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Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.
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The poor solubility of cyclosporine A (CsA) in water limits its oral absorption. We prepared CsA/ Soluplus/SDS complex, which can form CsA/Soluplus/SDS supersaturated micelles (CSS-SM) after hydration. Then, We further prepared CSS-SM osmotic pump tablets (CSS-SM-T). CSS-SM had a particle size of 156 nm, where in encapsulation efficiency and drug loading efficiency of CsA were 89.0% and 17.5%, respectively. CSS-SM-T achieved zero-level drug release in vitro. Pharmacokinetic data from Beagle dogs (all animal experiments were conducted under the guidelines approved by the Institutional Animal Care and Use Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences) indicated that CsA in the ordinary osmotic pump tablets was hardly absorbed after orally administered; despite slightly lower bioavailability [relative bioavailability: (85.1 ± 47.4) %] than that of Sandimmum Neoral, CSS-SM-T displayed lower fluctuations in CsA plasma concentration and obvious sustained-release characteristics in vivo, implying lower toxicity. Therefore, CSS-SM-T provides a new research idea for the design and development of oral sustained- and controlled-release preparations of poorly water-soluble drugs.
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OBJECTIVE: To optimize the formulation of ambroxol hydrochloride sandwich osmotic pump tablets using Box-Behnken design response surface method. METHODS: Firstly, significant factors, including amount of glucose, ratio of pore former to weight of coating, and thicknesss of coating, were chosen carefully by single-factor methods, then Box-Behnken design-response surface method was adopted to understand the effects of these factors on the drug release by using similarity factor f2 as evaluation index. And multiple linear regression model and quadratic polynomial equation were established to evaluate the relationship between these factors and similarity factor f2. Secondly, the permeation mechanism of sandwich osmotic pump was studied carefully by SEM and drug release behavior investigation. RESULTS: The quadratic polynomial equation was ideal to fit the prediction result of drug release; the optimal formulation according to Design-Expert8.0.5 software was established as follows: 50 mg of glucose, 8% of pore former, 9% of coating weight. The f2 was approximate 89.33 compared with ideal drug release curve, which was relatively close to the model-predicted f2 value (88.89). Through investigation of permeation mechanism, it was found that the drug release from this delivery system was driven by osmotic pressure difference between the interior of tablets and the release medium. By means of SEM observation, it was shown that some pores on the coating surface were produced after drug release in the medium, but few before drug release, which cued that a lot of medium got into the interior of tablets through the tunnels formed by the porogen in the coating. CONCLUSION: Box-Behnken design method can be used to optimize the formulation of sandwich osmotic pump tablets.
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Objective To use the inclusion technology for improving the solubility and dissolution rate of baicalein from monolithic osmotic pump tablet containing inclusion complex of baicalein by observing the effects of the core and coating on in vitro drug release. Methods Baicalein-inclusion complex was prepared by the inclusion technique, and its solubility and dissolution rate were determined. The percent of cumulative release was used to evaluate the drug release profile in vitro. Single factor analysis was used to study the effects of NaCl and PEO amounts, coating weight and plasticizer amount on drug release. Then orthogonal design was used to select the optimal formulation of monolithic osmotic pump tablet containing baicalein-inclusion complex. Results The solubility and dissolution rate of baicalein were greatly enhanced when prepared into inclusion complex. Orthogonal design results indicated that PEO content in the tablet core and plasticizer PEG 400 in the coating had significant effects on the drug release, and the optimum formulation was: baicalein-inclusion complex 180 mg, NaCl 100 mg, PEO 80 mg, coating weight 4% and plasticizer 9%. The tablets with optimized formula achieved the desired zero-order release profile (r=0.997 8) within 12 hours and the cumulative release was higher than 88%. Conclusion Monolithic osmotic pump tablet of baicalein has been successfully prepared using inclusion complex as the intermediate, and the release behavior accords with zero-order kinetics equation.
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OBJECTIVE: To optimize the formulation of Yuanhu Zhitong push-pull osmotic pump tablets by Box-Behnken design-response surface method.
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Objective To prepare gensenosides microbore osmotic pump tablet, and to investigate releasing in vitro. Methods We prepared gensenosides microbore osmotic pump tablet to investigate the release in vitro by cumulative release rate in different time. Results We prepared gensenosides microbore osmotic pump tablet successfully and investigated releasing in vitro and drew the release curve. Conclusion The release of gensenosides microbore osmotic pump tablet in vitro consists with zero order release rule. It can chalk the effect in ten hours.
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OBJECTIVE:To prepare urapidil osmotic pump tablet(OPT) characterized by 24 h constant drug release in vitro.METHODS:OPT of urapidil was prepared using NaCl and low or high moleculan weight PEO(Mr 4?106、2?105) as core,CA and PEG-400 as the coating material.Similarity factor was used to evaluate formulation of osmotic pump tablets.The drug release mechanism was investigated as well.RESULTS:The optimal core formulation consisted of urapidil 60 mg,NaCl 190 mg,PEO(Mr 4?106) 90 mg,PEO(Mr 2?105) 90 mg.The drug was released from OPT at controlled rate 24 h.CONCLUSION:The preparation of osmotic pump tablets was simple and characterized by zero-order release.
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AIM:To optimize total flavone of herba epimediumon microporosity osmotic pump tablets by boxbehnken design-response surface methodology. METHODS:Osmotic agent (lactose),dosage of plastificator (dibutyl phthalate),and coating weight gain were selected as key factors of influencing total flavone delivery. Total flavones cumulatiive yield in 12 h and fitting approximation was regarded as the response. Design Expert method useful for the modeling and analysis was to optimize the response. RESULTS:Response surface surface obtained repre-sented maximum one which conformed to the zero-order delivery rate equation. CONCLUSION:Optimal excipient formulation of total epimedium flavone microporosity osmotic pump tablet consists of 0. 18 g of lactose,0. 26 ratio of dibutyl phthalate to acetyl celulose and 7. 7% of coating weight gain.