Evaluation of poly(DL-lactide-co-glycolide) nanoparticles as matrix material for direct compression

The objectives of this study were to prepare matrix tablets with poly(DL-lactide-coglycolide) (PLGA) particles and drug by direct compression and to evaluate the effects of altering the PLGA particle size, compression pressure, drug species and the PLGA nanoparticle content on compressibility and compactibility. In addition, the release rates of drugs from matrix tablets were evaluated and the release mechanism will be discussed. PLGA nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method, while PLGA microparticles were prepared by a solvent evaporation method. Tablets were prepared by direct compression. The tablet strength, porosity, release profile, molecular weight and tablet weight were examined. The compressibility of PLGA particles tended to become slightly poorer with decreasing particle size, while the nanoparticles gave significantly better compactibility compared to microparticles. The incorporation of nanoparticles was more effective in retarding drug release than microparticles. The addition of nanoparticles improved the compressibility and compactibility regardless of drug species, and their release rates were dependent on the solubility of drugs. At low nanoparticle content (20%), the drug was completely released within a period of 20 h, while the drug release showed a biphasic release pattern at higher nanoparticle contents. Analysis of the release mechanism indicated that the first phase of drug release corresponded to the diffusion theory, while the second phase seemed to be due to degradation of PLGA. We conclude that PLGA nanoparticles provide significant compactibility and could be useful as a retardant material for matrix tablets by direct compression.