This research aims were to formulate a floatable acyclovir hollow-microspheres and control the release of drug using polymer Eudragit RS PO for prolongation of gastric residence time. The floating microspheres were prepared by emulsification solvent evaporation technique. The ratio between drug and polymer in Formula 1, 2, and 3 were 1: 3; 1: 3.5; and 1: 4, respectively. Drug-excipients compatibility were evaluated using Fourier Transform Infra- Red spectrometry, and particle size distributions were characterized by optical microscopes; while shape and surface morphology were observed by scanning electron microscopy. Dissolution test of acyclovir from the microspheres was carried out using paddle method USP Dissolution Apparatus. Density and buoyancy test were performed by using standard procedures. Increasing of polymer concentrations increased the average particle size. The average particle size of Formula 1, 2, and 3 were 26.09, 33.08, and 37.92 μm, respectively. The higher the polymer concentrations, the higher the percentage of drug entrapment. The highest buoyancy and percentage of entrapment observed in Formula 3 were 76.33% for 6 hours and 72.32%, respectively. It was indicated that the Formula 3 has the highest ability to float of. The percentage of drug dissolved for 6 hours from Formula 1, 2, and 3 were 99.95 ± 0.43; 101.54 ± 0.64 and 100.26 % ± 0.64, respectively. The higher the concentration of the polymer used, the slower the dissolution rate.
