Quality by design approach for the formulation of bilayer tablets of domperidone and itopride in gastro esophageal reflux disease

Roshani Prajapati; Bhavna Kumar; Jagannath Sahoo; Shailendra Shakya; Diwya Kumar Lal

doi:10.7324/JAPS.2024.168489

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Abstract

In the current work, a bilayer tablet of itopride gastroretentive and domperidone immediate release formulation was developed showing the synergistic effect of gastric motility in gastroesophageal reflux disease, through antidopaminergic and antiacetylcholine stearic activities. A bilayer tablet of domperidone and itopride was optimized using quality by design and its product performance was analyzed. Itopride was designed to be gastroretentive and remains in the stomach for a longer period, providing sustained release. The domperidone layer was optimized by an empirical hit and trial method, while the itopride layer was optimized using the Box Behnken experimental design. Three independent variables were considered as hydroxypropyl methyl cellulose K 100 M, xanthum gum, and Carbomer 974 with dependent variables like floating lag time, swellable index, and percentage drug release at 24 hours. Quality target product profile and critical quality attributes were studied which helps in an effective way to develop bilayer tablets. The excipients were chosen based on the time taken by medicaments to be released and the quantity was optimized according to Handbook of Pharmaceutical Excipient. From the optimization processes, DF5 and IH2 were selected as optimized composition for the formulation of domperidone and itopride layer of bilayer tablet respectively. The bilayer tablets were formulated in 16 × 8.26 mm oblong plain biconcave die and punch. The in-vitro drug release of domperidone was 99.39% in 30 minutes and itopride was 27.50%, 53.45%, and 93.65% at 4, 16, and 24 hours respectively.

Keyword: Quality by design bilayer tablets immediate release gastro-retentive quality control

Citation:

Prajapati R, Kumar B, Sahoo J, Shakya S, Lal DK. Quality by design approach for the formulation of bilayer tablets of domperidone and itopride in gstro esophageal refluxFirstdisease. J Appl Pharm Sci. 2024. Online First. http://doi.org/10.7324/JAPS.2024.168489

