{\textcopyright}2014 Bentham Science Publishers.The present work aimed to develop and study the effect of HPMC on compression-coated floating - pulsatile delivery of Bisoprolol. Inner core tablet contains bisoprolol and a super disintegrant. Outer shell contains HPMC K4M and HPMC K100M as erodible layer along with a gas generating agent. Compression-coated tablet of bisoprolol with 120mg HPMC K4M (B2) showed a lag time of 3.40±0.1 hrs with 99.81% drug release. Whereas 110mg HPMC K100M (B5) showed a lag period 4.0±0.1 hrs with 98.91% drug release. A 32factorial design was applied. HPMC K4M CR and K100M were independent variables whereas drug release, lag time at 4 hrs and swelling index were dependent variables. To understand the interaction of independent variables on dependent variables three dimensional surface response plots were drawn. The responses exhibited by batch F4 (55 mg HPMC K4M and 65 mg K100M) showed lag time 4.20 hrs following the sigmoidal release pattern. Optimized batch F4 gave good in-vitro in -vivo correlation.