Study On Matrix-type Polymer Based Drug Sustained Release System

Polymeric materials play an important role in drug controlled release system. A lot of methods have been developed in order to achieve good "modulation" on their drug delivery performances so as to expanding polymer use in pharmaceutics. Biodegradable polymer is becoming the research trend, but non-biodegradable polymer also has many merits and is not replacable. So it is still meaningful to study both of them. Moreover, the influence of material properties on drug release behavior and the mechanism of drug delivery were still waiting further investigation. Therefore, in our research, several typical kinds of polymeric biomaterials, such as biodegradable polyester, hydrophilic protein, non-biodegradable polymethacrylates and organic/inorganic composites, were selected as drug carriers and were modified with different methods in order to gain well controlled release performance. All our drug delivery systems belong to matrix devices since it is one of the most frequently used systems. The mechanism of drug delivery and performances of those modified materials were studied. The main research content and results are as follows.Phoshorylcholine end-capped Poly-e-caprolactone (PC-PCL) was blended with Poly-e-caprolactone (PCL) in different ratio. The drug release behavior of the blends was investigated. The ibuprofen dispersion state in the microspheres was studied by DSC and XRD. The effect of the content of PC-PCL as well as drug loading in the matrix, and the molecular weight of PCL on the release behavior of the blend system have been investigated. It was found that ibuprofen was molecularly dispersed in the matrix as an amorphous form. The drug release rate increased with the increasing PC-PCL content because of its better hydrophilicity and degradation. Moreover, the drug release rate can be tuned by drug loading in the matrix and the molecular weight of PCL.Biodegradable gelatin is bio-adhesive but has poor sustained-release property when it is used as carrier for small molecular weight of drug because of the excessive high hydrophilicity. PCL, which has good sustained-release performance but was poor in bio-adhesion, was selected to enhance the delivery performance of gelatin in our research. As presented in the third chapter of this thesis, Gelatin films containing ibuprofen-loaded poly-e-caprolactone (PCL) microspheres have been developed in consideration of the complementary characteristics of the two components. The microspheres were obtained using an oil-in-water (O/W) emulsion solvent evaporation technique and then the films were formed by a cross-linking reaction. The surface morphology of microspheres was examined by SEM and the particle size and size distribution were measured with a laser diffraction particle size analyzer. At the same time, the water adsorption of prepared films was also measured. The results indicated that drug release rate was strongly influenced by water adsorption of films which was affected by preparation conditions. Both of the molecular weight of PCL and the kind of emulsifiers would influence the encapsulation efficiency and morphology of microspheres and thus affect drug release behavior. Most of the drug molecules that were encapsulated should diffuse through two levels of structural hierarchy: the primary microspheres consisted of PCL chains, and the secondary network consisted of crosslinked gelatin chains. This new system demonstrates better sustained-release property than pure gelatin.Poly (methyl methacrylate) (PMMA) is a kind of hydrophobic and biocompatible materials. Its drug release rate is rather slow for its higher glass transition temperature. In Chapter Four, a series of polymers with various Tg were prepared by copolymerizing butyl methacrylate (BMA) with MMA. The influence of drug loading on Tg of PBMA was also studied by DSC. The effect of Tg on drug release behavior was also investigated. The results indicated that with the increase of BMA component, the Tg of copolymers was decreased, and thus the drug release was accelerated. The diffusion coefficient of drug would steeply increase when Tg lowered than or closed to release temperature. But the effect of Tg weakened very quickly when the temperature is higher than the temperature of the release media. It was also found that drug release rate was affected by drug loading. The more drug loaded, the faster the drug release. The drug release rate of this system can be finely tuned by the ratio of BMA and MMA in copolymers and the drug loading in matrix.Polymer modification can not only using organic materials, but also introducing inorganic component into polymers to form organic/inorganic compound. In Chapter Five, we prepared PMMA/silica compounds by sol-gel method. The structure and morphology of the composite samples were studied by FTIR and SEM. The effect of the contents of silica and 3-trimethoxysilyl propyl methacrylate (MSMA), a silane coupling agent on drug release performance was also evaluated using aspirin as a model drug. The results indicated that in PMMA/silica matrix, the drug release kinetic followed Fickian diffusion. The drug release rate increased with the increasing content of silica by increasing interface area between inorganic and organic phases, while the release rate decreased with the increasing content of coupling agent because of the improvement of interfacial adhesion between polymer matrix and silica. The effect of phasic interface plays an important role only in matrix based on self-diffusion.