Fractal structure determines controlled release kinetics of monolithic osmotic pump tablets

Yin, Xianzhen; Li, Haiyan; Liu, Ruihao; Chen, Jing; Ji, J.; Shao, Qun; Xiao, Tiqiao; York, Peter; He, Yeping; Zhang, Jiwen

doi:10.1111/jphp.12056

Cited by 21 publications

(7 citation statements)

References 20 publications

(45 reference statements)

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“…This indicates increased complexity and tortuosity of tolfenamic acid and bupivacaine clusters in the UHMWPE matrix. Previously we demonstrated that the initial release is primarily driven by the “small” drug clusters, 16 and increased fractal dimension is often associated with increased drug diffusion from the polymeric matrix 44,45 . We attribute the pronounced increase in the tolfenamic elution to the increased complexity and tortuosity of “small” drug clusters.…”

Section: Discussionmentioning

confidence: 72%

“…Previously we demonstrated that the initial release is primarily driven by the "small" drug clusters, 16 and increased fractal dimension is often associated with increased drug diffusion from the polymeric matrix. 44,45 We attribute the pronounced increase in the tolfenamic elution to the increased complexity and tortuosity of "small" drug clusters. Due to its relatively low MIC, even a small change in tolfenamic acid elution can explain a substantial increase in the antibacterial activity of the dual-drug loaded UHMWPE.…”

Section: Discussionmentioning

confidence: 91%

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Dual‐analgesic loadedUHMWPEexhibits synergistic antibacterial effects againstStaphylococci

et al. 2022

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Total joint arthroplasty is one of the most common surgeries in the United States, with almost a million procedures performed annually. Periprosthetic joint infections (PJI) remain the most devastating complications associated with total joint replacement. Effective antibacterial prophylaxis after primary arthroplasty could substantially reduce incidence rate of PJI. In the present study we propose to provide post‐arthroplasty prophylaxis via dual‐analgesic loaded ultra‐high molecular weight polyethylene (UHMWPE). Our approach is based on previous studies that showed pronounced antibacterial activity of analgesic‐ and NSAID‐loaded UHMWPE against Staphylococci. Here, we prepared bupivacaine/tolfenamic acid‐loaded UHMWPE and assessed its antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Dual‐drug loaded UHMWPE yielded an additional 1–2 log reduction of bacteria, when compared with single‐drug loaded UHMWPE. Analysis of the drug elution kinetics suggested that the observed increase in antibacterial activity is due to the increased tolfenamic acid elution from dual‐drug loaded UHMWPE. We showed that the increased fractal dimension of the drug domains in UHMWPE could be associated with increased drug elution, leading to higher antibacterial activity. Dual‐analgesic loaded UHMWPE proposed here can be used as part of multi‐modal antibacterial prophylaxis and promises substantial reduction in post‐arthroplasty mortality and morbidity.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 91%

Dual‐analgesic loadedUHMWPEexhibits synergistic antibacterial effects againstStaphylococci

et al. 2022

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“…Here we define "morphological quantification" as a type of numerical method that calculates certain morphological parameters from the reconstructed 3D tomography data, for quantifying certain aspects of the sample structure. These morphological parameters include, but are not limited to, phase volume fraction (including porosity) [99]- [102], surface area [100], [102]- [105], particle size distribution [106], phase connectivity [100], [104], [105], triple phase boundaries (TPB) [101], [107], tortuosity [100], [105], [108], pore throat size distributions [109], phase complexity [110], [111], channel diameter distribution [112], minimum representative volume [109], [113], fractal dimensions [102]. A selected case study, which highlights the applications of morphological quantification in the investigation of solid oxide fuel cells (SOFCs) using X-ray tomography, is discussed below.…”

Section: Morphological Quantificationmentioning

confidence: 99%

To get the most out of high resolution X-ray tomography: A review of the post-reconstruction analysis

Liu

Kiss

Larsson

et al. 2016

Spectrochimica Acta Part B: Atomic Spectroscopy

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X-ray microscopy has been well-recognized as one of the most important techniques for research in a wide range of scientific disciplines including materials science, geoscience, and bio-medical science. Advances in X-ray sources, optics, detectors, and imaging methodologies have made significant improvements to non-destructive reconstructions of the three dimensional (3D) structure of specimens over a wide range of length scales with different contrast mechanisms. A strength of 3D imaging is a "seeing is believing" way of reporting and analyzing data to better understand the structure/function characteristics of a sample. In addition to the excellent visualization capability, X-ray computed tomography has a lot more to offer. In this article, we review some of the experimental and analytical methods that enrich and extract scientifically relevant information from tomographic data. Several scientific cases are discussed along with how they enhance the tomographic dataset.

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“…Due to the availability of the synchrotron radiation light source SR-μCT permits the rapid acquisition of data with high intensity illumination and micro-scale spatial resolution through a high specification detector (20). This technique has been well documented while investigating the morphology and internal structures of granules and solid dosing forms (21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Release Behaviour of Single Pellets and Internal Fine 3D Structural Features Co-define the In Vitro Drug Release Profile

Yang

Yin

Wang

et al. 2014

AAPS J

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Multi-pellet formulations are advantageous for the controlled release of drugs over single-unit dosage forms. To understand the diffusion controlled drug release mechanism, the pellet structure and drug release from a single pellet (not at dose level) were studied using synchrotron radiation X-ray computed microtomography (SR-μCT) and a sensitive LC/MS/MS method. The purpose of this article is to introduce a powerful, non-invasive and quantitative technique for studying individual pellet microstructures and to investigate the relationship between the microstructure and drug release from single pellets. The data from the single pellet dissolution measurements demonstrated that the release profile of capsules containing approximately 1,000 pellets per unit dose was the summation of the release profiles of the individual pellets. The release profiles of single tamsulosin hydrochloride (TSH) pellets formed three groups when a cluster analysis was performed, and the dissolution rate of the individual pellets correlated well with the combined effects of the drug loading, volume and surface area of the pellets (R(2) = 0.9429). In addition, the void microstructures within the pellet were critical during drug release. Therefore, SR-μCT is a powerful tool for quantitatively elucidating the three-dimensional microstructure of the individual pellets; because the microstructure controls drug release, it is an important parameter in the quality control of multi-pellet formulations.

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Fractal structure determines controlled release kinetics of monolithic osmotic pump tablets

Abstract: 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.

Cited by 21 publications

References 20 publications

Dual‐analgesic loadedUHMWPEexhibits synergistic antibacterial effects againstStaphylococci

Dual‐analgesic loadedUHMWPEexhibits synergistic antibacterial effects againstStaphylococci

To get the most out of high resolution X-ray tomography: A review of the post-reconstruction analysis

Release Behaviour of Single Pellets and Internal Fine 3D Structural Features Co-define the In Vitro Drug Release Profile

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