Control and stability of drug release from diffusion pellets coated with the aqueous quaternary polymethacrylate dispersion Eudragit RS 30 D.

The addition within compatibility limits of the pore formers hydroxypropyl methylcellulose (HPMC) and hydroxy ethylcellulose (HEC) to coatings of the quaternary polymethacrylate dispersion Eudragit RS 30 D enables drug release to be controlled without problems. 20 and 15%, respectively, of these pore formers are suitable for release within 8 h of theophylline from pellets with a coating thickness of about 30 microns. A 10% addition of plasticizer, water soluble triethyl citrate (TEC) or water insoluble dibutyl phthalate (DBP), lowers the minimum film forming temperature (MFT) from 48 to 17 and 26 degrees C, respectively. The MFT is scarcely influenced by the pore formers. However, the plasticizers may modify the effect of the pore formers: HPMC is more effective in the presence of DBP. In spite of the preparation of the coatings at a bed temperature about 20 degrees C above MFT, the release from the diffusion pellets is not stable during storage. Only curing in an oven or in the fluidized bed up to a certain limiting release rate at 80 degrees C for 1 h results in stable products. Increased relative humidity allows reduction of the curing temperature. The water soluble additives polyoxy ethylene (PEG) and polyvinyl pyrrolidone (PVP) and insoluble additives are ineffective as pore formers.