Studies On Property Of Sustained-release Enteric Film And Its Application

Aqueous polymer dispersion is a solid or semisolid spherical particles dispersion system, in which polymeric particles with a size between lOnm and1μm is dispersed in water. Compared to traditional film coating, the use of aqueous polymer dispersion for the coating offers various advantages, such as protected environment and shortened processing time.To obtain a particular, desired release profile that is adapted to the pharmacokinetic/pharmacodynamics characteristics of the drug, different formulation and processing parameters can be varied. However, the variation of these parameters is generally restricted. With the research and development of new drug, it is sometimes difficult to adjust optimized release kinetics. An interesting possibility to overcome the restrictions is to use blends of two types of polymers, which have different physico-chemical characteristics. By changing the polymer:polymer blend ratio, the properties of resulting film can effectively be altered and broad ranges of drug release patterns could be provided.The study is based on the use of blends of enteric polymer dispersion Eudragit(?)L30D-55and sustained-release polymer Kollicoat(?)SR30D. The polymer blends can provide drug sustained-release profiles that are triggered by the pH of the surrounding environment along the gastrointestinal tract. In the stomach (at low pH), both polymers are insoluble, whereas in the intestine (at high pH), the enteric polymer is soluble and a porous sustained-release coatings would come into being.Polymer blends dispersion of Eudragit(?)L30D-55and Kollicoat(?)SR30D was prepared by diluted with water and adding0.3%PVP as stabilizer. Free film of polymer blends was prepared by casting technique. Properties of the cast films including glass transition temperature, mechanical properties, permeability and solubility was investigated. Effect of polymer:polymer blend ratio on properties of the cast films was evaluated. Influence of additive on properties of the cast films was examined. As a result, with increasing SR30D content, properties of the cast films varied:glass transition temperature decreased; strength and stiffness of film weakened, tenacity enhanced; water vapor permeability remained at a certain level first and then increased; the rate as well as the extent of water uptake in0.1N HC1solution increased; weight loss of polymeric film in Phosphate buffer (PH6.8) decreased. Stiffness of free film weakened and water vapor permeability increased following with increasing amount of TEC. Glass transition temperature, mechanical properties, permeability and solubility can be altered by using different plasticizer. With the addition of insoluble additive such as talc, titanium dioxide, water vapor permeability and solubility decreased at different level.Pantoprazole sodium(PAZ-Na) was selected as a model drug to study polymer blends coating film. PAZ-Na containing pellet cores were prepared by extrusion spheronization method. PAZ-Na sustained-release enteric pellets were obtained by laying a HPMC water-soluble film coating and a L30D-55:SR30D polymer blends coating using a rotary fluidized-bed equipment. Pellets-type tablets were prepared by compressing the mixture of pellets with a size between24-30mesh and excipients. As a result, the formulation of pellet cores was optimized when antioxygen anhydrous sodium sulfite and metal ion complexing agent EDTA-2Na were added into water as adhesives with MCC:Mannitol (1:5) as fillers. The best gastro-resistance and desired release profile were obtained when the coating level of HPMC was16%, the coating level of L30D-55:SR30D (70:30) is30%. No more than5%drug degradation occured after pellets were exposed to0.1N HC1solution for2h.The sustained-release enteric pellets began to release the drug after10～20min and released completely after90min in phosphate buffer of PH6.8. The best excipients formulation of pellets-type tablets was MCC/lactose/PEG-6000(100:20:50) with pellets/excipients ratio was4:5. Drug release behavior, gastro-resistance test were examined to evaluate film damage during compression. Scanning electron microscopy(SEM) photos were taken to obtain a visual assessment of the pellets under compression. The results indicated severe film damage during compression was avoided and the compression process did not affect release profile of sustained-release enteric pellets disintegrated from tablets.In conclusion, free film or coating film of polymer blends offers favorable physical characteristics. Polymer blends dispersion of Eudragit(?)L30D-55and Kollicoat(?)SR30D can be used for R&D of modified-release enteric preparations.