仿制药高端制剂国际化的研发策略--吴传斌.ppt

This is a typical example on aging issue of aqueous film coating. ? Many scientists found that drug release rate from coated dosage form could be changed after stored at room temperature or high temperature. This slide shows the influence of curing time at 40 ?C on the release of theophylline from beads coated with 12% Eudragit RS30D. The curing of coated beads at 40 ?C for 2 days showed a significantly slower release of the drug. This observation indicate the importance of temperature and time effects on complete film formation when coalescence is a slow process. Another issue in aqueous film coating is agglomeration and tackiness. During coating process, some agglomeration of several pellets can happen, especially at higher operation temperature and higher plasticizer level in coating formulation. The agglomeration of coated dosage form during coating and curing steps will also result in unstable drug release rate and trouble of coating process. For coating applications, a low tackiness is desirable. Because It will be an easier handling of the coating process and it also reduce the process time. How to avoid the tackiness? Traditional anti-tacking methods include: The traditional technique to avoid agglomeration is use of anti-tacking agent. Talc is frequently used as an anti-tacking agent. However, it could result in sedimentation in tanks, nozzle clogging and incompatibility with certain drugs. ? GMS is another good anti-tacking agent. It can be used at a much lower concentration and can be added to the polymer dispersion as an emulsion, therefore avoiding potential sedimentation problems. However, the properties of coated dosage forms may be changed when processing temperature is higher than 65 ?C since the melting point of GMS is 65 ?C. ? HPMC overcoat show great promise to avoid the tackiness problem but it is sometime subjected to the patent restriction. The effect of storage time at 23C on the dissolution rate of ibuprofen from coated beads is