactose carrier on the dissolution of 20% indomethacin in interactive mixtures. Methods. Interactive mixtures containing micronised indomethacin (Sigma, USA) were prepared using povidone-lactose granules (Lac-PVP), lactose spray-dried and lactose monohydrate (106-250 μm). Two other size fractions of Lac-PVP were used (53-106 & 250-355 μm). Ternary mixtures contained added FL (5% & 10% w/w). The particle size distributions were measured using a Malvern Mastersizer S (Malvern Instruments, Malvern, UK). The dissolution of the indomethacin mixtures was measured using an automated DT-6 Erweka dissolution apparatus (Erweka, Germany) following the USP paddle method. Dissolution data were modelled using Sigma Plot software. SEM (Hitachi S-570- Japan) was used to examine the different particles at several magnifications. Results. Dissolution data followed a bi-exponential model representing dissolution from dispersed and agglomerated particles (R2 > 0.99). The estimated initial concentration of agglomerates (Ca) of the indomethacin-Lac-PVP mixture was significantly smaller than that of the other mixtures (P < 0.001), while there was no significant difference among the dissolution rate constants (P > 0.096). The Lac-PVP contained a high concentration of FL (4.7% < 5 μm) which was adhered strongly to the granule surface, while FL associated with the lactose monohydrate carrier was mainly detached from its surface. Adding FL to the indomethacin-Lac-PVP mixture did not result in any significance difference in Ca, while there was a significant decrease in Ca when FL was added to the other lactose mixtures (P < 0.024). Decreased lactose carriers size caused a decreased Ca for the three fractions of Lac-PVP. Conclusions. FL in the carrier was likely to produce indomethacin-FL agglomerates with lower tensile strength leading to decreased agglomeration and improved dissolution rates.