Review Reports - Conversion of Lignocellulosic Corn Agro-Waste into Cellulose Derivative and Its Potential Application as Pharmaceutical Excipient

Round 1

Reviewer 1 Report

The research manuscript entitled “Conversion of lignocellulosic corn agro-waste into cellulose derivative and its potential application as pharmaceutical excipient” by Rahman et al. is a very interesting research work in the field of lignocellulosic residues valorization. In the present work, holocellulose is properly isolated from corn waste as well as converted into carboxymethyl cellulose. In the same way, characterization carried out in both holocellulose and CMC samples is complete to support the correct obtention of CMC. Additionally, authors propose the use of corn waste derived-CMC to be apply as a pharmaceutical excipient comparing its properties with commercial CMC. However, some modifications need to be done before publication of the manuscript, so I recommend this manuscript for publication after some minor revisions.

GENERAL COMMENTS

The entire manuscript needs to be deeply revised in order to improve the language and the terms used. The English in some parts of the manuscript is very poor and needs to be checked to better understand what authors want to convey. Moreover, there are a considerable amount of spelling errors: i.e. “as corn (Zea mays” is one of the most vital and abundant cereal crop that is cultivated…”; “for corn production in the period of 2012-2017…”; “…processing of mature corn produces significant amount of ”; “temperature, reaction time and the steps…”; “To the best of our knowledge, no report has been found…”; “Defective parts and foreign materials from the corn wastes…”; “105 ºC”; “This unit was quite tough to break down at the referred temperature. Therefore, we assume that CMC should have higher stability than holocellulose (mass basis).”
Please check the use of the terms “waste” and “residues”. Usually, “residues” is used when is referred to a mixture of different species (i.e. lignocellulosic residues), whereas “waste” is used for a specific one (i.e. corn waste). Unify then all over the manuscript.

RESULTS AND DISCUSSION

Could authors estimate the size of isolated holocellulose and CMC from the SEM analysis?
Regarding the analysis carried out to suggest the application of the produced CMC as a pharmaceutical excipient, authors slightly mention the influence of the moisture content on the flowability of the powder. Flowability is critical to tableting therefore I recommend to discuss this parameter. Some authors have established in literature that moisture content higher than 3-5% is directly related with a strong decrease in tensile strength. Since the authors have not developed the tablets and therefore have not measured the tensile strength, I recommend discussing how an 11% moisture content in the prepared CMC would affect the proposed application.
Please standardize the decimals in Table 2.

Author Response

We thank the reviewer for the constructive comments and suggestions to improve the manuscript quality. We have now considered all of the concerns and acted accordingly. We have used track change option in the revised manuscript to show the necessary changes by different color.

Response to Reviewer-1 Comments and Suggestions

Overall Comments:

Response: We thank the reviewer for making a good overview of our manuscript and also for the positive comments and suggestions to improve the manuscript quality.

GENERAL COMMENTS

Comments-1: The entire manuscript needs to be deeply revised in order to improve the language and the terms used. The English in some parts of the manuscript is very poor and needs to be checked to better understand what authors want to convey. Moreover, there are a considerable amount of spelling errors: i.e. “as corn (Zea mays” is one of the most vital and abundant cereal crop that is cultivated…”; “for corn production in the period of 2012-2017…”; “…processing of mature corn produces significant amount of ”; “temperature, reaction time and the steps…”;“To the best of our knowledge, no report has been found…”; “Defective parts and foreign materials from the corn wastes…”; “105 ºC”; “This unit was quite tough to break down at the referred temperature. Therefore, we assume that CMC should have higher stability than holocellulose (mass basis).”

Response: Thank you very much to pointing out the grammatical errors. We have revised the whole manuscript to avoid further grammatical errors. In addition, we have also revised the whole manuscript to correct the spelling errors and others in the revised manuscript.

Comment-2: Please check the use of the terms “waste” and “residues”. Usually, “residues” is used when is referred to a mixture of different species (i.e. lignocellulosic residues), whereas “waste” is used for a specific one (i.e. corn waste). Unify then all over the manuscript.

Response: Thank you very much to correct the term using. We have now replaced the term “residues” with “waste” where applicable in the revised manuscript according to reviewer suggestion.

RESULTS AND DISCUSSION

Comment-3: Could authors estimate the size of isolated holocellulose and CMC from the SEM analysis?

Response: Reviewer is right that SEM image can be used for the measurement of the size of any particles. According to the suggestion of this reviewer, we have found that the size of the particles of holocellulose and CMC were in the range of 1.0-3.5 and 1.5-3.5 mm (approximately), respectively. Relevant discussion has been added in the revised manuscript.

Comment-6: Regarding the analysis carried out to suggest the application of the produced CMC as a pharmaceutical excipient, authors slightly mention the influence of the moisture content on the flowability of the powder. Flowability is critical to tableting therefore I recommend to discuss this parameter.

Response: We have discussed elaborately about the role of moisture content on flow property of excipient in the revised manuscript according to the suggestion of this reviewer.

Comment-7: Some authors have established in literature that moisture content higher than 3-5% is directly related with a strong decrease in tensile strength. Since the authors have not developed the tablets and therefore have not measured the tensile strength, I recommend discussing how an 11% moisture content in the prepared CMC would affect the proposed application.

Response: Yes, reviewer is correctly pointed out the matter that 3-5% moister content is required for getting higher tensile strength of the tablet during formulation and compression. Actually, according to our the TGA result, the moisture content of CMC was 11%. So, the confusion may rise from this data. However, for pharmaceutical excipient application, moisture content of the CMC was reduced to 0.94-1.36%. So, we hope, we meet the required standard as require for table compression.

Comment-8: Please standardize the decimals in Table 2.

Response: We have now standardized the Table number 2 according to the suggestion of this reviewer.

