Multi-scale and multi-dimensional structures in dosage forms and drug delivery system innovation

来源 :第二届全国生物颗粒学术研讨会、第三届国际工业药学和临床药学研讨会暨第一届岭南国际药学大会 | 被引量 : 0次 | 上传用户:asjkdhfjkhasdjklfhjk
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  In combination with image processing and 3D reconstruction, the Synchrotron Radiation Micro-Computed Tomography (SR-μ CT) has demonstrated that SR-μ CT based three dimensional structure analysis opens up a new understanding of the fine structures and their interactions among drug delivery systems (DDS).From macro to mesoscale, we have jointly defined four levels of the structures of pharmaceutics from dosage forms to molecules, namely:1) Dosage forms with macro-structures in large size easily being observed by nude eyes as tablets,capsules, pellets;2) Particulate dosage forms as microspheres, or intermediates to prepare large dosage forms, e.g.,granules for the preparation of powders, capsules and tablets.The structures of the crystals of either drugs or non-active materials also play a key role to the dosage forms.3) Dynamic structures for dosage forms when they are functioning with drug release in liquid media, e.g., hydration, gelling, erosion, swelling.4) Molecular or meso-scope structures of drugs and the molecular assemblies as polymorphs of drugs, or nano-drug delivery systems as micelles, nanoparticles, liposomes, etc.The multi-scale structures in dosage forms and drug delivery system are typically overlapping macro-, micro-to meso-scale levels.Theres no single conventional device or instrument to cover a scale from nanometer to millimeters.With wide X-ray energy, its high intensity, high brilliance and high polarization, SR-μ CT has been proved a powerful tool in multi-scale structure determination from dozens nanometer to centimeters, which covers the scale of most nano-systems to granules, to dosage forms in large sizes like tablets.After a computed tomography, the reconstructed architectures of particles or dosage forms are measured quantitatively for structural characteristics, which help to correlate the release kinetics with the three dimensional (3D) characteristics of dosage forms.The multi-dimensional structures in dosage forms and drug delivery system are essentially of importance, since none of the dosage forms is in the shape or structure of integral dimensions.The irregular structure in the core of a tablet during release phase and the complex internal architectures inside particulate systems like microspheres all need novel advanced methodology and instrument.Based upon structure reconstruction by SR-μ CT, the non-integral Fractal dimension is one answer to the multi-dimension challenges.The microstructures undergo dynamic changing when the dosage form/particulate systems are functioning.A dynamic SR-μ CT captures internal structure changing with time at high resolution, offering new ways to investigate the dynamical micro-structures inside a macro-structure of the dosage forms.
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