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...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.展开更多
Most seed gums have been widely used in oral and topical pharmaceutical formulations, cosmetics, and food products because of their hydrophilic properties. Gums from Tamariudus indica and Cassia fistula seeds were che...Most seed gums have been widely used in oral and topical pharmaceutical formulations, cosmetics, and food products because of their hydrophilic properties. Gums from Tamariudus indica and Cassia fistula seeds were chemically modified by carboxymethylation to improve their functionalities. The objective of the present study was to characterize and evaluate crude and carboxymethylated gums from T. indica and C. fistula seeds to achieve the controlled-release of diclofenac sodium(DS) in matrix tablet form. Both crude and carboxymethylated gums were characterized by Fourier transform infrared spectroscopy, Xray diffraction, and scanning electron microscopy. The results revealed that the gums were successfully modified by carboxymethylation and that the modified gums were amorphous in structure and had better flow properties. The carboxymethylated gums from both plant seeds did not exhibit cytotoxicity at concentrations lower than 0.5 mg/ml. All gum samples used as polymeric controlled-release agents were formulated into DS matrix tablets. Hardness and thickness tests were conducted as in-process tests. Drug content estimation and in vitro drug release studies were carried out to evaluate the matrix tablets. Increasing the concentration of gums increased compression time and hardness while it reduced the thickness. Furthermore, the results fitted well with the Korsmeyer–Peppas model. Moreover, the DS tablets were found to release the drug by super case II transport(relaxation). In summary, the carboxymethylated gum from T. indica and C. fistula seeds is an excellent, naturally sourced gum with high physicochemical and functional qualities, and can potentially be used in pharmaceutical applications as a disintegrant, diluent, and drug release-controlling agent.展开更多
基金Financial support was provided by a research grant from the University of Macao(Research Grant RG085/09-10S/ZY/ICMS and UL016/09-Y4/CMS/WYT01/ICMS).
文摘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.
基金the Higher Education Research Promotion-National Research Universities(HERP-NRU)for financial support under grant no.2559A10862013
文摘Most seed gums have been widely used in oral and topical pharmaceutical formulations, cosmetics, and food products because of their hydrophilic properties. Gums from Tamariudus indica and Cassia fistula seeds were chemically modified by carboxymethylation to improve their functionalities. The objective of the present study was to characterize and evaluate crude and carboxymethylated gums from T. indica and C. fistula seeds to achieve the controlled-release of diclofenac sodium(DS) in matrix tablet form. Both crude and carboxymethylated gums were characterized by Fourier transform infrared spectroscopy, Xray diffraction, and scanning electron microscopy. The results revealed that the gums were successfully modified by carboxymethylation and that the modified gums were amorphous in structure and had better flow properties. The carboxymethylated gums from both plant seeds did not exhibit cytotoxicity at concentrations lower than 0.5 mg/ml. All gum samples used as polymeric controlled-release agents were formulated into DS matrix tablets. Hardness and thickness tests were conducted as in-process tests. Drug content estimation and in vitro drug release studies were carried out to evaluate the matrix tablets. Increasing the concentration of gums increased compression time and hardness while it reduced the thickness. Furthermore, the results fitted well with the Korsmeyer–Peppas model. Moreover, the DS tablets were found to release the drug by super case II transport(relaxation). In summary, the carboxymethylated gum from T. indica and C. fistula seeds is an excellent, naturally sourced gum with high physicochemical and functional qualities, and can potentially be used in pharmaceutical applications as a disintegrant, diluent, and drug release-controlling agent.