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

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2. Chapelle N, Ben Ghezala I, Barkun A, Bardou M. The pharmacotherapeutic management of gastroesophageal reflux disease (GERD). Expert Opin Pharmacother. 2021;22(2):219-27. https://doi.org/10.1080/14656566.2020.1817385
3. Clarrett DM, Hachem C. Gastroesophageal reflux disease (GERD). Mo Med. 2018;115(3):214-8.
4. Poddar U. Gastroesophageal reflux disease (GERD) in children. Paediatr Int Child Health. 2019;39(1):7-12. https://doi.org/10.1080/20469047.2018.1489649
5. Silvers D, Kipnes M, Broadstone V, Patterson D, Quigley EM, McCallum R, et al. Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. Clin Ther. 1998;20(3):438-53. https://doi.org/10.1016/S0149-2918(98)80054-4
6. Gupta AM, Belgamwar AV, Wake PS, Rathi TP, Mundhada D. Design and development of hydrodynamically balanced tablet of itopride. J Chem Pharm Res. 2011;3(6):856-64.
7. Ma J, Yuan L-H, Ding M-J, Zhang J, Zhang Q, Xu Q-W, et al. Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study. Pharmacol Res. 2009;59(3):189-93. https://doi.org/10.1016/j.phrs.2008.11.007
8. Porwal A, Dwivedi H, Pathak K. Gastroretentive bilayer film for sustained release of atorvastatin calcium and immediate release of amlodipine besylate: pharmaceutical, pharmacokinetic evaluation, and IVIVC. Pharma Dev Technol. 2020;25(4):416-31. https://doi.org/10.1080/10837450.2019.1705486
9. Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics. 2019;11(4):193. https://doi.org/10.3390/pharmaceutics11040193
10. Iglesias N, Galbis E, Romero-Azogil L, Benito E, Lucas R, García-Martín MG, et al. In-depth study into polymeric materials in low-density gastroretentive formulations. Pharmaceutics. 2020;12(7):636. https://doi.org/10.3390/pharmaceutics12070636
11. Kim B, Byun Y, Lee EH. DoE-based design of a simple but efficient preparation method for a non-effervescent gastro-retentive floating tablet containing metformin HCl. Pharmaceutics. 2021;13(8):1225. https://doi.org/10.3390/pharmaceutics13081225
12. Juran JM. Juran on quality by design: the new steps for planning quality into goods and services. New York, NY: Simon and Schuster; 1992.
13. Food and Drug Administration. Pharmaceutical development Q8(R2). Food and Drug Administration; 2009. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q8r2-pharmaceutical-development
14. ICH. Validation of analytical procedures: text and methodology Q2(R1). Food and Drug Administration; 2005. Available from: https://database.ich.org/sites/default/files/Q2%28R1%29%20Guideline.pdf
15. ICH. Pharmaceutical quality system Q10. Food and Drug Administration; 2010. Available from: https://www.fda.gov/media/71553/download
16. Pramod K, Tahir MA, Charoo NA, Ansari SH, Ali J. Pharmaceutical product development: a quality by design approach. Int J Pharma Investig. 2016;6(3):129-38. https://doi.org/10.4103/2230-973X.187350
17. Dholariya YN, Bansod YB, Vora RM, Mittal SS, Shirsat AE, Bhingare CL. Design and optimization of bilayered tablet of hydrochlorothiazide using the quality-by-design approach. Int J Pharm Investig. 2014;4(2):93. https://doi.org/10.4103/2230-973X.133058
18. Malladi M, Jukanti R. Formulation development and evaluation of a novel bi-dependent clarithromycin gastroretentive drug delivery system using Box-Behnken design. J Drug Deliv Sci Technol. 2016;35:134-45. https://doi.org/10.1016/j.jddst.2016.06.003
19. Won DH, Park H, Ha E-S, Kim H-H, Jang SW, Kim M-S. Optimization of bilayer tablet manufacturing process for fixed dose combination of sustained release high-dose drug and immediate release low-dose drug based on quality by design (QbD). Int J Pharm. 2021;605:120838. https://doi.org/10.1016/j.ijpharm.2021.120838
20. Jadhav SB, Mali A, Rajeghadage S, Bathe R. Formulation and evaluation of immediate release tablets of imipramine hydrochloride. Int J Biomed Adv Res. 2014;5(11):559-65. https://doi.org/10.7439/ijbar.v5i11.980
21. Marshal K. Compression and consolidation of powdered solids. In: Lachman L, Lieberman HA, Kanig JL, editors. The theory and practice of industrial pharmacy. Mumbai, India: Varghese Publishing House; 1987.
22. Sarfraz RM, Khan HU, Mahmood A, Ahmad M, Maheen S, Sher M. Formulation and evaluation of mouth disintegrating tablets of atenolol and atorvastatin. Indian J Pharm Sci. 2015;77(1):83-90. https://doi.org/10.4103/0250-474X.151602
23. Behera A, Nayak A, Mohanty B, Barik B. Development and optimization of losartan potassium tablets. Int J Appl Pharma. 2010;2:15-9.
24. Ratnaparkhi MP. Formulation and development of floating drug delivery of itopride HCl. J Drug Deliv Ther. 2013;3(4):222-8. https://doi.org/10.22270/jddt.v3i4.579
25. Tak JW, Gupta B, Thapa RK, Woo KB, Kim SY, Go TG, et al. Preparation and optimization of immediate release/sustained release bilayered tablets of loxoprofen using Box-Behnken design. AAPS PharmSciTech. 2017;18:1125-34. https://doi.org/10.1208/s12249-016-0580-5
26. Remya P, Damodharan N, Sulakshan Kumar C. Formulation and evaluation of bilayered tablets of ibuprofen and methocarbamol. Int J PharmTech Res. 2010;2(2):1250-55.
27. Joshna B, Sirisolla JD. Formulation, evaluation and comparison of mesalamine compression coated tablets by using natural and semi synthetic polymers. J Drug Deliv Therap. 2022;12(4-S):33-9. https://doi.org/10.22270/jddt.v12i4-S.5606
28. González R, Peña MÁ, Torres NS, Torrado G. Design, development, and characterization of amorphous rosuvastatin calcium tablets. PLoS One. 2022;17(3):e0265263. https://doi.org/10.1371/journal.pone.0265263
29. Nagar P, Singh K, Chauhan I, Verma M, Yasir M, Khan A, et al. Orally disintegrating tablets: formulation, preparation techniques and evaluation. J Appl Pharma Sci. 2011;1(4):35-45.
30. Nigusse B, Gebre-Mariam T, Belete A. Design, development and optimization of sustained release floating, bioadhesive and swellable matrix tablet of ranitidine hydrochloride. PLoS One. 2021;16(6):e0253391. https://doi.org/10.1371/journal.pone.0253391
31. Jagdale SC, Agavekar AJ, Pandya SV, Kuchekar BS, Chabukswar AR. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride. AAPS PharmSciTech. 2009;10(3):1071-9. https://doi.org/10.1208/s12249-009-9300-8
32. Sawant R, Bhangale L, Joshi R, Lanke P. Validated spectrophotometric methods for simultaneous estimation of Paracetamol, domperidone and tramadol HCl in pure and tablet dosage form. J Chem Metrol. 2010;4(1):21.
33. Afzal M, Muddassir M, Alarifi A, Ansari MT. Box-Behnken assisted validation and optimization of an RP-HPLC method for simultaneous determination of domperidone and lansoprazole. Separations. 2021;8(1):5. https://doi.org/10.3390/separations8010005
34. Perumal SS, Ekambaram SP, Raja S. Analytical method development and validation of simultaneous estimation of rabeprazole, pantoprazole, and itopride by reverse-phase high-performance liquid chromatography. J Food Drug Anal. 2014;22(4):520-6. https://doi.org/10.1016/j.jfda.2014.05.003
35. Zate SU, Kothawade PI, Gajbe JW, Pramod AS, Boraste SS. Spectrophotometric method development and validation of itopride hydrochloride in bulk and dosage form. Int J Drug Deliv. 2010;2(4):340-3. https://doi.org/10.5138/ijdd.2010.0975.0215.02046
36. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217-23.
37. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-33. https://doi.org/10.1016/S0928-0987(01)00095-1
38. Higuchi T. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145-9. https://doi.org/10.1002/jps.2600521210
39. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25-35. https://doi.org/10.1016/0378-5173(83)90064-9
40. Bohrey S, Chourasiya V, Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Converg. 2016;3(1):3. https://doi.org/10.1186/s40580-016-0061-2
41. Remington JP. Remington: the science and practice of pharmacy. In: Troy DB, Beringer P, editors. Baltimore, MD: Lippincott Williams & Wilkins; 2006.

