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 -