The Influence of Solidification on the in vitro Solubilisation of Blonanserin Loaded Supersaturated Lipid-Based Oral Formulations

The Influence of Blonanserin Supersaturation in Liquid and Silica Stabilised Self-Nanoemulsifying Drug Delivery Systems on In Vitro Solubilisation

“…The composition of the SNEDDS preconcentrate used in the current study was based on a previous formulation [ 19 ], containing Miglyol 812 (36% w / w ), Capmul MCM (36% w / w ), and Cremophor EL (28% w / w ). The SNEDDS preconcentrate was formulated by rotating the lipid excipients in a glass vial for 1 h.…”

“…The S eq of BLON in the SNEDDS preconcentrate was determined in a previous study (31.4 ± 1.8 mg/mL) [ 19 ]. To determine the maximum BLON supersaturation level, the SNEDDS preconcentrate was loaded at 150%, 200%, 250%, 300%, and 350% of the S eq to fabricate liquid super-SNEDDS using the method described in Section 2.3.2 .…”

“…Next, 18 mL of FaSSIF media was continuously stirred at 37 °C in a thermostated glass container. A quantity of formulation equivalent to 3 times the S eq of BLON in undigested FaSSIF (S eq = 53 ± 2 mg/mL) [ 19 ] was placed into the container. After dispersion for 1 min, 2 mL pancreatin extract was added to initiate lipolysis.…”

“…This diminishing effect of super-SLH was attributed to a larger content of crystalline drug and less lipid available for solubilisation, highlighting that high drug loads do not necessarily correlate with improved performance, and a fine balance between drug load and performance exists. Further studies have investigated the application of super-SLH to abiraterone acetate, fenofibrate, simvastatin, and blonanserin (BLON), and have investigated the influence of different types of silica, silica geometry/microporosity, different LFCS LBF types, and liquid- vs. solid-state LBF [ 15 , 16 , 17 , 18 , 19 , 20 ].…”

“…One gap in the literature surrounding super-SLH is the influence of supersaturation level on weak bases such as BLON, and perhaps more significantly, the interaction between BLON and silica that impedes its solubilisation. Previously, Møller et al investigated the influence of lipid formulation classification type (i.e., type I vs. type II vs. type IIIA/self-nanoemulsifying drug delivery systems (SNEDDS)) and physical state (liquid LBF vs. solidified with silica) on the in vitro solubilisation of BLON from a supersaturated LBF [ 19 ]. It was reported that type IIIA formulations and liquid-state supersaturated formulations gave superior in vitro solubilisation, while solidification of the supersaturated LBF with silica significantly impeded drug solubilisation.…”