A Drug Release Model Constructed by Factorial Design to Investigate the Interaction Between Host Mesoporous Silica Carriers and Drug Molecules

AAPS PharmSciTech. 2019 Feb 26;20(3):126. doi: 10.1208/s12249-019-1340-0.

Abstract

A drug release model based on mesocellular foam silica (MCF) for Biopharmaceutics Classification System (BCS) II drugs was conducted. A three-level two-factorial factorial design was carried out for the exploration of the influence of the pore size of MCF (X1) and drug-loading degree (X2) for drug release behaviors. Cumulative release in 1 h (Y1), cumulative release in 24 h (Y2), and rate constant k (Y3) were selected as dependent response variables. A series of MCFs (7MCF, 12MCF, and 17MCF) with arithmetic increased pore diameters was synthesized as drug carriers. The morphologies and structures of MCFs and pore size distributions were detected by scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption analysis. With celecoxib as a model drug, nine drug-loaded samples were prepared and further characterized by differential scanning calorimetry and X-ray diffraction analyses. The release behavior was examined by in vitro dissolution. Factorial design results demonstrated that cumulative release in 1 h and the rate constant k were mainly affected by X2, while cumulative release in 24 h was influenced by both X1 and X2. Furthermore, quadratic equations of Y1, Y2, and Y3 were conducted, respectively. This work was expected to provide some scientific references for designing specific drug delivery models with mesoporous silica carrier.

Keywords: drug release; factorial design; mesocellular foam silica.

MeSH terms

  • Biopharmaceutics
  • Calorimetry, Differential Scanning
  • Celecoxib / chemistry
  • Drug Carriers*
  • Drug Design
  • Drug Liberation
  • Factor Analysis, Statistical
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Models, Chemical
  • Pharmaceutical Preparations / chemistry*
  • Porosity
  • Silicon Dioxide*
  • Solubility
  • X-Ray Diffraction

Substances

  • Drug Carriers
  • Pharmaceutical Preparations
  • Silicon Dioxide
  • Celecoxib