Theophylline radial release from cellulose derivatives with different substitution type (HPMC K4M, HPC H, MC A4M) matrix tablets has been modulated by the introduction of a new inert polymeric excipient, at different proportions (75, 50, 25%). The new polymer was hydroxypropylcellulose-methyl methacrylate (HCMMA), which was dried either in a vacuum oven (OD-HCMMA) or freeze-dried (FD-HCMMA). MC A4M and its mixtures presented the best compaction properties results, especially mixed with FD-HCMMA, according to 100% mixtures. Only high levels of HCMMA (75%) in the matrices showed interesting differences to drug release modulation. Also, at this proportion (75:25), the HPC H mixtures presented the highest differences in relation with OD or FD HCMMA respect to the other cellulose polymers. HPMC K4M and HPC H mixtures showed a combination of diffusion and erosion release mechanisms. The last one was nearly negligible in MC A4M mixtures, according with its highest diffusion rate constant values, and the absence of hydroxypropyl substituents. Only HPMC K4M mixtures presented a diffusion front that moves outwards, while HPC H and MC A4M moves inwards. The modulation of theophylline radial release was obtained using a high percentage of HCMMA, and the use of two cellulosic ethers, one of them with just one type of substituent (MC A4M or HPC H) and the other with two types of substituent (HPMC K4M). Another possibility is changing the HCMMA copolymer (OD or FD) in the 75/25 mixture with HPC.