Author Response File: Author Response.docx

Reviewer 2 Report

In this work, the authors suggested an experimental process to isolate holocellulose from corn waste, and to convert it to carboxymethyl cellulose (CMC). Subsequently, the prepared CMC was evaluated successfully to be used as pharmaceutical excipients.

It is very original and interesting. Before the publication, some aspects need minor improvements such as:

Introduction: the industrial application of this study isn’t clear. Authors have to deepen the potential industrial applications of their research. First with specific bibliography analysis about the industrial needs of the research section of the work, then describing the final purpose of the work done, in terms of industrial application;
Introduction: Nothing possible valorization of the lignocellulosic materials was presented in the work. In order to consider other alternative valorization processes, a brief analysis of lignocellulosic biorefineries has to be touched on (e.g., Giuliano A, Barletta D, De Bari I, Poletto M. Techno-economic assessment of a lignocellulosic biorefinery co-producing ethanol and xylitol or furfural. Comput Aided Chem Eng 2018:585–90. doi:dx.doi.org/10.1016/B978-0-444-64235-6.50105-4);
Introduction: a new Figure to show the chemical structure of holocellulose and CMC can help the reader to understand better the chemical process authors want to present in the work;
Material and Methods: nothing literature analysis on lignocellulose biomass pretreatment methods was described. The experimental methods to convert the lignocellulosic structure to cellulose/holocellulose have to be supported by previous literature works. Organosolv, dilute acid, LHW, etc. are an example of pretreatment processes to separate lignin, cellulose and hemicellulose (Rodrigues Gurgel da Silva A, Giuliano A, Errico M, Rong B-G, Barletta D. Economic value and environmental impact analysis of lignocellulosic ethanol production: assessment of different pretreatment processes. Clean Technol Environ Policy 2019;21:637–54. doi:https ://doi.org/10.1007/s1009 8-018-01663 -z.);
Material and Methods: in expressions (1) and (2) “W” and “W₀” symbols were used to indicate two different matters. Authors should show new symbols for each mathematical expression in order to facilitate the readers;
Conclusions: add a description concerning how the obtained results can improve the current industrial application of biobased pharmaceuticals excipients.

Author Response

Response to Reviewer-2 Comments and Suggestions

Overall Comments: In this work, the authors suggested an experimental process to isolate holocellulose from corn waste, and to convert it to carboxymethyl cellulose (CMC). Subsequently, the prepared CMC was evaluated successfully to be used as pharmaceutical excipients. It is very original and interesting. Before the publication, some aspects need minor improvements such as.

Response: We thank the reviewer for making a good overview of our manuscript and also for the positive comments and suggestions to improve the manuscript quality.

Specific Comments:

Comment-1: Introduction: the industrial application of this study isn’t clear. Authors have to deepen the potential industrial applications of their research. First with specific bibliography analysis about the industrial needs of the research section of the work, then describing the final purpose of the work done, in terms of industrial application;

Response: We value the reviewer concern about industrial application or real application of any research for its practical benefits to the end users. Subsequently, the prepared CMC was evaluated successfully to be used as a pharmaceuticals excipient. We believe, the produced CMC can have future application for making tablet as its properties are strongly matched with the real pharmaceutical excipients. Anyway, we have now added more discussion in the introduction section to make it clearer to the readers.

Comment-2: Introduction: Nothing possible valorization of the lignocellulosic materials was presented in the work. In order to consider other alternative valorization processes, a brief analysis of lignocellulosic bio-refineries has to be touched on (e.g., Giuliano A, Barletta D, De Bari I, Poletto M. Techno-economic assessment of a lignocellulosic biorefinery co-producing ethanol and xylitol or furfural. Comput. Aided Chem. Eng. 2018:585–90. doi:dx.doi.org/10.1016/B978-0-444-64235-6.50105-4);

Response: We thank the reviewer for the suggestion. According to the reviewer suggestion, we have now added few description of conversion of lignocellulosic into biorefineries. In addition, we have taken many information from the suggested paper and cited the paper (new reference number 6) accordingly in the revised manuscript.

Comment-3: Introduction: a new Figure to show the chemical structure of holocellulose and CMC can help the reader to understand better the chemical process authors want to present in the work.

Response: Thanks for the concern. Actually, we added the chemical structure of holocellulose and CMC in the figure. Anyway, we have now clearly mention in the introduction.

Comment-4: Material and Methods: nothing literature analysis on lignocellulose biomass pretreatment methods was described. The experimental methods to convert the lignocellulosic structure to cellulose/holocellulose have to be supported by previous literature works. Organic solvent, dilute acid, LHW, etc. are an example of pretreatment processes to separate lignin, cellulose and hemicellulose (Rodrigues Gurgel da Silva A, Giuliano A, Errico M, Rong B-G, Barletta D. Economic value and environmental impact analysis of lignocellulosic ethanol production: assessment of different pretreatment processes. Clean Technol Environ Policy 2019 ;21: 637–54. doi:https ://doi.org/10.1007/s1009 8-018-01663 -z.);

Response: Thank you very much for the recommendation. We have now added the relevant information in the section 2.5 in the revised manuscript with citing (new reference number 21) the suggested article.

Comment-5: Material and Methods: in expressions (1) and (2) “W” and “W₀” symbols were used to indicate two different matters. Authors should show new symbols for each mathematical expression in order to facilitate the readers;

Response: According to the suggestion of this reviewer, we have changed the symbols in the revised manuscript.

Comment-6: Conclusions: add a description concerning how the obtained results can improve the current industrial application of biobased pharmaceuticals excipients.

Response: According to the suggestion of this reviewer, we have now added a description in the conclusion part regarding the industrial application of the bio-based pharmaceutical excipients.

Author Response File: Author Response.docx