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1. Savarino E, Zentilin P, Marabotto E, Bodini G, Della Coletta M, Frazzoni M, et al. A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD). Expert Opin Pharmacother. 2017;18(13):1333-43. https://doi.org/10.1080/14656566.2017.1361407

2. Chapelle N, Ben Ghezala I, Barkun A, Bardou M. The pharmacotherapeutic management of gastroesophageal reflux disease (GERD). Expert Opin Pharmacother. 2021;22(2):219-27. https://doi.org/10.1080/14656566.2020.1817385

3. Clarrett DM, Hachem C. Gastroesophageal reflux disease (GERD). Mo Med. 2018;115(3):214-8.

4. Poddar U. Gastroesophageal reflux disease (GERD) in children. Paediatr Int Child Health. 2019;39(1):7-12. https://doi.org/10.1080/20469047.2018.1489649

5. Silvers D, Kipnes M, Broadstone V, Patterson D, Quigley EM, McCallum R, et al. Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. Clin Ther. 1998;20(3):438-53. https://doi.org/10.1016/S0149-2918(98)80054-4

6. Gupta AM, Belgamwar AV, Wake PS, Rathi TP, Mundhada D. Design and development of hydrodynamically balanced tablet of itopride. J Chem Pharm Res. 2011;3(6):856-64.

