| In this paper, Diclofenac Sodium, Sulfamethoxazole, Paracetamol and Ciprofloxacin Hydrochloride were chosen as model drug andβ-CD was used as material to prepare drug-β-CDP microspheres(MS). Furthermore, 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: n(EPI):n(β-CD)=15:1; crosslinking temperature=30℃; crosslinking time=1.5h; Span80:Tween20=3:1; kerosene as the oil phase; emulsion temperature=50℃;emulsion time is 6h; the stirring rate is 800r/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 102.14±4.6μm and the span of 1±0.14(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. In the study of thermal stability, three method were used to calculate E a, n , t1 /2 and k. The results indicated thatβ-CDP MS had a good thermal stability. Results of three methods were basically consistent: Ea=120～170 kJ·mol-1, n=1, A=7.4×1012, k298=1.305×10-16s-1, k273=3.037×10-19s-1, t 12/928=1.68 hundred million years and t 12/723=723.67 hundred million years. The storage period ofβ-CDP MS was very long in 298K and 273K. Thermal decomposition reaction mechanism ofβ-CDP MS belonged to random successive nucleation.After establishment of optimal formulation of synthesizingβ-CDP MS, we prepared drug-β-CDP MS with two methods. One was infusion method, and the other one was direct method. The experimental results indicate that: first, drug content percent of the infusion method was higher than the direct method; second, drug content percent was affected by acting force between drug andβ-CD/β-CDP MS; third, drug crystals were seen on the surface of drug-β-CDP MS by the direct method.In the study of drug release from MS in vitro, commonly used dialysis method was studied comprehensively. In this experiment, drug release behavior in vitro of four drug-β-CDP MS by the infusion method was studied. Then 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, solution volume outside 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 four drugs, especially for DFS and Sulfamethoxazole, achieving 24h and 20h respectively. This indicated that cavity structure ofβ-CDP MS intercalated with drug selectively 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 and SMZ-β-CDP MS according with first - order release and Korsmeyer-Peppas model. The mechanism of drug release was diffusion mainly. Secondly, diffusivity (D) was calculated by model of"radial diffusion in a sphere"(Crank). Thirdly, dialysis release drug models were used. Mathematic formula were deduced and the permeation constant (K) of free drug through dialysis membrane was determined. Then the drug release kinetics and drug release rate constants (km or km,) were achieved.
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