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.

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 3D 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 for 2 h were recorded 0.47, 1.55 × 10⁸ μm³, 0.44 × 10⁸ μm³ and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 10⁸ μm³, 0.38 × 10⁸ μm³ 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 3D structures to ensure better design, characterization and quality control of advanced OSDF.

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.