Preparation And In Vitro Release Property Of Lovastatin Poly (Lactic Acid) Microspheres

Biodegradable microspheres which encapsulate drugs especially polypeptides/proteins with natural or chemosynthetic biodegradable polymer, are one of novel sustained and controlled release drug delivery systems. It can improve the safety and effectiveness of medication through changing drug dynamic behavior in human body, and sustain a more longer effect, decrease the times of administration, so biodegradable microspheres have good characteristics of sustained and controlled release and targeting characteristics. The most studied biodegradable polymer is PLA as carrier materials of microspheres.Lovastatin is used to decrease the content of serum cholesterol in clinic. However, the half-Life of Lovastatin in vivo is relatively short, the range of blood drug concentration change is very big after taking Lovastatin ordinary preparation, the phenomenon of sudden release is very obvious. Our study used polylactic acid as carrier materials to prepare Lovastatin sustained-release microspheres with the purpose of maintaining an effective concentration of Lovastatin in vivo and extending the drug treating time. The main work is follows: 1. Using solvent evaporation extraction method to prepare lovastatin microspheres, selecting the optimum process with orthogonal test, and analyzing factors that influence the technology. Investigate the microspheres' characteristics such as surface morphology and average diameter with scanning electron microscope, and calculate drug load rate and entrapment rate. Dialysis method was used to study the drug release property. Microspheres prepared by the optimum process were round and smooth. For microspheres made of PLA(Mr=50000), the average diameter was 65.8μm, load efficiency was 32.28%, encapsulation rate was 81.81%; for microspheres made of PLA(Mr=30000), the average diameter was 63.3μm, load efficiency was 27.66%, encapsulation rate was 60.84%; in vitro accumulative release rate was 40.96% and 34.81% in 10 days respectively at 37℃. Drug released from microspheres was through diffusion mechanism and dissolution mechanism. The release profile fit for the Higuchi Equation.2. Studied the effect of parameters on physicochemical properties of microspheres and the drug release characteristics in vitro. Investigate four factors that have the biggest influence:the concentration of PLA,the concentration of gelatin,feed ratio and water-oil ratio. These factors have different effect on average diameter,load efficiency and encapsulation rate. The drug release rate also related to these factors. To increase the load efficiency and encapsulation rate of microspheres, mixed solvents was applied in organic phase and electrolyte was added into external water phase. The results showed that organic solvent that can mix and dissolve with water increased load efficiency and encapsulation rate; the addition of inorganic salt also obtained the same results.3. Using three types of polylactides materials:PLA,PLGA,PELA, which have different hydrophilicity to prepare lovastatin microspheres, comparering their drug loadings,encapsulation efficiency,and in vitro release behavior. The results show that microspheres prepared with PLA and PLGA are round and smooth, PELA microspheres have irregular shape. PELA microspheres also have the highest drug loadings,encapsulation efficiency and drug release rate, because PELA have the highest hydrophilicity. The conclusion is that:the drug loadings,encapsulation efficiency and drug release rate increased with the enhancement of carrier materials'hydrophilicity.