7. Ma J, Yuan L-H, Ding M-J, Zhang J, Zhang Q, Xu Q-W, et al. Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study. Pharmacol Res. 2009;59(3):189-93. https://doi.org/10.1016/j.phrs.2008.11.007

8. Porwal A, Dwivedi H, Pathak K. Gastroretentive bilayer film for sustained release of atorvastatin calcium and immediate release of amlodipine besylate: pharmaceutical, pharmacokinetic evaluation, and IVIVC. Pharma Dev Technol. 2020;25(4):416-31. https://doi.org/10.1080/10837450.2019.1705486

9. Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics. 2019;11(4):193. https://doi.org/10.3390/pharmaceutics11040193

10. Iglesias N, Galbis E, Romero-Azogil L, Benito E, Lucas R, García-Martín MG, et al. In-depth study into polymeric materials in low-density gastroretentive formulations. Pharmaceutics. 2020;12(7):636. https://doi.org/10.3390/pharmaceutics12070636

11. Kim B, Byun Y, Lee EH. DoE-based design of a simple but efficient preparation method for a non-effervescent gastro-retentive floating tablet containing metformin HCl. Pharmaceutics. 2021;13(8):1225. https://doi.org/10.3390/pharmaceutics13081225

12. Juran JM. Juran on quality by design: the new steps for planning quality into goods and services. New York, NY: Simon and Schuster; 1992.

13. Food and Drug Administration. Pharmaceutical development Q8(R2). Food and Drug Administration; 2009. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q8r2-pharmaceutical-development

14. ICH. Validation of analytical procedures: text and methodology Q2(R1). Food and Drug Administration; 2005. Available from: https://database.ich.org/sites/default/files/Q2%28R1%29%20Guideline.pdf

15. ICH. Pharmaceutical quality system Q10. Food and Drug Administration; 2010. Available from: https://www.fda.gov/media/71553/download

16. Pramod K, Tahir MA, Charoo NA, Ansari SH, Ali J. Pharmaceutical product development: a quality by design approach. Int J Pharma Investig. 2016;6(3):129-38. https://doi.org/10.4103/2230-973X.187350

17. Dholariya YN, Bansod YB, Vora RM, Mittal SS, Shirsat AE, Bhingare CL. Design and optimization of bilayered tablet of hydrochlorothiazide using the quality-by-design approach. Int J Pharm Investig. 2014;4(2):93. https://doi.org/10.4103/2230-973X.133058

18. Malladi M, Jukanti R. Formulation development and evaluation of a novel bi-dependent clarithromycin gastroretentive drug delivery system using Box-Behnken design. J Drug Deliv Sci Technol. 2016;35:134-45. https://doi.org/10.1016/j.jddst.2016.06.003

19. Won DH, Park H, Ha E-S, Kim H-H, Jang SW, Kim M-S. Optimization of bilayer tablet manufacturing process for fixed dose combination of sustained release high-dose drug and immediate release low-dose drug based on quality by design (QbD). Int J Pharm. 2021;605:120838. https://doi.org/10.1016/j.ijpharm.2021.120838

20. Jadhav SB, Mali A, Rajeghadage S, Bathe R. Formulation and evaluation of immediate release tablets of imipramine hydrochloride. Int J Biomed Adv Res. 2014;5(11):559-65. https://doi.org/10.7439/ijbar.v5i11.980

21. Marshal K. Compression and consolidation of powdered solids. In: Lachman L, Lieberman HA, Kanig JL, editors. The theory and practice of industrial pharmacy. Mumbai, India: Varghese Publishing House; 1987.

22. Sarfraz RM, Khan HU, Mahmood A, Ahmad M, Maheen S, Sher M. Formulation and evaluation of mouth disintegrating tablets of atenolol and atorvastatin. Indian J Pharm Sci. 2015;77(1):83-90. https://doi.org/10.4103/0250-474X.151602

23. Behera A, Nayak A, Mohanty B, Barik B. Development and optimization of losartan potassium tablets. Int J Appl Pharma. 2010;2:15-9.

