Blends of hydrophobic and swelling agents in the swelling layer in the preparation of delayed-release pellets of a hydrophilic drug with low MW: Physicochemical characterizations and in-vivo evaluations

In this study,a hydrophobic material,ethylcellulose,which was used as its aqueous suspension Surelease^(®),was combined with a swelling agent as the swelling layer to prepare delayed-release pellets for Danshensu,which is a hydrophilic drug with low MW.A rupturable,delayed-release pellet consists of a drug core,a swelling layer containing a swelling agent(cross-linked sodium carboxymethyl cellulose)with a hydrophobic agent(Surelease^(®)),and a controlled layer composed by an insoluble,water-permeable polymeric coating(aqueous ethylcellulose dispersions)was developed in a fluidised bed.Results showed that blending Surelease^(®)into the swelling layer could effectively extend the release of Danshensu from the pellets,which may be attributed to the slowed swelling rate by reduction of water penetration and improvement of mechanical integrity of the swelling layer.Drug in the delayed pellets showed sustained release in beagle dogs after oral administration with comparable in-vivo exposure to the uncoated drug pellets.In conclusion,blends of hydrophobic and swelling agents in the swelling layer in doublemembrane pellets could achieve a delayed drug-release profile in vitro,as well as delayed and sustained absorption in vivo for highly soluble,low-MW drug.The present study highlighted the potential use of a delayed-release system for other hydrophilic,low-MW drugs to meet the formulation requirements for chronopharmacological diseases.

Synthesis of Highly ordered Large Size Mesoporous Silica and Effect of Stabilization as Enzyme Supports in Organic Solvent

FSM 16, MCM 41 and SBA 15 types of hexagonal mesoporous silica with a highly ordered 2 dimensional structure were synthesized by using different silicon sources and surfactants. In the 2 dimensional silicate framework, pore size can be uniformly controlled by the combined use of the surfactants having different alkyl chain lengths and the swelling agents(triisopropyl benzene). The pore diameter of FSM 16 and MCM 41 can be expanded to be 10 nm, SBA 15 to be 15 nm. The crystal regularity was decreased with the increase of the pore diameter. In FSM 16 derived from kanemite(silicon source) and MCM 41 from water glass, their anionic characteristics on the pore wall may be stronger than those of SBA 15 derived from oligomeric tetramethoxysilane(TMOS). We have successfully used FSM 16 and MCM 41 to immobilize the enzyme having cationic residues below isoelectric point. The level of adsorption of enzymes in FSM 16 and MCM 41 was relatively high, but was low in SBA 15 support. The mechanism of enzyme to be adsorbed in mesoporous silica was suggested to be the ionic interactions. In aqueous solutions, horseradish peroxidase(HTP) was immobilized in FSM 16 with 8.9 nm mesopores and the highest loading amount(183 mg/mg FSM) was obtained, but for the FSM 16 of pore diameter 30 nm only an amount of 28 mg/mg FSM was obtained. The catalytic activity in the organic solvent was high when HRP was immobilized in FSM 16 and MCM 41, but it was low in case of SBA 15.