Investigation of in-vitro release characteristics of NSAID-loaded polylactic acid microspheres

The intra-pulmonary delivery of non-steroidal anti-inflammatory drug-loaded PLA microspheres has potential utility in the treatment of inflammatory lung conditions such as asthma. Drug encapsulation efficiency and release kinetics depend upon a variety of parameters in the production process, all of which affect the properties of the microspheres produced. The release of piroxicam from PLA microspheres followed an apparently biphasic release profile. PLA microspheres containing indomethacin, however, exhibited kinetics which approached more closely to zero order release. The effect of microsphere production parameters upon these release profiles has been investigated. Results indicate that factors affecting the nature of the microsphere matrix have the greatest influence on release profiles. The use of halothane as organic solvent in the microsphere production increases the burst release effect. Residual halothane is known to be present in the microspheres, producing a less stable matrix, thus allowing much faster release of the drug. The nature of drug incorporated also appears to affect the nature of the microspheres matrix. Piroxicam-loaded microspheres possess a much more porous matrix than indomethacin-loaded microspheres, as evidenced by washing procedures. This difference could explain the difference in release profiles between the two types of microspheres.