Evidence map›Paper›PMID 39135353›Full record

ArticleMolecular pharmaceutics2024

In Situ Eutectic Formation in a Polymeric Matrix via Hot-Melt Reactive Extrusion and the Use of Partial Least Squares Regression Modeling for Reaction Yield Determination.

Gavin P Andrews, Alice Culkin, David S Jones, Shu Li

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Gavin P AndrewsThe Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K.ORCID 0000-0003-4551-0293
Alice CulkinThe Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K.
David S JonesThe Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K.
Shu LiThe Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K.ORCID 0000-0002-2282-3142

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There has been a significant volume of work investigating the design and synthesis of new crystalline multicomponent systems via examining complementary functional groups that can reliably interact through the formation of noncovalent bonds, such as hydrogen bonds (H-bonds). Crystalline multicomponent molecular adducts formed using this approach, such as cocrystals, salts, and eutectics, have emerged as drug product intermediates that can lead to effective drug property modifications. Recent advancement in the production for these multicomponent molecular adducts has moved from batch techniques that rely upon intensive solvent use to those that are solvent-free, continuous, and industry-ready, such as reactive extrusion. In this study, a novel eutectic system was found when processing albendazole and maleic acid at a 1:2 molar ratio and successfully prepared using mechanochemical methods including liquid-assisted grinding and hot-melt reactive extrusion. The produced eutectic was characterized to exhibit a 100 °C reduction in melting temperature and enhanced dissolution performance (>12-fold increase at 2 h point), when compared to the native drug compound. To remove handling of the eutectic as a formulation intermediate, an end-to-end continuous-manufacturing-ready process enables feeding of the raw parent reagents in their respective natural forms along with a chosen polymeric excipient, Eudragit EPO. The formation of the eutectic was confirmed to have taken place in situ in the presence of the polymer, with the reaction yield determined using a multivariate calibration model constructed by combining spectroscopic analysis with partial least-squares regression modeling. The ternary extrudates exhibited a dissolution profile similar to that of the 1:2 prepared eutectic, suggesting a physical distribution (or suspension) of the in situ synthesized eutectic contents within the polymeric matrix.

Indexed as

PolymersSolubilityChemistry, PharmaceuticalCrystallizationDrug CompoundingHot Melt Extrusion TechnologyHot TemperatureHydrogen BondingLeast-Squares AnalysisMaleatesMaleatesmaleic acidPolymersalbendazoleeutecticmechanochemistrymultivariate analysispartial least-squares regressionreactive extrusion

Identifiers

PMID39135353
PMCPMC11372829

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.