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In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.
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OBJECTIVE: To prepare mifepristone gastric retentive multi-unit pellet system (MUPs), and study its release behaviors in vitro. METHODS: A sustained release layer and mucous adhesive layer were coated onto extrusion spherized mifepristone pellets. The gastric retentive sustained release pellets were mixed with granules which were wet granulated from micronized mifepristone and compressed into MUPs tablets. Investigation and evaluation of the in vitro release of mifepristone MUPs tablets were carried out from different aspects. RESULTS: The turning point of pH value for the solubility of mifepristone was 3.0.Micronized mifepristone showed higher dissolving rate and apparent solubility. The gastric retentive mifepristone MUPs tablets had faster release than marketed mifepristone tablets. The in vitro adhesive experiment with pig stomach showed that mucous adhesive mifepristone pellets could be entrapped into the gastric mucous and retained for a long time. The accelerated stability study showed that mifepristone MUPs tablets were as stable as marketed mifepristone tablets. CONCLUSION: Novel mifepristone gastric retentive MUPs tablets are successfully prepared. The release characteristics in vitro indicate that the product may have higher bioavailability than marketed mifepristone tablets with significantly lower variability.
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OBJECTIVE: To evaluate microcrystalline cellulose(MCC) and stearic acid(SA) on extrusion-spheronisation(E-S) for aspirin sustained release pellets. METHODS: Mixtures with varying drug concentration and SA/MCC ratios were processed via non-aqueous E-S. Multi-index evaluation method were assessed by rheological behavious, drug stability and release in vitro compared with aqueous E-S. RESULTS: The extrusion was easier when SA/MCC was > 35%. When the ratio of SA/MCC was about 1, the roll effect was the best. The drug content was 65%. Compared with aqueous E-S, non-aqueous E-S was small and homogeneous pellets, better apparent characteristics, stability. There were no obvious different in drug release in vitro. CONCLUSION: These prove to be superior aids for water sensitive aspirin when exposed to non-aqueous solvent by E-S.
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Objective To prepare tamsulosin hydrochloride sustained-release pellet by coating with acrylic copolymers. Methods EUDRAGIT® NE 30 D was used as the main sustained-release material, EUDRAGIT® L 30 D-55 and Methocel® E3 were used as release adjust agent; a one layer sustained-release coating was done for tamsulosin hydrochloride-loaded pellet in bottom spray fluid bed. A three factor, three-level Box-Behnken design was used to optimize the percentages of EUDRAGIT® L 30 D-55 and Methocel® E3 in the total dry polymers and the weight gain of total dry polymers as the three nonlinear factors, which mainly influenced drug release of the pellets in the formula of sustained-release coating layer. In-vitro cumulative drug release after 2 h, 3 h and 5 h was tested and the following target range:2 h 12%-39%, 3 h 44%-70% and 5 h>70% were set for optimization. Results The formulation and process of one layer sustained-release coating, which was synergistically controlled by the three materials based on acrylic copolymers, was determined after optimization:the total dry polymers were applied with a weight gain of 12% on drug pellets, with EUDRAGIT® L 30 D-55 dry polymers and Methocel® E3 being 7% and 2% of the total dry polymers, respectively. The sustained-release pellets coated with the optimized formulation provided a release profile that was close to the predicted value and similar to that of the commercial product Harnal® capsule pellets by f2 similarity factor comparison (f2 values of three batches were 71,73 and 80). Conclusion The established formulation and process is a simple and reproducible method to prepare tamsulosin hydrochloride sustained-release pellets with good stability.
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OBJECTIVE: To design tacrolimus sustained-release pellets formula by surface degradation and erosion model, and improve the design accuracy and pertinence. METHODS: The relationship between the prescription and the surface degradation rate constant K was determined by simplex centroid design. The relationship between dissolution prediction and formulation was established and used to direct the formulation design according to the requirements of the expected dissolution. The dissolution profiles obtained by the model prediction and actual experiment were compared through hot-melt coating technology. RESULTS: The dissolution profile similarity factor f2 was over 75 between the measured and predicted dissolution profiles, and the single point error of dissolution was below 5%. CONCLUSION: Using the established model, the formula of tacrolimus sustained-release pellets can be quickly and accurately designed according to the dissolution requirement.
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OBJECTIVE: To prepare ibuprofen sustained release pellet capsules based on solid dispersion technology and evaluate the quality. METHODS: Ibuprofen matrix sustained release pellets were prepared by fluidized-bed spray drying process, using blank pill core as based pills, stearic acid as isolation layer, and PVP as carrier material. The factors influencing the pellet release were studied, including coating dispersion, preparation method, and assay method of release. RESULTS: The prepared ibuprofen sustained release pellets had ideal controlled release and characteristics, including particle size, spherical degree, drug loading, and content. CONCLUSION: A new preparation method of ibuprofen sustained release pellets with advantages of less adjuvants, no deed to micronize crude drug, simple process, and controllable quality is successfully developed. It can be used in industrialized manufacture.
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OBJECTIVE: To prepare metoprolol tartrate sustained-release pellets and investigate the relative bioavailability in Beagle dogs. METHODS: Taking aspect ratio(AR), circularity, yield, friability, fluidity as key indexes, orthogonal design was atopted to optimize the formulation, and sustained-release pellets were prepared with Surelease. RESULTS: The optimal formulation was as follows: drug loading rate 90%, adhesive 40 mL·100 g-1, spheronization rate 30 Hz, coating weight gain 12%, and aging at 60°C for 2 h. CONCLUSION: The prepared metoprolol tartrate sustained-release pellets are bioequivalent with Betaloc in Beagle dogs.
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OBJECTIVE:To investigate the technological factors that influence the drug release of nitrendipine sustained-release pellets.METHODS:The nitrendipine sustained-release pellets were prepared by extrusion-spheronization technology.By means of in vitro drug release test,the factors that influence the drug release including the amount of the wetting agent and the concentration of ethanol,extrusion speed,spheronisation speed and spheronisation time were investigated to optimize the technological conditions.RESULTS:The amount of the wetting agent and the concentration of ethanol had significant effects on drug release.The optimal concentration of ethanol was less than 35% and the optimal amount of the wetting agent was about 44 mL.Extrusion speed,spheronisation speed and spheronisation time had certain effects on drug release,and their optimal values were 48 r?min-1,1 400 r?min-1 and 5 min,respectively.CONCLUSION:The nitrendipine sustained-release pellets prepared in the above-mentioned technological conditions are up to the standard in drug release velocity.
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Object To investigate the preparation technique and optimal formulation of Breviscapin Sustained release Pellets (BSP) and the release mechanism of breviscapin from the pellets. Methods BSP was prepared by extrusion spheronization method. Based on the studies of influential factors, optimal formulation modified to release drug over 12 h was obtained by the orthogonal design. And release mechanism of breviscapin from BSP was established by equation fitting. Results Prepared BSP has such advantages as simple technique, uniformity in diameters and high loading with even contents. They can release drug for 12 h. And the release of breviscapin could be mainly controlled by diffusion associated with slight erosion. Conclusion Extrusion spheronization method is simple for the preparation of BSP, and useful for the large scale prodution.