Alternative matrix formers for nanosuspension solidification: Dissolution performance and X-ray microanalysis as an evaluation tool for powder dispersion

Abstract

Four alternative matrix formers [Avicel ®PH101, Fujicalin ® (CaHPO 4), Aerosil ®200 (SiO 2) and Inutec ®SP1] were evaluated for their capability in preserving rapid dissolution after spray-drying of nanosuspensions. Model drug compounds selected were cinnarizine (CIN), itraconazole (ITR) and phenylbutazone (PHB) as they showed a decrease in dissolution rate upon spray-drying in the absence of additional matrix formers, yielding release values after 5 min of dissolution (release 5 min ) of 57.7 ± 1.0% (CIN), 56.3 ± 3.8% (ITR) and 67.4 ± 1.3% (PHB). Compared to the situation without matrix former inclusion, the performance of Avicel ®PH101 was good for CIN (release 5 min = 90.9 ± 7.7%), intermediate for PHB (release 5 min = 81.0 ± 6.4%) and poor for ITR (release 5 min = 42.1 ± 4.2%). For Fujicalin ®, intermediate (PHB: release 5 min = 87.7 ± 3.0%) or poor (CIN: release 5 min = 66.1 ± 3.4%; ITR: release 5 min = 55.9 ± 5.2%) performance was seen. Results for Aerosil ®200 were good for all compounds (CIN: release 5 min = 91.5 ± 2.5%; ITR: release 5 min = 83.8 ± 3.4%; PHB: release 5 min = 95.5 ± 2.4%), indicating that the large specific surface area was in this case translated into good matrix forming capabilities. Finally, the best results were obtained for Inutec ®SP1 (CIN: release 5 min = 88.7 ± 1.2%; ITR: release 5 min = 93.4 ± 2.4%; PHB: release 5 min = 101.3 ± 4.9%). Except for Avicel ®PH101, Cl-maps from X-ray microanalysis of the itraconazole powders supported the hypothesis that better dispersion of drug in the powders results in faster dissolution.