| In this paper, Diclofenac Sodium was chosen as model drug andβ-CD was used as material to prepare drug-β-CDP microspheres(MS). Furthermore, the swelling properties of the polymer microsphere and drug release behavior in vitro and their release mechanism were deeply studied.In the study of preparation method,β-CDP MS was first prepared by the technique of inverse emulsion polymerization. And the synthesis ofβ-CDP MS was optimized by using the single factor investigation and the orthogonal test to test the effect of various factors on results. The criteria to evaluate the MS included the appearance, particle's size and yield. Optimal formulation was chosen and MS were formed with good quality. The results showed that the stirring rate and emulsifier mainly affect the particle's size and yield separately. The test technological conditions were: kerosene as the oil phase, n(ECH):n(β-CD)=15:1, crosslinking time=1.5h, crosslinking temperature=30℃, Span80:Tween20=3:1, emulsion time is 7h, emulsion temperature=50℃, the stirring rate is 900r/min. The repeatability of the technology was precise.β-CDP MS were shape spherical, size equality, regular in morphology, surface smooth, with the mean diameter of 40.45±3.8μm and the span of 1±0.15(n=5). Prepared microsphere reserved the cavity structure ofβ-CD and with a high content of it. Theβ-CDP MS had a unconsolidated, honeycomb, cross-linking three dimensions, reticular internal structure. They also had a good liquidity and high water-absorbent.After establishment of optimal formulation of synthesizingβ-CDP MS, we prepared drug-β-CDP MS with three methods. One was direct method, and the other one was inclusion compound, the third was infusion method. The experimental results indicate that: first, drug content percent of the infusion method was higher than the direct method and inclusion compound method. Second, drug crystals were seen on the surface of drug-β-CDP MS by the direct method and inclusion compound method.In the study of the swelling properties of the polymer microsphere, the swelling rate of the polymer microsphere increased with the increasing of the buffer solution pH and its concentration in different conditions. The higher the drug loaded, the faster the drug released, but the swelling speed controlled by ion-dependent swelling mechanism was limited in the high concentration buffer solution. Then, a mathematical model of drug release was established, based on the diffusion law. We applied elastomer equations about stress-strain relationship, De and Sw to describe the water-absorbed of polymer and the drug release process, taking into account the material expansion caused by solvent infiltration.In the study of drug release from MS in vitro, commonly used dialysis method was studied comprehensively. In this experiment, DFS-β-CDP MS was the key point, and studied the effect of various factors (preparation method, pH of media, solution volume inside the dialytic-bags, drug content percent and particle's size) on drug release behavior. The experimental results indicate that: first,β-CDP MS had a sustained release effect on DFS, achieving 24h. This indicated that cavity structure ofβ-CDP MS intercalated with drug to make it release slowly; second, for DFS-β-CDP MS, all the factors, especially the particle's size, had an effect on drug release behavior.The article also valuated the results of drug release from MS in vitro with two mathematical models. Firstly, empirical and half-empirical mathematical model were used to prove that release of DFS-β-CDP MS according with first-order release and Korsmeyer-Peppas model. The mechanism of drug release was bone solution and diffusion mainly. Secondly, diffusivity (D) was calculated by model of"radial diffusion in a sphere"(Crank).
|
PDF Full Text Request