| Controlled drug release is one of the most important tasks in pharmaceutics. Great progress has been made in this field, and many materials and systems have been developed to satisfy the requirements for controlled delivery of a variety of drugs and vaccines. In these systems, the biodegradable polymeric microparticle formulation is one of the most important drug delivery systems.The aim of this paper is preparing aspirin-loaded microspheres, using polylactide (PLA) and its copolymer as the matrices. Different preparation methods were evaluated to prepare aspirin containing microspheres with high drug entrapment efficiency and desirable drug release behaviors. The microspheres obtained were characterized by FT-IR, DSC and SEM, and in vitro drug release was studied as well. Major work and the results of this paper are :1. Preparation of aspirin-loaded PLGA microspheres using O/W, O/O solvent evaporation techniques and O/W emulsion-phase separation technique. Becasue aspirin can be dissolved in water (0.33 g/100 ml), the loading efficiency of microspheres prepared by O/W solvent evaporation technique was very low. Changing polymer/aspirin ratio, increasing the polymer concentration and introducing acetone into the inner oil phase resulted in no increase in the loading efficiency. Most of aspirin was diffused into outer water phase during the course microsphere preparation, and the maximal loading efficiency is about 15%. Decreasing the volume of outer water phase or using O/W emulsion-phase separation technique almost has no effect on the aspirin entrapment efficiency. Consequently, O/O solvent evaporation technique was utilized and similar results were observed, increased aspirin solubility as span 80 was added into outer oil phase might be responsible for these results, and maximal entrapment efficiency was 24.8% in this case. Aspirin crystal, which was separated form the micro-droplet of inner oil phase, was observed during the process of solvent evaporation and this might contribute to the poor entrapment efficiency.2. Aspirin/β - CD and aspirin/HP- β - CD inclusion complexs were prepared using saturated aqueous solution method and freeze-dry technique. The complexs with 1/1 molar ratio were characterized by ultraviolet spectroscopy (UV), FT-infraredspectroscopy (FT-IR) and differential scanning calorimetry(DSC). The solubility and stability of aspirin increased when the inclusion complexs were formed.3. Preparation of aspirin/p - CD or aspirin/HP-β - CD inclusion complex containing microsphere based on PLA and its copolymers using S/O/O or W/O/O solvent evaporation technique respectively. By inclusion aspirin into P - CD, microspheres with high entrapment efficiency (almost 100%) was obtained and no aspirin crystal was observed during the process of solvent evaporation. However, for the limitation of the size of inclusion complex, the loading efficiency decreased when particle size was less than l00μm. The solubility increased dramatically when aspirin was included in HP-β - CD, and microspheres were prepared utilizing W/O/O emulsion solvent evaporation technique accordingly. The particle size of microspheres obtained was less than 20μm and a more sustained in vitro release behavior was observed. For the existence of a dynamical equilibrium between aspirin and its inclusion, aspirin could diffuse across inner oil phase into outer oil phase and the loading efficiency was about 60%.4. Comparison of the in vitro release behaviors of aspirin loaded microspheres prepared with different methods or polymers. The polymer and the ratio of polymer with aspirin or inclusion complexes had a significant effect on the drug release behavior. Adding acetone (O/W solvent evaporation technique) and DMC (W/O/O solvent evaporation technique) into inner oil phase could affect the density of the microspheres. Aspirin released from the inclusion complexs loaded microspheres was more stable than individual aspirin loaded microspheres. |
PDF Full Text Request