For a drug with low bioavailability, a matrix tablet with liquid permeation enhancer (Labrasol) was formulated. Factorial design was used to evaluate the effect of three formulation factors: drug percentage, polymer type (Methocel K100M or Eudragit L 100-55), and tablet binder percentage (Plasdone S-630) on tablet characteristics. Tablets were prepared by direct compression and characterized. Compressibility index values ranged between 15.90% and 29.87% and tablet hardness values from 7.8 to 29.78 Kp. Eudragit-containing formulations had better compressibility index values with higher tablet hardness. Time for 75% of drug release (T75) was calculated, and formulations containing Eudragit L 100-55 had faster release rates than tablet formulations with Methocel K100M. Formulations with Methocel K100M fit well in the Higuchi model as indicated by their R2 values (>0.98). Among all the formulation factors studied, polymer type displayed the highest and statistically significant effect on compressibility index, tablet hardness, and dissolution rate. Statistical design helped in better understanding the effect of formulation factors on tablet characteristics important for designing formulations with desired characteristics.