The aim of this study was to develop a pH-independent extended release matrix tablet of minocycline HCl for the treatment of dementia. The matrix tablets were prepared by wet granulation technique using Eudragit L and S as release modifiers at different w/w ratios (1:0, 1:1 and 0:1) and PEO as a matrix former. In the case of the matrix tablet without any release modifiers, the drug release rate at pH 1.2 was much higher than that of pH 7.4. By adding the release modifier, the drug release rate at pH 7.4 increased close to that of pH 1.2 and the pH-independent release was obtained. In addition, it was shown that lubricants containing a divalent cation such as Mg stearate inhibited minocycline release in basic medium. Therefore, the incorporation of Eudragit L and S (1:1 ratio) as release modifiers and Na stearyl fumarate as a lubricant into PEO-based matrix tablets effectively produced pH-independent minocycline release profiles.