The present study reports on the production of low molecular weight heparin (LMWH) loaded polymeric microspheres for delivery via the oral route. The microspheres were prepared by the spray-drying technique using Eudragit ® as the polymer. The objective of this study was to examine extensively the influence of formulation and process variables on the characteristics of the microspheres prepared. The effects of various experimental parameters such as polymer concentration, inlet temperature, and liquid feed flow rate on particle morphology, particle dimensions, and production yields were evaluated by means of experimental factorial designs. Electron microscopy, moisture content analysis, and fractal dimensional analysis were employed to characterize the microspheres. The inlet temperature and polymer concentration had the greatest effects on the production yield. Results showed that the polymer concentration affected the dimensions of the microspheres. Drug-loaded microspheres were spherical in shape and had a smooth surface with sizes ranging between 19–60 μm. Production yields were above 50% under most of the operating parameters studied. The selection of appropriate parameters yielded spray-dried microparticles characterized by smooth morphology and narrow dimensional distribution.