Design, development and optimization of sustained release floating, bioadhesive and swellable matrix tablet of ranitidine hydrochloride

Birhanu Nigusse; Tsige Gebre-Mariam; Anteneh Belete

doi:10.1371/journal.pone.0253391

Peer Review History

Original SubmissionNovember 30, 2020
10 Mar 2021 Decision Letter - Vineet Kumar Rai, Editor PONE-D-20-37614 Design, Development and Optimization of Sustained Release Floating, Bioadhesive and Swellable Matrix Tablet of Ranitidine Hydrochloride PLOS ONE Dear Dr. Gebre-Mariam, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by 20th March 2021. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: 1. I read this manuscript and I think that the paper is well written. Excellent contribution in terms of content and overall descriptions. The authors well described the Formulation development and evaluation of floating tablet. The tables and figures are good although I have some concerns about the resolution of the figures. 2. I suggest the authors to go through the whole content thoroughly to avoid any phrase and alignment problems and grammatical error that may influence the convey of idea. 3. please mention the Pos hoc test performed along with ANOVA in statistical analysis section. 4. Please mention at what point NaHCO3 was added during tablet formulation in methodology section. 5. Can author explained the relevance of ex vivo mucoadhesion time as formulation is floating type. 6. What is the rationale to do swelling test till 12 hrs. Discuss in detail regading effect of polymer and NaHCO3 concentration on swelling and bioadhesion with relevant references of similar work.. 7. Include standard deviation in table 4. 8. Elaborate drug release discussion with relevant references. 9. Author are suggest to cite more recent and relevant references. Reviewer #2: Manuscript Number: PONE-D-20-37614 Article Type: Research Article Full Title: Design, Development and Optimization of Sustained Release Floating, Bioadhesive and Swellable Matrix Tablet of Ranitidine Hydrochloride Dear Authors The present study was to attempt a SR tablet of Ranitidine based on Bio-adhesion mechanism. Study seems to be OK., but not in detailed layout., which was questionable to be published in Plos One. However, results were reported in GOOD state. The final decision will be taken by Eic. I am writing my comments below: In Introduction, the actual biopharmaceutical problems of Ranitidine were missing. What is the rationale of preparing its swellable tablet should be mentioned in the Introduction In CCD Design, α-value and design space for the developed formulations? The polynomial equations mentioned by the authors were not in quadratic state, as mentioned in statistical analysis PRESS value seems to be higher in the mathematical models? A justification is needed What is desirability value of optimized formulation? A graphical optimization graph should be provided? Major characterization studies have been done by the Authors, however a factual discussion is missing What is the rationale of doing the release profile of preliminary batches of CDD? What is the floatation behavior of optimized formulation Overall, the study is not novel, but the presentation is OK ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: Yes:** ok [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0253391.r001
Revision 1
25 Mar 2021 Author Response Rebuttal letter We thank the editor and the two reviewers for their comments on our manuscript titled “Design, Development and Optimization of Sustained Release Floating, Bioadhesive and Swellable Matrix Tablet of Ranitidine Hydrochloride (PONE-D-20-37614)”. The comments have significantly improved the quality of the manuscript. Below is our response, point-by-point, to comments forwarded by the academic editor and the reviewers. Sincerely, Prof. Tsige Gebre-Mariam On behalf of the authors Academic editor 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Authors’ response: PLOS ONE’s style requirements including are now fulfilled, those for file naming. 2. PLOS requires an ORCID ID for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. Authors’ response: The corresponding author has ORCID ID and it is validated in Editorial Manager. 3. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Authors’ response: We have made some changes in our financial disclosure section of the online submission and the updated statement is as follows: BN would like to thank the Regional Bioequivalence Center for sponsoring his MSc study, and School of Pharmacy, College of Health Sciences, Addis Ababa University for the financial and material support. BN would also like to thank Cadila Pharmaceutical Factory PLC for material support. 4. While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ Authors’ response: The figure files have been uploaded to the PACE and they now fulfill PLOS requirements. Reviewer #1 1. I read this manuscript and I think that the paper is well written. Excellent contribution in terms of content and overall descriptions. The authors well described the Formulation development and evaluation of floating tablet. The tables and figures are good although I have some concerns about the resolution of the figures. Authors’ response: The resolution of the figures is now improved and it fulfils PLOS requirements. 2. I suggest the authors to go through the whole content thoroughly to avoid any phrase and alignment problems and grammatical error that may influence the convey of idea. Authors’ response: The document has been reviewed and the introduction is beefed-up. 3. Please mention the Pos hoc test performed along with ANOVA in statistical analysis section. Authors’ response: Pos hoc test performed is now included in S2 Table 4. Please mention at what point NaHCO3 was added during tablet formulation in methodology section. Authors’ response: Since direct compression method was used in the preparation of the tablets, NaHCO3 was mixed together with ranitidine HCl, HPMC/NaCMC and MCC first and to this blend magnesium stearate and talc were then added and mixed. 