Development of hot-melt extruded drug/polymer matrices for sustained delivery of meloxicam

Chen, Yun-Chu; Moseson, Dana E.; Richard, Coralie A.; Swinney, Monica R.; Horava, Sarena D.; Oucherif, Kaoutar Abbou; Cox, Amy L.; Hawkins, Eric D.; Li, Yongzhe; DeNeve, Daniel F.; Lomeo, Joshua; Zhu, Aiden; Lyle, L. Tiffany; Munson, Eric J.; Taylor, Lynne S.; Park, Kinam; Yeo, Yoon

doi:10.1016/j.jconrel.2021.12.038

Cited by 18 publications

(7 citation statements)

References 37 publications

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“…Chen et al . have demonstrated the grayscale of each component corresponds to their densities [ 35 ]. Each voxel in the XRCT images was then classified as red, yellow, and black for hydroxychloroquine sulfate, calcium sulfate hemihydrate, and pores or background, respectively.…”

Section: Resultsmentioning

confidence: 99%

Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition

Zhang

Jiang

et al. 2022

Pharm Res

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3D printed drug delivery systems have gained tremendous attention in pharmaceutical research due to their inherent benefits over conventional systems, such as provisions for customized design and personalized dosing. The present study demonstrates a novel approach of drop-on-demand (DoD) droplet deposition to dispense drug solutions precisely on binder jetting-based 3D printed multi-compartment tablets containing 3 model anti-viral drugs (hydroxychloroquine sulfate - HCS, ritonavir and favipiravir). The printing pressure affected the printing quality whereas the printing speed and infill density significantly impacted the volume dispersed on the tablets. Additionally, the DoD parameters such as nozzle valve open time and cycle time affected both dispersing volume and the uniformity of the tablets. The solid-state characterization, including DSC, XRD, and PLM, revealed that all drugs remained in their crystalline forms. Advanced surface analysis conducted by microCT imaging as well as Artificial Intelligence (AI)/Deep Learning (DL) model validation showed a homogenous drug distribution in the printed tablets even at ultra-low doses. For a four-hour in vitro drug release study, the drug loaded in the outer layer was released over 90%, and the drug incorporated in the middle layer was released over 70%. In contrast, drug encapsulated in the core was only released about 40%, indicating that outer and middle layers were suitable for immediate release while the core could be applied for delayed release. Overall, this study demonstrates a great potential for tailoring drug release rates from a customized modular dosage form and developing personalized drug delivery systems coupling different 3D printing techniques. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11095-022-03378-9.

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Section: Resultsmentioning

confidence: 99%

Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition

Zhang

Jiang

et al. 2022

Pharm Res

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“…[40] The evolving porosity is also shown effective in enhancing drug release from a polycaprolactone matrix, practically non-degrading in the time frame of interest. [41] In the present case, Mg(OH) 2 may be replaced by Mg 3 (PO 4 ) 2 ⋅xH 2 O with a similar water solubility. Its reactivity with acidic degradants is lower than that of Mg(OH) 2 due to lower basicity, enhancing the drug release to a lesser extent than Mg(OH) 2 at the same content.…”

Section: Discussionmentioning

confidence: 88%

Long‐Acting Microparticle Formulation of Griseofulvin for Ocular Neovascularization Therapy

Chobisa,

Muniyandi,

Sishtla

et al. 2023

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Neovascular age‐related macular degeneration (nAMD) is a leading cause of vision loss in older adults. nAMD is treated with biologics targeting vascular endothelial growth factor; however, many patients do not respond to the current therapy. Here, a small molecule drug, griseofulvin (GRF), is used due to its inhibitory effect on ferrochelatase, an enzyme important for choroidal neovascularization (CNV). For local and sustained delivery to the eyes, GRF is encapsulated in microparticles based on poly(lactide‐co‐glycolide) (PLGA), a biodegradable polymer with a track record in long‐acting formulations. The GRF‐loaded PLGA microparticles (GRF MPs) are designed for intravitreal application, considering constraints in size, drug loading content, and drug release kinetics. Magnesium hydroxide is co‐encapsulated to enable sustained GRF release over >30 days in phosphate‐buffered saline with Tween 80. Incubated in cell culture medium over 30 days, the GRF MPs and the released drug show antiangiogenic effects in retinal endothelial cells. A single intravitreal injection of MPs containing 0.18 µg GRF releases the drug over 6 weeks in vivo to inhibit the progression of laser‐induced CNV in mice with no abnormality in the fundus and retina. Intravitreally administered GRF MPs prove effective in preventing CNV, providing proof‐of‐concept toward a novel, cost‐effective nAMD therapy.

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“…Hot-melt extrusion is mostly used to form solid drug solutions of poorly soluble drugs with the aim of improving their dissolution and solubility characteristics and, thus, their bioavailability after oral administration [ 45 , 46 , 47 , 48 , 49 , 50 ]. Far less studied is the application of hot-melt extrusion with the aim of sustaining the release of the API over several hours to prolong the dosing interval [ 3 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Factors That Influence Sustained Release from Hot-Melt Extrudates

Mansuroglu

Dressman

2023

Pharmaceutics

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Hot-melt extrusion is a well-established tool in the pharmaceutical industry, mostly implemented to increase the solubility of poorly soluble drugs. A less frequent application of this technique is to obtain formulations with extended release. This study investigated the influence of polymer choice, drug loading, milling and hydrodynamics on the release of a model drug, flurbiprofen, from sustained-release hot-melt extrudates with Eudragit polymers. The choice of polymer and degree of particle size reduction of the extrudate by milling were the two key influences on the release profile: the percentage release after 12 h varied from 6% (2 mm threads) to 84% (particle size <125 µm) for Eudragit RL extrudates vs. 4.5 to 62% for the corresponding Eudragit RS extrudates. By contrast, the release profile was largely independent of drug loading and robust to hydrodynamics in the dissolution vessel. Thus, hot-melt extrusion offers the ability to tailor the release of the API to the therapeutic indication through a combination of particle size and polymer choice while providing robustness over a wide range of hydrodynamic conditions.

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Development of hot-melt extruded drug/polymer matrices for sustained delivery of meloxicam

Cited by 18 publications

References 37 publications

Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition

Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition

Long‐Acting Microparticle Formulation of Griseofulvin for Ocular Neovascularization Therapy

Factors That Influence Sustained Release from Hot-Melt Extrudates

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