A comprehensive overview of extended release oral dosage forms manufactured through hot melt extrusion and its combination with 3D printing

Nashed, Nour; Lam, Matthew; Nokhodchi, Ali

doi:10.1016/j.ijpharm.2021.120237

Cited by 32 publications

(21 citation statements)

References 101 publications

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“…It is unclear whether porosity has influenced the dispersion and subsequent release of the SMEDDS from PLA formulations; however, it is believed to have a negligible effect considering the rapid dispersion time and hydrophobicity of PLA. This demonstrates the need for more research into miscible 3DP PLA-SMEDDS core shell designs, and to optimising the printing resolution to eliminate porosity, that may be achievable with PLH-type filament and continuous printing methods [42].…”

Section: Discussionmentioning

confidence: 99%

A 3D-Printed Polymer–Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations

Barber

Dumont²,

Caisse³

et al. 2021

Pharmaceutics

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3D printing is a rapidly growing area of interest within pharmaceutical science thanks to its versatility in creating different dose form geometries and drug doses to enable the personalisation of medicines. Research in this area has been dominated by polymer-based materials; however, for poorly water-soluble lipophilic drugs, lipid formulations present advantages in improving bioavailability. This study progresses the area of 3D-printed solid lipid formulations by providing a 3D-printed dissolvable polymer scaffold to compartmentalise solid lipid formulations within a single dosage form. This allows the versatility of different drugs in different lipid formulations, loaded into different compartments to generate wide versatility in drug release, and specific control over release geometry to tune release rates. Application to a range of drug molecules was demonstrated by incorporating the model lipophilic drugs; halofantrine, lumefantrine and clofazimine into the multicompartmental scaffolded tablets. Fenofibrate was used as the model drug in the single compartment scaffolded tablets for comparison with previous studies. The formulation-laden scaffolds were characterised using X-ray CT and dispersion of the formulation was studied using nephelometry, while release of a range of poorly water-soluble drugs into different gastrointestinal media was studied using HPLC. The studies show that dispersion and drug release are predictably dependent on the exposed surface area-to-volume ratio (SA:V) and independent of the drug. At the extremes of SA:V studied here, within 20 min of dissolution time, formulations with an SA:V of 0.8 had dispersed to between 90 and 110%, and completely released the drug, where as an SA:V of 0 yielded 0% dispersion and drug release. Therefore, this study presents opportunities to develop new dose forms with advantages in a polypharmacy context.

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Section: Discussionmentioning

confidence: 99%

A 3D-Printed Polymer–Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations

Barber

Dumont²,

Caisse³

et al. 2021

Pharmaceutics

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“…Fused deposition modeling (FDM) is one of the 3D printing techniques used to fabricate solid dosage forms. FDM has gained great interest as it can contribute to the potential future of personalized medicine and digital pharmacy [ 1 ]. The filaments for FDM can be prepared by hot-melt extrusion (HME) with a suitable diameter to ensure compatibility with the printing nozzle.…”

Section: Introductionmentioning

confidence: 99%

“…High temperatures are applied in both technologies (FDM and HME), though it is higher in FDM than in HME, causing great concern for the stability of dosage forms. Thus, the techniques are only suitable for thermostable excipients and active pharmaceutical ingredients (APIs) [ 1 ]. Solid dispersion formulations are the most common type of formulations made by HME and FDM where thermoplastic polymers are usually used for this purpose.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, determination of the melting point, glass transition, and thermal stability are some of the important pre-formulation tests. In addition, mechanical characteristics should be investigated before selecting formulations to be printed [ 1 ]. Filaments to be used in FDM need to have adequate elasticity to withstand coiling around spools and extrusion while printing without rupture or deformation.…”

