Interactions between mesocellular foam silica carriers and model drugs constructed by central composite design

Abstract

In this work, the influences of the four factors including hydrogen bond acceptor (HBA) count (X₁), MCF pore size (X₂), drug loading degree (X₃) and dissolution stirring rate (X₄) as well as their cross-interactions for drug release behaviors were investigated. The factors were chosen from all drug release aspects consisting of drug, carrier, formulation and dissolution, respectively. A five-level four-factorial composite central design (CCD) was performed for the investigation with cumulative release over 1 h (Y₁), cumulative release over 24 h (Y₂) and rate constant k (Y₃) as three dependent response variables. A series of MCFs (4MCF, 7MCF, 12MCF, 17MCF and 22MCF) with various pore diameters were synthesized to be applied as drug carriers, and five BCS II drugs including disulfiram (DIS), loratadine (LOR), celecoxib (CEL), metronidazole (MET) and nimodipine (NIM) were selected as model drugs possessing different numbers of HBAs. The morphologies, structures and pore size distributions of the MCFs were systematically studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption analysis (BET), and the drug loading samples were analyzed using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The release behavior was examined by in vitro dissolution. The interactions between the model drugs and the MCFs were analyzed in detail using response surface plots. The present work may provide some scientific references for selecting the appropriate mesoporous silica carrier for a specific drug.

Keywords: Central composite design; Drug release; Mesocellular foam silica.