24. Ratnaparkhi MP. Formulation and development of floating drug delivery of itopride HCl. J Drug Deliv Ther. 2013;3(4):222-8. https://doi.org/10.22270/jddt.v3i4.579

25. Tak JW, Gupta B, Thapa RK, Woo KB, Kim SY, Go TG, et al. Preparation and optimization of immediate release/sustained release bilayered tablets of loxoprofen using Box-Behnken design. AAPS PharmSciTech. 2017;18:1125-34. https://doi.org/10.1208/s12249-016-0580-5

26. Remya P, Damodharan N, Sulakshan Kumar C. Formulation and evaluation of bilayered tablets of ibuprofen and methocarbamol. Int J PharmTech Res. 2010;2(2):1250-55.

27. Joshna B, Sirisolla JD. Formulation, evaluation and comparison of mesalamine compression coated tablets by using natural and semi synthetic polymers. J Drug Deliv Therap. 2022;12(4-S):33-9. https://doi.org/10.22270/jddt.v12i4-S.5606

28. González R, Peña MÁ, Torres NS, Torrado G. Design, development, and characterization of amorphous rosuvastatin calcium tablets. PLoS One. 2022;17(3):e0265263. https://doi.org/10.1371/journal.pone.0265263

29. Nagar P, Singh K, Chauhan I, Verma M, Yasir M, Khan A, et al. Orally disintegrating tablets: formulation, preparation techniques and evaluation. J Appl Pharma Sci. 2011;1(4):35-45.

30. Nigusse B, Gebre-Mariam T, Belete A. Design, development and optimization of sustained release floating, bioadhesive and swellable matrix tablet of ranitidine hydrochloride. PLoS One. 2021;16(6):e0253391. https://doi.org/10.1371/journal.pone.0253391

31. Jagdale SC, Agavekar AJ, Pandya SV, Kuchekar BS, Chabukswar AR. Formulation and evaluation of gastroretentive drug delivery system of propranolol hydrochloride. AAPS PharmSciTech. 2009;10(3):1071-9. https://doi.org/10.1208/s12249-009-9300-8

32. Sawant R, Bhangale L, Joshi R, Lanke P. Validated spectrophotometric methods for simultaneous estimation of Paracetamol, domperidone and tramadol HCl in pure and tablet dosage form. J Chem Metrol. 2010;4(1):21.

33. Afzal M, Muddassir M, Alarifi A, Ansari MT. Box-Behnken assisted validation and optimization of an RP-HPLC method for simultaneous determination of domperidone and lansoprazole. Separations. 2021;8(1):5. https://doi.org/10.3390/separations8010005

34. Perumal SS, Ekambaram SP, Raja S. Analytical method development and validation of simultaneous estimation of rabeprazole, pantoprazole, and itopride by reverse-phase high-performance liquid chromatography. J Food Drug Anal. 2014;22(4):520-6. https://doi.org/10.1016/j.jfda.2014.05.003

35. Zate SU, Kothawade PI, Gajbe JW, Pramod AS, Boraste SS. Spectrophotometric method development and validation of itopride hydrochloride in bulk and dosage form. Int J Drug Deliv. 2010;2(4):340-3. https://doi.org/10.5138/ijdd.2010.0975.0215.02046

36. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217-23.

37. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-33. https://doi.org/10.1016/S0928-0987(01)00095-1

38. Higuchi T. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145-9. https://doi.org/10.1002/jps.2600521210

39. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1):25-35. https://doi.org/10.1016/0378-5173(83)90064-9

40. Bohrey S, Chourasiya V, Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Converg. 2016;3(1):3. https://doi.org/10.1186/s40580-016-0061-2

41. Remington JP. Remington: the science and practice of pharmacy. In: Troy DB, Beringer P, editors. Baltimore, MD: Lippincott Williams & Wilkins; 2006.