Section: Introductionmentioning

confidence: 99%

“…Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC) were found to be compatible blends [ 3 ] and have been used in several studies [ 4 , 5 ]. Both polymers are thermostable and compatible with HME and FDM [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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An Insight into the Impact of Thermal Process on Dissolution Profile and Physical Characteristics of Theophylline Tablets Made through 3D Printing Compared to Conventional Methods

et al. 2022

Self Cite

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The dissolution profile is of great importance in drug delivery and is affected by the manufacturing method. Thus, it is important to study the influence of the thermal process on drug release in emerging technologies such as 3D printing-fused deposition modeling (FDM). For this purpose, the characteristics of 3D printed tablets were compared to those of tablets prepared by other thermal methods such as hot-melt extrusion (HME) and non-thermal methods such as physical mixture (PM). Theophylline was used as a drug model and blends of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) were used as a matrix former. The solid state of the drug in all formulations was investigated by differential scanning calorimetry, X-ray powder diffraction, and Fourier-transformed infrared spectroscopy. All studied tablets had the same weight and surface area/volume (SA/V). Dissolution data showed that, for some formulations, printed tablets interestingly had a faster release profile despite having the highest hardness values (>550 N) compared to HME and PM tablets. Porosity investigations showed that 100% infill printed tablets had the highest porosity (~20%) compared to HME (<10%) and PM tablets (≤11%). True density records were the lowest in printed tablets (~1.22 g/m3) compared to tablets made from both HME and PM methods (~1.26 g/m3), reflecting the possible increase in polymer specific volume while printing. This increase in the volume of polymer network may accelerate water and drug diffusion from/within the matrix. Thus, it is a misconception that the 3D printing process will always retard drug release based on increased tablet hardness. Hardness, porosity, density, solid-state of the drug, SA/V, weight, and formulation components are all factors contributing to the release profile where the total balance can either slow down or accelerate the release profile.

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Development and Bioequivalence of 3D‐Printed Medication at the Point‐of‐Care: Bridging the Gap Toward Personalized Medicine

Lyousoufi

Lafeber

Kweekel

et al. 2023

Clin Pharma and Therapeutics

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Personalized medicine is currently hampered by the lack of flexible drug formulations. Especially for pediatric patients, manual compounding of personalized drug formulations by pharmacists is required. Three‐Dimensional (3D) printing of medicines, which enables small‐scale manufacturing at the point‐of‐care, can fulfill this unmet clinical need. This study investigates the feasibility of developing a 3D‐printed tablet formulation at the point‐of‐care which complies to quality requirements for clinical practice, including bioequivalence. Development, manufacturing, and quality control of the 3D‐printed tablets was performed at the manufacturing facility and laboratory of the department of Clinical Pharmacy and Toxicology at Leiden University Medical Center. Sildenafil was used as a model drug for the tablet formulation. Along with the 3D‐printed tablets a randomized, an open‐label, 2‐period, crossover, single‐dose clinical trial to assess bioequivalence was performed in healthy adults. Bioequivalence was established if areas under the plasma concentration curve from administration to the time of the last quantifiable concentration (AUC0‐t) and maximum plasma concentration (Cmax) ratios were within the limits of 80.00–125.00%. The manufacturing process provided reproducible 3D‐printed tablets that adhered to quality control requirements and were consequently used in the clinical trial. The clinical trial was conducted in 12 healthy volunteers. The 90% confidence intervals (CIs) of both AUC0‐t and Cmax ratios were within bioequivalence limits (AUC0‐t 90% CI: 87.28–104.14; Cmax 90% CI: 80.23–109.58). For the first time, we demonstrate the development of a 3D‐printed tablet formulation at the point‐of‐care that is bioequivalent to its marketed originator. The 3D printing of personalized formulations is a disruptive technology for compounding, bridging the gap toward personalized medicine.

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A comprehensive overview of extended release oral dosage forms manufactured through hot melt extrusion and its combination with 3D printing

Cited by 32 publications

References 101 publications

A 3D-Printed Polymer–Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations

A 3D-Printed Polymer–Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations

An Insight into the Impact of Thermal Process on Dissolution Profile and Physical Characteristics of Theophylline Tablets Made through 3D Printing Compared to Conventional Methods

Development and Bioequivalence of 3D‐Printed Medication at the Point‐of‐Care: Bridging the Gap Toward Personalized Medicine

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