5. Can author explain the relevance of ex vivo mucoadhesion time as formulation is floating type? Authors’ response: The formulation is floating, as well as bioadhesive, and swelling type. 6. What is the rationale to do swelling test till 12 hrs. Discuss in detail regarding effect of polymer and NaHCO3 concentration on swelling and bioadhesion with relevant references of similar work. Authors’ response: Percent swelling was conducted up to 12 h because the complete swelling was achieved at 12 h. The effects of polymer and NaHCO3 on bioadhesive and swelling characteristics of the formulations is discussed in detail with relevant references in the revised version. 7. Include standard deviation in table 4. Authors’ response: Standard deviation is now added to the table. 8. Elaborate drug release discussion with relevant references. Authors’ response: Drug release is more elaborated in the revised version. 9. Author are suggested to cite more recent and relevant references. Authors’ response: Recent and relevant references are added in the revised version. Reviewer #2 Dear Authors The present study was to attempt a SR tablet of Ranitidine based on Bio-adhesion mechanism. Study seems to be OK, but not in detailed layout, which was questionable to be published in Plos One. However, results were reported in GOOD state. The final decision will be taken by Eic. I am writing my comments below: Authors’ response: The mechanism is not only bio-adhesion, rather a combination of floating, bio-adhesion and swelling. In Introduction, the actual biopharmaceutical problems of Ranitidine were missing. What is the rationale of preparing its swellable tablet should be mentioned in the Introduction Authors’ response: The biopharmaceutical problems of ranitidine HCl have been discussed in the manuscript and this was the very reason for designing sustained release through different gastrortentive mechanisms (floating, bioadhesive and swelling). The rationale for swelling as well as for the combination of mechanisms is provided in the introduction. In CCD, α-value and design space for the developed formulations? The polynomial equations mentioned by the authors were not in quadratic state, as mentioned in statistical analysis Authors’ response: The α-value and design space are stated in Table 1. The polynomial equations were quadratic for floating lag time and t50%, and linear for the other response variables (bioadhesion strength, swelling index, drug release after 1 h and drug release after 12 h); consistent in the polynomial and statistical analysis. PRESS value seems to be higher in the mathematical models? A justification is needed What is desirability value of optimized formulation? A graphical optimization graph should be provided? Authors’ response: The fitness of the model was evaluated by the values of R2. As can be seen in S2 Table, R2 ranged from 0.952 - 0.981 for all selected mathematical model. The ‘Predicted R2’ value was in agreement with the ‘Adjusted R2’ value, the difference being less than 0.2, indicating the reliability of the model. Even though the PRESS values were apparently high in the mathematical models, the selected models have lower PRESS values. The desirability value of the optimized formulation is 0.856 (see line 379, revised manuscript) and the graphical optimization is now included in the revised manuscript (Fig 3). Major characterization studies have been done by the Authors, however a factual discussion is missing Authors’ response: The results that require elaboration are further discussed (effect of the concentration of polymer and effervescent agent on the release and gastro-retentive properties of the matrix tablets is discussed in more detail). Further discussion is also added in the mathematical models and statistical analysis in the CCD. Details of the optimized formulation (desirability value, overlay plot) are also incorporated in the revised version. What is the rationale of doing the release profile of preliminary batches of CCD? Authors’ response: The rationale of preliminary studies in CCD were to define the design space and to identify the critical formulation variables. What is the floatation behavior of optimized formulation? Authors’ response: The floating, bioadhesive, swelling and release characteristics of the optimized formulation were already included in the manuscript and summarized in S2 Fig. Overall, the study is not novel, but the presentation is OK Authors’ response: To our knowledge, there is no report on sustained release ranitidine HCl matrix tablets using a combination of three gastroretentive mechanisms, namely, floating, bio-adhesion and swelling. Hence, we believe this work will contribute significantly to the improvement of drug delivery. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0253391.r002
4 Jun 2021 Decision Letter - Vineet Kumar Rai, Editor Design, Development and Optimization of Sustained Release Floating, Bioadhesive and Swellable Matrix Tablet of Ranitidine Hydrochloride PONE-D-20-37614R1 Dear Dr. Gebre-Mariam, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Vineet Kumar Rai, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0253391.r003
Formally Accepted
18 Jun 2021 Acceptance Letter - Vineet Kumar Rai, Editor PONE-D-20-37614R1 Design, Development and Optimization of Sustained Release Floating, Bioadhesive and Swellable Matrix Tablet of Ranitidine Hydrochloride Dear Dr. Gebre-Mariam: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Vineet Kumar Rai Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0253391.r004

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