The aim of this work was to prepare ascending release compression-coated(CC) tablets with paliperidone(PAL) using a simple manufacturing technique and short manufacturing process.The release behavior and mechanisms in...The aim of this work was to prepare ascending release compression-coated(CC) tablets with paliperidone(PAL) using a simple manufacturing technique and short manufacturing process.The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose(HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose(HPMCK100 M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points.Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1(core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.展开更多
A procedure to evaluate the quality consistency of generic drugs based on the impurity profile and the similarity analysis methods was presented in this paper. Nifedipine extended-release tablets from six generic fact...A procedure to evaluate the quality consistency of generic drugs based on the impurity profile and the similarity analysis methods was presented in this paper. Nifedipine extended-release tablets from six generic factories of China were used to evaluate the uniformity with the original drug in the study. The procedure includes: choice of chromatographic methods, data collection and conformity test, evaluation of intra-batch similarity of drugs, evaluation of generic drugs with the original drug and weighted similarity evaluation of generic drugs. The data were collected via high-performance liquid chromatography (HPLC), and then calculated by correlation coefficient, cosine, principal component analysis (PCA) and hierarchical clustering analysis (HCA). It is more suitable to use peak areas as the vector when calculating the similarity of impurity profile. After weighting the peak areas of the unspecified impurities in further evaluation of the generic quality, the generic level of different factories was differentiated and the best generic factory was picked out.展开更多
The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combinati...The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.展开更多
The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacroli...The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate(Compritol~?ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion-and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.展开更多
The objective of this study is to investigate the feasibility of using chitosanesodium alginate(CSeSA)based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables.Using tri...The objective of this study is to investigate the feasibility of using chitosanesodium alginate(CSeSA)based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables.Using trimetazidine hydrochloride(TH)as a water-soluble model drug,influence of dissolution medium,the amount of CSeSA,the CS:SA ratio,the type of SA,the type and amount of diluents,on in vitro drug release from CSeSA based matrix tablets were studied.Drug release kinetics and release mechanisms were elucidated.In vitro release experiments were conducted in simulated gastric fluid(SGF)followed by simulated intestinal fluid(SIF).Drug release rate decreased with the increase of CSeSA amount.CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found.On the other hand,a large amount of water-soluble diluents could modify drug release profiles.It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism.In conclusion,this study demonstrated that it is possible to design extended-release tablets of watersoluble drugs using CSeSA as the matrix by optimizing formulation components,and provide better understanding about drug release from CSeSA matrix tablets.展开更多
基金funded by National Natural Science Foundation of China (No.81673378)
文摘The aim of this work was to prepare ascending release compression-coated(CC) tablets with paliperidone(PAL) using a simple manufacturing technique and short manufacturing process.The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose(HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose(HPMCK100 M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points.Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1(core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.
文摘A procedure to evaluate the quality consistency of generic drugs based on the impurity profile and the similarity analysis methods was presented in this paper. Nifedipine extended-release tablets from six generic factories of China were used to evaluate the uniformity with the original drug in the study. The procedure includes: choice of chromatographic methods, data collection and conformity test, evaluation of intra-batch similarity of drugs, evaluation of generic drugs with the original drug and weighted similarity evaluation of generic drugs. The data were collected via high-performance liquid chromatography (HPLC), and then calculated by correlation coefficient, cosine, principal component analysis (PCA) and hierarchical clustering analysis (HCA). It is more suitable to use peak areas as the vector when calculating the similarity of impurity profile. After weighting the peak areas of the unspecified impurities in further evaluation of the generic quality, the generic level of different factories was differentiated and the best generic factory was picked out.
文摘The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.
文摘The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate(Compritol~?ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion-and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.
基金supported by Liaoning Institutions excellent talents support plan(No.LR2013047).
文摘The objective of this study is to investigate the feasibility of using chitosanesodium alginate(CSeSA)based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables.Using trimetazidine hydrochloride(TH)as a water-soluble model drug,influence of dissolution medium,the amount of CSeSA,the CS:SA ratio,the type of SA,the type and amount of diluents,on in vitro drug release from CSeSA based matrix tablets were studied.Drug release kinetics and release mechanisms were elucidated.In vitro release experiments were conducted in simulated gastric fluid(SGF)followed by simulated intestinal fluid(SIF).Drug release rate decreased with the increase of CSeSA amount.CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found.On the other hand,a large amount of water-soluble diluents could modify drug release profiles.It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism.In conclusion,this study demonstrated that it is possible to design extended-release tablets of watersoluble drugs using CSeSA as the matrix by optimizing formulation components,and provide better understanding about drug release from CSeSA matrix tablets.
