Optimization of taste-masking on ibuprofen microspheres with selected structure features

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography(SR-μCT) to establish the relationship between the preparation process and microsphere architectures. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects.

Three dimensional distribution of surfactant in microspheres revealed by synchrotron radiation X-ray microcomputed tomography

This study investigated the formulation mechanism of microspheres via internal surfactant distribution. Eudragit L100 based microspheres loaded with bovine serum albumin were prepared by solid in oil in oil emulsion solvent evaporation method using acetone and liquid paraffin system containing sucrose stearate as a surfactant. The fabricated microspheres were evaluated for encapsulation efficiency, particle size, production yield, and in vitro release characteristics. The internal structures of microspheres were characterized using synchrotron radiation X-ray microcomputed tomography(SR-μCT). The enhanced contrast made the sucrose stearate distinguished from Eudragit to have its three dimensional(3D) distribution. Results indicated that the content and concentration determined the state of sucrose stearate and had significant influences on the release kinetics of protein. The dispersity of sucrose stearate was the primary factor that controlled the structure of the microspheres and further affected the encapsulation efficiency, effective drug loading, as well as in vitro release behavior. In conclusion, the 3D internal distribution of surfactant in microspheres and its effects on protein release behaviors have been revealed for the first time. The highly resolved 3D architecture provides new evidence for the deep understanding of the microsphere formation mechanism.

Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.

Structural and functional imaging of brains

Analyzing the complex structures and functions of brain is the key issue to understanding the physiological and pathological processes.Although neuronal morphology and local distribution of neurons/blood vessels in the brain have been known,the subcellular structures of cells remain challenging,especially in the live brain.In addition,the complicated brain functions involve numerous functional molecules,but the concentrations,distributions and interactions of these molecules in the brain are still poorly understood.In this review,frontier techniques available for multiscale structure imaging from organelles to the whole brain are first overviewed,including magnetic resonance imaging(MRI),computed tomography(CT),positron emission tomography(PET),serial-section electron microscopy(ss EM),light microscopy(LM)and synchrotron-based X-ray microscopy(XRM).Specially,XRM for three-dimensional(3D)imaging of large-scale brain tissue with high resolution and fast imaging speed is highlighted.Additionally,the development of elegant methods for acquisition of brain functions from electrical/chemical signals in the brain is outlined.In particular,the new electrophysiology technologies for neural recordings at the single-neuron level and in the brain are also summarized.We also focus on the construction of electrochemical probes based on dual-recognition strategy and surface/interface chemistry for determination of chemical species in the brain with high selectivity and long-term stability,as well as electrochemophysiological microarray for simultaneously recording of electrochemical and electrophysiological signals in the brain.Moreover,the recent development of brain MRI probes with high contrast-to-noise ratio(CNR)and sensitivity based on hyperpolarized techniques and multi-nuclear chemistry is introduced.Furthermore,multiple optical probes and instruments,especially the optophysiological Raman probes and fiber Raman photometry,for imaging and biosensing in live brain are emphasized.Finally,a brief perspective on existing challenges and further research development is provided.

Synchrotron radiation-based Fourier-transform infrared spectromicroscopy for characterization of the protein/peptide distribution in single microspheres

The present study establishes a visualization method for the measurement of the distribution and localization of protein/peptide constituents within a single poly-lactide-co-glycolide(PLGA) microsphere using synchrotron radiation–based Fourier-transform infrared spectromicroscopy(SR-FTIR).The representative infrared wavenumbers specific for protein/peptide(Exenatide) and excipient(PLGA) were identified and chemical maps at the single microsphere level were generated by measuring and plotting the intensity of these specific bands.For quantitative analysis of the distribution within microspheres,Matlab software was used to transform the map file into a 3D matrix and the matrix values specific for the drug and excipient were extracted.Comparison of the normalized SR-FTIR maps of PLGA and Exenatide indicated that PLGA was uniformly distributed,while Exenatide was relatively non-uniformly distributed in the microspheres.In conclusion,SR-FTIR is a rapid,nondestructive and sensitive detection technology to provide the distribution of chemical constituents and functional groups in microparticles and microspheres.

Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats

Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.

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

Defining and visualizing the three-dimensional(3 D) 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 3 D 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 3 D 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 3 D 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 observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.

Simultaneous 3D Visualization of the Microvascular and Neural Network in Mouse Spinal Cord Using Synchrotron Radiation Micro-Computed Tomography

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases.However,ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking.In this study,we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography(SRμCT)to visualize the 3D neurovascular network in the mouse spinal cord.Using our method,the 3D neurons,nerve fibers,and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning.Besides,we found that the 3D morphology of neurons,nerve fiber tracts,and vasculature visualized by SRjiCT were highly consistent with that visualized using the histological method.Moreover,the 3D neurovascular structure could be quantitatively evaluated by the combined methodology.The method shown here will be useful in fundamental neuroscience studies.