The Influence of Solidification on the in vitro Solubilisation of Blonanserin Loaded Supersaturated Lipid-Based Oral Formulations
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The Influence of Solidification on the in vitro Solubilisation of Blonanserin Loaded Supersaturated Lipid-Based Oral Formulations. / Moller, Amalie; Schultz, Hayley B.; Meola, Tahlia R.; Muellertz, Anette; Prestidge, Clive A.
In: European Journal of Pharmaceutical Sciences, Vol. 157, 105640, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Influence of Solidification on the in vitro Solubilisation of Blonanserin Loaded Supersaturated Lipid-Based Oral Formulations
AU - Moller, Amalie
AU - Schultz, Hayley B.
AU - Meola, Tahlia R.
AU - Muellertz, Anette
AU - Prestidge, Clive A.
PY - 2021
Y1 - 2021
N2 - Supersaturated silica-lipid hybrids have previously demonstrated improved in vitro solubilisation and in vivo oral bioavailability of poorly water-soluble drugs, however were only fabricated using a single lipid (LFCS type I formulations) and were not compared to their liquid precursors. This study investigated the influence of lipid formulation classification (type I vs. type II vs. type IIIA/SNEDDS) and physical state (liquid LBF vs. solidified with silica) on the in vitro solubilisation of the poorly soluble, weak base, anti-psychotic drug, blonanserin (BLON), from a supersaturated lipid-based formulation (LBF).Stable liquid supersaturated LBF were fabricated using BLON (loaded at 150% of its equilibrium solubility), and solidified through encapsulation within porous silica microparticles at a 1:1 ratio. Their physicochemical properties and in vitro solubilisation during lipolysis were compared.Supersaturated BLON was encapsulated in the non-crystalline form. All supersaturated LBF improved the solubilisation of pure BLON during lipolysis regardless of their lipid formulation type or their physical state (1.7- to 13.4-fold). SNEDDS achieved greater solubilisation than the type II formulations (1.4- to 1.7-fold). Furthermore, the liquid precursors achieved greater solubilisation than the silica solidified formulations (4.5- to 5.7-fold). Additionally, in an attempt to increase BLON solubilisation, a spray-dried SNEDDS and dual-loaded solidified super-SNEDDS solidified with silica pre-loaded with BLON was developed, however did not significantly improve solubilisation.Liquid SNEDDS were identified as the optimal oral supersaturated LBF strategy for BLON based on in vitro lipolysis studies. Solidification of LBF using silica is a viable strategy for improving stability, however for drugs such as BLON, solidification may impede in vitro release and solubilisation.
AB - Supersaturated silica-lipid hybrids have previously demonstrated improved in vitro solubilisation and in vivo oral bioavailability of poorly water-soluble drugs, however were only fabricated using a single lipid (LFCS type I formulations) and were not compared to their liquid precursors. This study investigated the influence of lipid formulation classification (type I vs. type II vs. type IIIA/SNEDDS) and physical state (liquid LBF vs. solidified with silica) on the in vitro solubilisation of the poorly soluble, weak base, anti-psychotic drug, blonanserin (BLON), from a supersaturated lipid-based formulation (LBF).Stable liquid supersaturated LBF were fabricated using BLON (loaded at 150% of its equilibrium solubility), and solidified through encapsulation within porous silica microparticles at a 1:1 ratio. Their physicochemical properties and in vitro solubilisation during lipolysis were compared.Supersaturated BLON was encapsulated in the non-crystalline form. All supersaturated LBF improved the solubilisation of pure BLON during lipolysis regardless of their lipid formulation type or their physical state (1.7- to 13.4-fold). SNEDDS achieved greater solubilisation than the type II formulations (1.4- to 1.7-fold). Furthermore, the liquid precursors achieved greater solubilisation than the silica solidified formulations (4.5- to 5.7-fold). Additionally, in an attempt to increase BLON solubilisation, a spray-dried SNEDDS and dual-loaded solidified super-SNEDDS solidified with silica pre-loaded with BLON was developed, however did not significantly improve solubilisation.Liquid SNEDDS were identified as the optimal oral supersaturated LBF strategy for BLON based on in vitro lipolysis studies. Solidification of LBF using silica is a viable strategy for improving stability, however for drugs such as BLON, solidification may impede in vitro release and solubilisation.
KW - Lipid-based formulation
KW - oral drug delivery
KW - porous silica
KW - blonanserin
KW - lipolysis
KW - supersaturation
KW - DRUG-DELIVERY-SYSTEMS
KW - WATER-SOLUBLE DRUGS
KW - POROUS NANOSTRUCTURE
KW - VIVO PERFORMANCE
KW - DIGESTION
KW - CLASSIFICATION
KW - ESTABLISHMENT
KW - TESTS
KW - STRATEGIES
KW - CARRIERS
U2 - 10.1016/j.ejps.2020.105640
DO - 10.1016/j.ejps.2020.105640
M3 - Journal article
C2 - 33189902
VL - 157
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
SN - 0928-0987
M1 - 105640
ER -
ID: 256163061