Evidence map›Paper›PMID 36559054›Full record

ArticlePharmaceutics2022

Thermodynamic Correlation between Liquid-Liquid Phase Separation and Crystalline Solubility of Drug-Like Molecules.

Taiga Uekusa, Tomohiro Watanabe, Daiju Watanabe, Kiyohiko Sugano

Abstract read
In one paragraph

Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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.

Taiga UekusaMolecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higasi, Kusatsu 525-8577, Shiga, Japan.
Tomohiro WatanabeMolecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higasi, Kusatsu 525-8577, Shiga, Japan.
Daiju WatanabeMolecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higasi, Kusatsu 525-8577, Shiga, Japan.
Kiyohiko SuganoMolecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higasi, Kusatsu 525-8577, Shiga, Japan.ORCID 0000-0001-5652-1786

Funding

Japan Science and Technology Agency JPMJFS2146
6 · The paper itself

Abstract

The purpose of the present study was to experimentally confirm the thermodynamic correlation between the intrinsic liquid−liquid phase separation (LLPS) concentration (S0LLPS) and crystalline solubility (S0c) of drug-like molecules. Based on the thermodynamic principles, the crystalline solubility LLPS concentration melting point (Tm) equation (CLME) was derived (log10S0C=log10S0LLPS−0.0095Tm−310 for 310 K). The S0LLPS values of 31 drugs were newly measured by simple bulk phase pH-shift or solvent-shift precipitation tests coupled with laser-assisted visual turbidity detection. To ensure the precipitant was not made crystalline at <10 s, the precipitation tests were also performed under the polarized light microscope. The calculated and observed log10S0C values showed a good correlation (root mean squared error: 0.40 log unit, absolute average error: 0.32 log unit).

Indexed as

drug-likeintrinsic solubilityliquid–liquid phase separationmelting point

Identifiers

PMID36559054
PMCPMC9782016

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Registered trials

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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.