A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets

Bawuah, Prince; Markl, Daniel; Turner, Alice; Evans, Mike; Portieri, Alessia; Farrell, Daniel; Lucas, Ralph; Anderson, Andrew; Goodwin, Daniel; Zeitler, J. Axel

doi:10.1016/j.xphs.2020.11.041

Cited by 27 publications

(20 citation statements)

References 45 publications

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“…The correlation between the dissolution parameter T d and the porosity as measured by He pycnometry is presented in Figure 10 with second order polynomial fitting. Earlier studies have confirmed the correlation between both parameters, e.g., one study noted a decline from 96.9% API released after 45 min to 80.9% when the porosity was decreased from 67.2% to 39.9% [56,59].…”

Section: Dissolution Behaviourmentioning

confidence: 68%

“…The first step in disintegration and consequent dissolution is the penetration of liquid in the pores of the caplet. As such, porosity is one of the most important factors facilitating the process [26,55,56]. In FDM 3D-printing, the porosity of the printed object can be very high by selecting a low infill value, e.g., tablets of thermoplastic polyurethanes with 35% porosity or tablets of hydroxypropyl methylcellulose with a porosity of 80% have been produced [26,57,58].…”

Section: Porosity Analysismentioning

confidence: 99%

“…Moreover, the dissolution time does not rely solely on the porosity of the final caplet. The hydrophilicity or wetting time, for example, should also be taken into account to accurately predict the dissolution time [56].…”

Section: Dissolution Behaviourmentioning

confidence: 99%

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Influence of Print Settings on the Critical Quality Attributes of Extrusion-Based 3D-Printed Caplets: A Quality-by-Design Approach

et al. 2021

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Extrusion-based 3D-printing is an easy-to-use, cheap manufacturing technique that could be used to produce tailored precision medicines. The technique has an almost unlimited versatility since a multitude of print parameters can easily be adapted. Unfortunately, little is known of the effect of these print parameters on the critical quality attributes of the resulting printlets. In this study, practical guidelines and means to adapt certain parameters in order to achieve the desired outcome (e.g., acceptable visual quality and flexible dosing) are stipulated for medical 3D-printing using a design-of-experiments approach. The current study aims at elucidating the effect of five print parameters (infill, overlap, number of shells, layer height and layer pattern) on the mechanical properties, dimensions, weight, porosity and dissolution characteristics of a fixed-size caplet consisting of Eudragit EPO (69.3%), Polyox WSR N10 (29.7%) and zolpidem hemitartrate (1%). In terms of the mechanical properties, 3D-printed caplets possessed anisotropy where the vertical compression strength and Brinell hardness exceeded the diametral strength. In general, all 3D-printed caplets possessed acceptable mechanical strength except for a small region of the knowledge space. Dimensional analysis revealed small, statistical significant differences between different runs, although the clinical relevance of this variation is likely negligible. The weight or dose of a caplet can be varied mainly using the infill and overlap and, to a lesser extent, via the layer height and number of shells. The impact on porosity was complicated as this was influenced by many factors and their interactions. Infill was the only statistically relevant factor influencing the dissolution rate of the current formulation. This study unravels the importance of the print parameter overlap, which is a regularly neglected parameter. We also discovered that small dose variations while maintaining the same dissolution profile were possible via modifying the overlap or number of shells. However, large dose variations without affecting the dissolution behaviour could only be accomplished by size modifications of the printlet.

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Section: Dissolution Behaviourmentioning

confidence: 68%

Section: Porosity Analysismentioning

confidence: 99%

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Influence of Print Settings on the Critical Quality Attributes of Extrusion-Based 3D-Printed Caplets: A Quality-by-Design Approach

et al. 2021

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“…This similarity in dissolution profile could be linked to the porosity ( Table 5 ): Ø0.25 mm and 0.4 mm caplets possess similar porosities (59.7 and 60.9%, respectively), in contrast to a porosity of 48.6% for caplets manufactured using a Ø0.6 mm nozzle. It was shown previously that a lower porosity prolonged the disintegration time [ 61 ]. As such, porosity might provide a simple, fast screening tool for the dissolution behaviour of 3D-printed tablets.…”

Section: Resultsmentioning

confidence: 99%

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

Henry¹,

Vadder²,

Decorte³

et al. 2021

Pharmaceutics

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The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.

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“…Bawuah et al [ 62 ], on the other hand, used terahertz spectroscopy to determine tablet porosity (without the need for a model) and found a good correlation with tablet dissolution (time to 50% release), disintegration time and tablet strength and suggested it might be applicable to immediate-release products where disintegration is used to monitor drug release.…”

Section: Quality Considerations Of CM Processesmentioning

confidence: 99%

Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms

Wahlich¹

2021

Pharmaceutics

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Continuous manufacturing (CM) is defined as a process in which the input material(s) are continuously fed into and transformed, and the processed output materials are continuously removed from the system. CM can be considered as matching the FDA’s so-called ‘Desired State’ of pharmaceutical manufacturing in the twenty-first century as discussed in their 2004 publication on ‘Innovation and Continuous Improvement in Pharmaceutical Manufacturing’. Yet, focused attention on CM did not really start until 2014, and the first product manufactured by CM was only approved in 2015. This review describes some of the benefits and challenges of introducing a CM process with a particular focus on small molecule solid oral dosage forms. The review is a useful introduction for individuals wishing to learn more about CM.

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A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets

Cited by 27 publications

References 45 publications

Influence of Print Settings on the Critical Quality Attributes of Extrusion-Based 3D-Printed Caplets: A Quality-by-Design Approach

Influence of Print Settings on the Critical Quality Attributes of Extrusion-Based 3D-Printed Caplets: A Quality-by-Design Approach

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms

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