Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism.

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.

Polysaccharides from Armillariella tabescens mycelia ameliorate insulin resistance in type 2 diabetic mice.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia mainly due to insulin resistance. The objective of this study was to investigate the effects of polysaccharides from Armillariella tabescens mycelia (AT) on insulin resistance in mice fed a high-fat diet in combination with streptozotocin to induce T2DM. Following treatment with different doses of AT, hyperglycemia and lipid metabolism dysfunction, insulin resistance, and hepatic function-related indices were markedly ameliorated; the histopathological alterations, oxidative stress, and inflammatory reaction in hepatic tissue were also alleviated; most importantly, AT inhibited the expression of hepatic thioredoxin-interacting protein (TXNIP) to repress the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and activated the 5'AMP-activated protein kinase (AMPK) pathway in a dose-dependent manner in T2DM mice. In conclusion, these findings revealed that the hypoglycemic and hypolipidemic activities of AT were associated with the alleviation of insulin resistance through repression of the TXNIP/NLRP3 inflammasome pathway and activation of the AMPK pathway.

Polysaccharides from Armillariella tabescens mycelia ameliorate renal damage in type 2 diabetic mice.

Diabetic kidney disease (DKD), accompanied by chronic low-grade inflammation, is one of the most common complications of diabetes. Armillariella tabescens has potent anti-inflammatory and immunomodulatory properties. The purpose of the present study was to investigate the effects of polysaccharides from Armillariella tabescens mycelia (AT) on the kidney in type 2 diabetic mice and explore the underlying mechanism. The mice were randomized into 4 groups: normal control (NC), diabetic control (DC), DC + 200 mg/kg AT (LAT), and DC + 400 mg/kg AT (HAT). The results showed that compared with the NC group, the levels of fasting blood glucose, renal function-related indices, and serum pro-inflammatory mediators including lipopolysaccharide (LPS), interleukin (IL)-1ß, and IL-18 were elevated; the renal morphopathological alterations, oxidative stress, and nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome-mediated inflammation and renal fibrosis were aggravated; the intestinal microbiota dysbiosis and colonic inflammation and barrier dysfunction were deteriorated in the DC group. After supplementation with AT, the aforementioned indices were ameliorated in the AT treatment groups, especially in the HAT group. In conclusion, these results demonstrated that modulating the intestinal microbiota and inflammatory reaction was implicated in the effects of AT against DKD in mice.

Fractal structure determines controlled release kinetics of monolithic osmotic pump tablets.

OBJECTIVES: To calculate the fractal dimension values of felodipine osmotic pump tablets during drug dissolution and to characterize the mechanism of the controlled drug release kinetics through three-dimensional fractal data. METHODS: Three-dimensional fractal values of volume (Df,volume ) and surface (Df,surface ) of the tablet core were calculated based on the box counting method. KEY FINDINGS: During the process of release of felodipine, both Df,volume and Df,surface were within the range of 2-3 and then changed markedly after a period of 3.0 h release, corresponding to extensive changes in entire shape, interior porous channels and surface structure of the tablet core. The curve of Df,volume mirrored that for tablet volume, however the curve of Df,surface was quite different from that of the surface area. Results showed that values of Df,surface correlated well with the drug release rate. Df,surface was found to be an efficient fractal parameter that could be used to characterize the complex changes to the tablet core that take place during drug release. CONCLUSIONS: The fractal dimension can be used as a quantitative indicator reflecting the drug release performance and be regarded as a key indicator for the quality control of oral controlled drug delivery systems.

Microstructural investigation to the controlled release kinetics of monolith osmotic pump tablets via synchrotron radiation X-ray microtomography.

Tomographic imaging techniques are attractive tools for the visualization of the internal structural characteristics of pharmaceutical solid dosage forms. In this paper, the internal structure of the tablet core for a monolith osmotic drug delivery system, felodipine sustained-release tablet, was visualized via synchrotron radiation X-ray computed microtomography during the drug release process. The surface areas and three dimensional parameters of the tablet core were calculated based on the three dimensional reconstruction of the images. At different stages of the drug release process, the surface morphology, the hydration, the swelling, and the structure changing of the tablet, were visualized from the two dimensional monochrome X-ray images. The three dimensional volumes of the remaining tablet core correlated well with the percentages of felodipine (R=0.9988). Also, the three dimensional surface area almost unchanged during the drug release process, which clearly demonstrated the intrinsic drug release mechanism of the osmotic drug delivery system. In conclusion, the synchrotron radiation X-ray computed microtomography, with rapid acquisition, high intensity and micro-scale spatial resolution, was found to be a useful tool for the quantitative elucidation of the intrinsic drug release kinetics and the three dimensional parameters such as surface areas of the remained core obtained by the synchrotron radiation. Thus, X-ray computed microtomography can be considered as a new and complimentary analytical tool to standard compendial pharmaceutical tests for quality control of osmotic drug delivery systems.