Characterization of Controlled Release Microspheres Using FIB-SEM and Image-Based Release Prediction

Zhang, Shawn; Wu, Dan; Zhou, Liping

doi:10.1208/s12249-020-01741-w

Cited by 21 publications

(17 citation statements)

References 21 publications

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“…Furthermore, although XRM has been successfully demonstrated to differentiate amorphous API from crystalline API in certain drug systems, 40 the API domain in this project is too small to support any reliable crystallization investigation. In order to overcome this resolution limit with XRM, other 3D imaging techniques with higher resolution such as FIB-SEM 21,22,41 have been be applied in pharmaceutical drug material characterization. The resolution of FIB-SEM can be as high as ~3 nm, revealing microstructures that are not resolvable under XRM.…”

Section: Discussionmentioning

confidence: 99%

“…On a scanning electron microscopy system, a focused ion beam can be added to mill away some material and expose the cross-sectional features under the exterior surface of a sample. This system, referred to as focused ion beam scanning electron microscopy (FIB-SEM), 21,22 is employed in this project to confirm the structural features observed in XRM. The implant or powder samples were fixed on an SEM stub with carbon tape.…”

Section: Fib-sem Cross Section Imaging and Eds Elemental Studymentioning

confidence: 99%

“…21 This in turn can accelerate the design and development of robust, efficacious, and scalable LA formulations. 22 Three-dimensional (3D) image-based microstructure characterization has been successfully employed 23 in several areas such as geological samples, 24 filtration materials, 25 and energy materials. 26 In the last decade or so, 3D imaging techniques such as X-ray microscopy (XRM) have been gradually adopted for material characterization in the pharmaceutical field.…”

Section: Introductionmentioning

confidence: 99%

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Microstructure, Quality, and Release Performance Characterization of Long-Acting Polymer Implant Formulations with X-Ray Microscopy and Quantitative AI Analytics

Nagapudi¹,

Zhu

Chang³

et al. 2021

Journal of Pharmaceutical Sciences

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Long-acting implants are typically formulated using carrier(s) with specific physical and chemical properties, along with the active pharmaceutical ingredient (API), to achieve the desired daily exposure for the target duration of action. In characterizing such formulations, real-time in-vitro and in-vivo experiments that are typically used to characterize implants are lengthy, costly, and labor intensive as these implants are designed to be long acting. A novel characterization technique, combining high resolution three-dimensional X-Ray microscopy imaging, image-based quantification, and transport simulation, has been employed to provide a mechanistic understanding of formulation and process impact on the microstructures and performance of a polymer-based implant. Artificial intelligence-based image segmentation and image data analytics were used to convert morphological features visualized at high resolution into numerical microstructure models. These digital models were then used to calculate key physical parameters governing drug transport in a polymer matrix, including API uniformity, API domain size, and permeability. This powerful new tool has the potential to advance the mechanistic understanding of the interplay between drug-microstructure and performance and accelerate the therapeutic development long-acting implants.

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Section: Discussionmentioning

confidence: 99%

Section: Fib-sem Cross Section Imaging and Eds Elemental Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microstructure, Quality, and Release Performance Characterization of Long-Acting Polymer Implant Formulations with X-Ray Microscopy and Quantitative AI Analytics

Nagapudi¹,

Zhu

Chang³

et al. 2021

Journal of Pharmaceutical Sciences

Self Cite

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“…Chemical composition can be confirmed using energy dispersion X-Ray spectroscopy (EDS). FIB-SEM and EDS has been used successfully in PLGA CR microsphere depot studies 25 and polymer CR oral pellet studies. 24 In this study, an Auriga FIB-SEM (Carl Zeiss Microscopy, USA) workstation was used for FIB milling and SEM imaging of individual microsphere cross sections.…”

Section: Fib-sem and Edsmentioning

confidence: 99%

Release Mechanisms and Practical Percolation Threshold for Long-acting Biodegradable Implants: An Image to Simulation Study

Zhang

Nagapudi²,

Shen

et al. 2022

Journal of Pharmaceutical Sciences

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“…The XeF2 dry etching and the CO2 laser exposure also can fabricate such a microtoroid [32]. And then, the focused ion beam (FIB) method [33], [34] is applied to the microtoroid structure to fabricate truncated microtoroid with different height. A PNJ with an enhanced intensity of 55.21 times to the incident light, ultralong length up to 46.47 , narrow FWHM of 0.77 and high quality factor of 3308.68 generated by the semi-microtoroid.…”

Section: Introductionmentioning

confidence: 99%

Ultrahigh Quality Factor Photonic Nanojets Generated by Truncated Microtoroid Structures

et al. 2021

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A photonic nanojet (PNJ) is a highly confined light beam that focuses from the shadow side of microparticles. In 46.47 this work, we propose a PNJ with ultrahigh quality factor formed by dielectric truncated microtoroid. The key properties of PNJ, such as the maximum intensity, the length of PNJ, the full-width at half maximum (FWHM), are studied in detail using finite-difference time-domain (FDTD) analysis. The results show that a PNJ with an enhanced intensity of 55.21 times to the incident light, superlong length of 46.47 and subwavelength FWHM of 0.77 is formed by semi-microtoroid, thus, an ultrahigh quality factor of 3308.68 is achieved. More importantly, the properties of the PNJ are tunable by changing the truncated proportions of the microtoroid. The structure we proposed has the advantages of compact structure and simple experimental operation, which is expected to apply in many research fields, including optical detection, optical data storage, super-resolution image, nanopattern, nanolithography, and so on.

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Characterization of Controlled Release Microspheres Using FIB-SEM and Image-Based Release Prediction

Cited by 21 publications

References 21 publications

Microstructure, Quality, and Release Performance Characterization of Long-Acting Polymer Implant Formulations with X-Ray Microscopy and Quantitative AI Analytics

Microstructure, Quality, and Release Performance Characterization of Long-Acting Polymer Implant Formulations with X-Ray Microscopy and Quantitative AI Analytics

Release Mechanisms and Practical Percolation Threshold for Long-acting Biodegradable Implants: An Image to Simulation Study

Ultrahigh Quality Factor Photonic Nanojets Generated by Truncated Microtoroid Structures

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