Silica-based Hybrid Materials Preparation And Drug Controlled Release Applications

The purpose of this thesis is to design and prepare some silica-based materials to study the drug release mechanisms, to control the release of water-soluble drugs of small molecules, to raise the drug loading in the carrier materials, and at the same time to find an easy, flexible, and effective strategy to control the drug release.In order to understand the release mechanisms, the reactivity and release of acid-base indicators entrapped in silica and hybrid silica gels were studied. Tetraethoxysilane (TEOS), n-propyltriethoxysilane (PTES), and bis(trimethoxysilyl)hexane (TSH) were used as gel precursors. The experimental results suggest that adding the organosilanes lower the pore size and pore volume of the gels and therefore, suppress the indicator release, but do not present any obvious effects on the acid-base reactivity of the entrapped indicators. In general more indicators were found to release in basic solutions than in acidic solutions. For all the entrapped indicators in acidic solutions through the while release process, and in basic solutions at the beginning of the release, the indicator release was found to follow the sequence of TEOS Gel > TEOS/PTES Gel > TEOS/TSH Gel. The overall release process was found to be diffusion-controlled, and the release was mainly affected by the textural properties of the gels, the interactions between the gel matrices and the indicators, and the indicator solubility.In order to find a good recipe to effectively control the release of water-soluble drugs of small molecules, the controlled release of sodium salicylate (SS) from the gels derived from bis(trimethoxysilylpropyl)amine (TSPA) or the mixture of TSPA with tetraethoxysilane (TEOS) was investigated. The experimental results suggest that the release of SS can be easily controlled by adjusting the ratio between TSPA and TEOS. Increasing the ratio between TSPA and TEOS lowers the surface area and pore volume of the gels, while enhances the interactions between the drug and the gel matrix, therefore, reduces the release rate of the drug effectively. TSPA can dissolve in both water and common organic solvents. It was found to be a very convenient and effective precursor for the preparation of gels for controlled release of both hydrophilic and hydrophobic drugs, especially water-soluble drugs of small molecules.In order to raise the drug loading in the carrier materials, and at the same time to find an easy, flexible, and effective strategy to control the drug release, the controlled release of vitamin B1 (VB1, thiamine hydrochloride) from mesoporous silica tablets coated with a series of sol-gel films were investigated. The effects of organosilane type and concentration, coating time, drying temperature, and release media on VB1 release from the coated mesoporous silica tablets were examined comprehensively. VB1 release decreased with the increase in coating time and drying temperature. The experimental results show that drug release can be easily controlled by changing the organosilane type and coating time. The method used in this study appears to be an effective and flexible way to control drug release because of the high drug loading in the mesoporous silica carrier and the ease control of the release by manipulating the coatings.