Designing Safer Solvents to Replace Methylene Chloride for Liquid Chromatography Applications Using Thin-Layer Chromatography as a Screening Tool

Round 1

Reviewer 1 Report

The submitted manuscript describes and discusses the results of an original research project carried out to dissolution testing along with applying the Hansen Solubility Parameter theory. Obtain results provide guidance for identifying and evaluating safer solvents to separate active pharmaceutical ingredients with the use of chromatography. Also described and discussed is the successful application of the analytical procedure. The manuscript describes and discusses logically designed experiments and presents results that are expected to be of large interest for the scientific community. It is an interesting study with a novel approach. The paper in the whole is well designed and results sound. Nevertheless, the manuscript needs a minor revision:

* Fig. 2 - should be better described in the text,

* Fig. 4-7 - should be better of quality, without internal axixes.

Author Response

To MDPI Separations Reviewers,

Thank you for your letter regarding our manuscript “Designing Safer Solvents to Replace Methylene Chloride for Liquid Chromatography Applications Using Thin Layer Chromatography as a Screening Tool” (MDPI Separations). We are grateful for the constructive feedback you have provided. We have carefully reviewed your feedback and have made changes to the manuscript item by item to address all your comments.  Please find the proposed corrections attached.

Author Response File: Author Response.pdf

Reviewer 2 Report

In my opinion, the work presented in this manuscript is incomplete. More work is needed. More explanations are necessary.  My considerations are:

Please add in the title Thin-layer chromatography

Binary mixtures containing acetaminophen and caffeine should be better justified. What about aspirin and ibuprofen?.

The spheres for aspirin and ibuprofen should be included in supporting information

Fig 5-7. Please explain how and to whom R_f is owed

Conclusions section:

“Performance testing conducted during this research indicates that TLC testing can be used to  compare distances traveled by analytes when exposed to various solvent mobile phases” This statement should be supported better in the text of the paper

“The data gathered from this study can be further evaluated using  high-performance liquid chromatography to gather more effective quantitative data about the solvent and analyte interactions.” This sentence should be avoided, no evidences for that was given in the paper.

Author Response

To MDPI Separations Reviewers,

Thank you for your letter regarding our manuscript “Designing Safer Solvents to Replace Methylene Chloride for Liquid Chromatography Applications Using Thin Layer Chromatography as a Screening Tool” (MDPI Separations). We are grateful for the constructive feedback you have provided. We have carefully reviewed your feedback and have made changes to the manuscript item by item to address all your comments.  Please find the proposed corrections attached.

Author Response File: Author Response.pdf

Reviewer 3 Report

1. Green metrics analysis should be presented to demonstrate that the proposed alternatives are indeed greener than the use of DCM. Solvent blends are notoriously difficult to recover compared to single solvents. The difficulty in recovering solvent blends entails higher energy demand which ultimately undermine the benefits.
2. The authors state that ‘there are many problematic solvents for which a green substitute does not exist including DCM’. However, there are many attempts in the literature to replace DCM in many fields including chromatography. These efforts should be mentioned in the manuscript and their shortcomings should be discussed if any (10.1039/C2GC36064K).
3. A general review about the greenness of solvents and their application should be mentioned so the interested readers can further dig into the topic (10.1016/B978-0-12-809270-5.00020-0).
4. There are many fields where the replacement of chlorinated solvents is necessary and efforts have been made lately. A short discussion on this should be added with examples to widen the scope and background of the research (10.1021/op990183d; 10.1039/D1GC00778E). It seems that the results presented in the manuscript is not restricted to the replacement of DCM in chromatography only.
5. The conclusion section is too vague and short. Elaborate more on the main findings and potential impact of the work. How has the field been advanced? What are the next steps? Also, the main research findings should be summarized in quantitative statements as well.
6. The title has ’pharmaceutical industry’ but the work lacks any pharmaceutical industrial input. Remove from the title or clarify what makes the work in particular ‘industry’ relevant opposed to any other research in the field.

Author Response

To MDPI Separations Reviewers,

Thank you for your letter regarding our manuscript “Designing Safer Solvents to Replace Methylene Chloride for Liquid Chromatography Applications Using Thin Layer Chromatography as a Screening Tool” (MDPI Separations). We are grateful for the constructive feedback you have provided. We have carefully reviewed your feedback and have made changes to the manuscript item by item to address all your comments.  Please find the proposed corrections attached.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The paper has been improved in accordance with reviewer´s suggestions.

In my opinion the new version can be published in its present form

Reviewer 3 Report

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