Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis
, Valentina Sobornova 1, Valeriya Mulloyarova 2, Konstantin Belov 1, Alexey Dyshin 1, LuÃs Batista de Carvalho 3, Peter Tolstoy 2 and Michael Kiselev 1
Round 1
Reviewer 1 Report
I read the manuscript "Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis" with great interest and I really appreciate the work done.
First of all, the methods involved in the study of mefenamic acid conformers are originals being focused on a good correlation structure-properties by means of solid state MAS NMR and 2D correlation spectra: T1-T2 RRCOSY and NOESY. The overall studies are well performed and supported by relevant references. The authors also revealed different conformers of MFA compound which is also a great achievement in understanding the interaction drug-matrix (silica aerogel). However, it would be a great interest to study the conformers equilibrium in phosphate buffer media in the release kinetics of this drug from silica aerogel matrix.
I consider that this paper fully deserves to be published in this special issue.
Author Response
Reviewer #1:
I read the manuscript "Exploring the Conformational Equilibrium of Mefenamic Acid Released from Silica Aerogels via NMR Analysis" with great interest and I really appreciate the work done.
First of all, the methods involved in the study of mefenamic acid conformers are originals being focused on a good correlation structure-properties by means of solid state MAS NMR and 2D correlation spectra: T1-T2 RRCOSY and NOESY. The overall studies are well performed and supported by relevant references. The authors also revealed different conformers of MFA compound which is also a great achievement in understanding the interaction drug-matrix (silica aerogel). However, it would be a great interest to study the conformers equilibrium in phosphate buffer media in the release kinetics of this drug from silica aerogel matrix.
I consider that this paper fully deserves to be published in this special issue.
Our response: Thank you for your thoughtful review and insightful comments. We agree that it would be of great interest to study the conformers equilibrium in phosphate buffer media in the release kinetics of this drug from silica aerogel matrix. We are currently in the process of conducting further experiments to explore this and will be sure to include the results in a future publication. We appreciate your feedback and are grateful for the opportunity to submit our work to this special issue.
Reviewer 2 Report
The manuscript by Khodov et al. reports a study of a TEOS-doped silica loaded with mefenamic acid. The loading of mefenamic acid was assisted by supercritical carbon dioxide.
The aim of this work was to study the effect of mefenamic acid on the kinetics of incorporation of supercritical carbon dioxide into the silica matrix and the effect of the matrix on the conformation of acid molecules released into supercritical carbon dioxide.
The topic of the study is relevant in the field and its motivation is justified.
However, I have critical remarks both on the style of presentation and on the scientific part of the manuscript.
1. The manuscript contains many grammatical errors, and one has to guess the meaning of some sentences.
See: „This process involves using high-pressure carbon dioxide to att ach the drug to a porous material, which increases its surface area and enhances its dissolution rate. “
“The dissolution rate of drugs is increased by adsorption in an amorphous state [10].”
„ Therefore, researchers are looking for ways to improve the form of mefenamic acid with the aim of repurposing it. “
2. A large difference in the intensities of the CH2 and CH3 groups of TEOS in Figure 1 is due to the presence of a SiOH signal at 1.8 ppm. (see doi.org/10.1021/jp907058y). The presence of mefenamic acid is not evident from the reported 1H NMR spectra. The color change shown in Figure A2 is a clearer indication of the acid adsorption and its interaction with the surface silanol groups. (see Asian J. Chem. /2009 / 21(1)/ pp 211-216/ https://faculty.ksu.edu.sa/sites/default/files/027-7412__217-226_%20(1).pdf)
3. A relaxation time of 2 s is insufficient to obtain a reliable Q3/Q4 ratio in 29Si NMR. (see doi.org/10.1021/jp073682m)
4. Figure 4 contradicts the equation 1. For large t, Delta_t must tend to Delta_0.
5. The effect of the acid on the RRCOSY spectrum is very small. It is necessary either to confirm that the measurement accuracy is sufficient for unambiguous conclusions, or to correct the text.
Author Response
Reviewer #2:
The manuscript by Khodov et al. reports a study of a TEOS-doped silica loaded with mefenamic acid. The loading of mefenamic acid was assisted by supercritical carbon dioxide.
The aim of this work was to study the effect of mefenamic acid on the kinetics of incorporation of supercritical carbon dioxide into the silica matrix and the effect of the matrix on the conformation of acid molecules released into supercritical carbon dioxide.
The topic of the study is relevant in the field and its motivation is justified.
Our response: Thank you for your review and your critical remarks. We have considered your comments and made the necessary manuscript changes. We have corrected the grammatical errors and clarified the meaning of some sentences. We have also included additional disscussion in the text regarding the presence of mefenamic acid in the 1H NMR spectra, the color change in Figure A2, and the effect of the acid on the RRCOSY spectrum. We have also adjusted the misprint in the indicated real experimental value of the relaxation time to 29Si NMR and corrected the y-axis label in Figure 4. We hope that these changes have addressed your concerns.
Round 2
Reviewer 2 Report
I have no more comments that would necessitate another review cycle.
