维生素B2片溶出度测定研究

目的 用《中国药典》方法测定249批次维生素B₂片的溶出度,同时,考察其中6个厂家样品在4种不同pH值溶出介质中的溶出曲线,并对溶出度紫外法与HPLC测定法进行比较,为全面评价药品质量提供依据。方法 采用转篮法,4种不同溶出介质各600 mL,转速为100 r/min,检测波长444 nm;HPLC测定溶出度参考《中国药典》2015年版维生素B₂原料的含量测定方法。结果 维生素B₂片总体溶出状况较好,不同厂家样品、同厂家不同批号样品均有相似的溶出行为;液相法与紫外法测定差异较大。结论 溶出度测定紫外法专属性不高,建议采用液相法测定;部分厂家产品质量不稳定,应改善生产工艺。     

伊潘立酮片溶出度一致性评价研究

目的 考察自制伊潘立酮片（1 mg规格）与参比制剂的溶出度一致性。方法 用HPLC法测定伊潘立酮在不同pH溶出介质中的溶解度,绘制伊潘立酮“pH-溶解度”曲线,测定自研制剂与参比制剂在4种不同pH溶出介质（0.1 mol/L HCl溶液、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液、水）中的溶出度,绘制溶出曲线,用相似因子法进行拟合。结果 在所选4种溶出介质下,自研制剂与参比制剂的溶出曲线相似因子f₂值均大于50。结论 自研制剂与参比制剂能够达到体外溶出一致。     

Biochemomechanics of Cerebral Vasospasm and its Resolution: II. Constitutive Relations and Model Simulations

Cerebral vasospasm is a poorly understood clinical condition that appears to result from complex biochemical and biomechanical processes that manifest as yet another example of vascular growth and remodeling. We submit that mathematical modeling holds great promise to help synthesize diverse types of data and thereby to increase our understanding of vasospasm. Toward this ultimate goal, we present constitutive relations and parametric studies that illustrate the potential utility of a new theoretical framework that combines information on wall mechanics, hemodynamics, and chemical kinetics. In particular, we show that chemical and mechanical mediators of cellular and extracellular matrix turnover can differentially dominate the progression and resolution of vasospasm. Moreover, based on our simulations, endothelial damage can significantly alter the time-course and extent of vasospasm as can impairment of autoregulation. Although the present results are consistent with salient features of clinically reported vasospasm, and thus provide some new insight, we suggest that most importantly they reveal areas of pressing need with regard to the collection of additional experimental data. Without appropriate data, our understanding of cerebral vasospasm will remain incomplete. Address correspondence to J. D. Humphrey, Department of Biomedical Engineering, Texas A&M University, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX 77843-3120, USA. Electronic mail: jhumphrey@tamu.edu

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Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release,Drug-Polymer Miscibility and Printability

The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon^® VA64, Kollicoat^® IR, Affinsiol^?15 cP, and HPMCAS either individually or as binary blends (Kollidon^® VA64 + Affinisol^? 15 cP, 1:1; Kollidon^® VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon^® VA64-Affinisol^? 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon^® VA64 and Affinisol^?15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release.     

Influence of Dissolution Media and Presence of Alcohol on the In Vitro Performance of Pharmaceutical Products Containing an Insoluble Drug

The purpose of this investigation is to determine how the dissolution media may influence the release rate of an insoluble drug in in vitro conditions. Some oral dosage forms containing ibuprofen, a molecule that shows pH-dependent solubility, are tested. They are evaluated in different media to simulate the gastrointestinal transit at paddle rotation speeds of 50 and 100 rpm. Moreover, the potential effect of different ethanol concentrations on drug release is tested. The dissolution profiles of the tablets show a similar behavior in water (pH 1.0) and phosphate buffer (pH 4.5) where the 2 doses are not completely dissolved. The soft capsules show a different behavior: a certain amount of ibuprofen, which is in solution inside the capsule, reprecipitates in water and in the pH 4.5 buffer. Instead, ibuprofen dissolves rapidly in the pH 6.8 buffer from all the formulations. In the water-ethanol solutions, the dissolution curves show a valuable increase in the drug dissolved at higher ethanol concentrations.     

Evaluation of Spironolactone Solid Dispersions Prepared by Co-Spray Drying With Soluplus® and Polyvinylpyrrolidone and Influence of Tableting on Drug Release

Solid dispersions of spironolactone with Soluplus^® and polyvinylpyrrolidone were prepared by spray drying according to a mixture experimental design and evaluated for moisture content, particle size, drug solubility, crystallinity (powder X-ray diffraction and differential scanning calorimetry), and physicochemical interactions (Fourier-transform infrared spectroscopy, Raman). In vitro dissolution was evaluated for the spray dried product itself and after compression into tablets, and prediction models were derived using multiple linear regression analysis. The spray dried products consisted of amorphous drug, indicated by the absence of crystalline powder X-ray diffraction peaks. Amorphization and interactions impacted changes in the Fourier-transform infrared spectroscopy spectra in the ranges 2900-3000 cm^?1 (C-H) and 1600-1800 cm^?1 (C=O) and caused merging at 1690 cm^?1 (C=O of lactone) and 1670 cm^?1 (C=O of thioacetyl group). In the Raman spectra, amorphization and interactions resulted in disappearance of peak at 1690 cm^?1 (C=O) and merging of peaks at 582 and 600 cm^?1 (C-S). Hydrogen bonding between the thioacetyl group of the drug with the hydroxyl groups of Soluplus^® caused marked suppression of the peak at 1190 cm^?1 (R-C(=O)-S vibration). Amorphization and interactions resulted in improved solubility and dissolution which was greatest for drug/Soluplus^® ratio 1:4 and was also demonstrated in the corresponding tablets.     

Stabilization Mechanism of Roxithromycin Tablets Under Gastric pH Conditions

Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of 3 widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A, and azithromycin. The results indicated that not only CAM but also RXM gelated under acidic conditions. Erythromycin A and azithromycin did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that 2 of the 4 macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides.