Formulation and evaluation of gastro-retentive in-situ gel of anti-ulcer drug misoprostol
DOI:
https://doi.org/10.56782/pps.441Keywords:
Peptic ulcer disease, Gastro-retentive in-situ gel, Misoprostol, Gellan gum, Calcium carbonate, Floating drug delivery, Controlled release, Stability studyAbstract
Background: Peptic ulcer disease (PUD) is a prevalent gastrointestinal disorder caused by an imbalance between protective and aggressive gastric factors. Misoprostol, a synthetic prostaglandin E1 analogue, is effective in ulcer management but has limitations such as rapid metabolism, low bioavailability, and frequent dosing. This study aimed to develop a gastro-retentive in-situ gel of misoprostol to enhance gastric retention and controlled drug release. Methods: The in-situ gel was formulated using gellan gum and calcium carbonate as key excipients. A 3² factorial design was employed to optimize floating lag time and in-vitro drug release. The formulations were evaluated for pH, viscosity, gelling capacity, floating behavior, drug content, and in-vitro drug release using a USP Type II dissolution apparatus in simulated gastric fluid (pH 1.2). Stability studies were conducted under accelerated conditions (40°C ± 2°C / 75% ± 5% RH) for six months. Results: The optimized formulation (LF5) exhibited a pH of 6.6, a floating lag time of 18.03 seconds, and a total floating time exceeding 6 hours, ensuring prolonged gastric retention. Drug content analysis confirmed 93.04% uniformity across batches. In-vitro drug release showed sustained drug release of 93.04% over 240 minutes. Stability studies demonstrated no significant changes in pH, floating behavior, or drug content, confirming formulation robustness. Conclusion: The gastro-retentive in-situ gel of misoprostol successfully enhanced gastric retention and controlled drug release. The optimized formulation exhibited rapid buoyancy, prolonged retention, and stability, making it a promising approach for improving misoprostol’s therapeutic efficacy in peptic ulcer management.
Downloads
References
1. Yegen, B. C. Lifestyle and Peptic Ulcer Disease. Curr. Pharm. Des. 2018, 24 (18), 2034–2040. DOI: 10.2174/1381612824666180510092303
2. Xie, X.; Ren, K.; Zhou, Z.; Dang, C.; Zhang, H. The Global, Regional and National Burden of Peptic Ulcer Disease from 1990 to 2019: A Population-Based Study. BMC Gastroenterol. 2022, 22 (1), Art. No: 58. DOI: 10.1186/s12876-022-02130-2
3. Shell, E. J. Pathophysiology of Peptic Ulcer Disease. Pharmacol. Clin. 2021, 6 (4), 603–611. DOI: 10.1016/j.cpha.2021.05.005
4. Srivastav, Y.; Kumar, V.; Srivastava, Y.; Kumar, M. Peptic Ulcer Disease (PUD), Diagnosis, and Current Medication-Based Management Options: Schematic Overview. J. Adv. Med. Pharm. Sci. 2023, 25 (11), 14–27. DOI: 10.9734/jamps/2023/v25i11651
5. Lee, S. P.; Sung, I.-K.; Kim, J. H.; Lee, S.-Y.; Park, H. S.; Shim, C. S. Risk Factors for the Presence of Symptoms in Peptic Ulcer Disease. Clin. Endosc. 2017, 50 (6), 578–584. DOI: 10.5946/ce.2016.129
6. Dunlap, J. J.; Patterson, S. Peptic Ulcer Disease. Gastroenterol. Nurs. 2019, 42 (5), 451–454. DOI: 10.1097/SGA.0000000000000478
7. Vigani, B.; Rossi, S.; Sandri, G.; Bonferoni, M. C.; Caramella, C. M.; Ferrari, F. Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes. Pharmaceutics 2020, 12 (9), Art. No: 859. DOI: 10.3390/pharmaceutics12090859
8. Shaikh, B. J.; Raut, I. D.; Nitalikar, M. M.; Mohite, S. K.; Magdum, C. S. An Overview on In-Situ Gel: A Novel Drug Delivery System. Int. J. Pharm. Sci. Nanotechnol. 2021, 15 (5), 6180–6189. DOI: 10.37285/ijpsn.2022.15.5.10
9. Wu, Y.; Liu, Y.; Li, X.; Kebebe, D.; Zhang, B.; Ren, J.; Lu, J.; Li, J.; Du, S.; Liu, Z. Research Progress of In-Situ Gelling Ophthalmic Drug Delivery System. Asian J. Pharm. Sci. 2019, 14 (1), 1–15. DOI: 10.1016/j.ajps.2018.04.008.
10. Kamada, T.; Satoh, K.; Itoh, T.; Ito, M.; Iwamoto, J.; Okimoto, T.; Kanno, T.; Sugimoto, M.; Chiba, T.; Nomura, S.; et al. Evidence-Based Clinical Practice Guidelines for Peptic Ulcer Disease 2020. J. Gastroenterol. 2021, 56 (4), 303–322. DOI: 10.1007/s00535-021-01769-0
11. Jadhav, S. P.; Dhakad, P. K.; Gupta, T.; Gilhotra, R. Formulation Development and Evaluation of Paliperidone Nanosuspension for Solubility Enhancement. Int. J. Appl. Pharm. 2024, 173–181. DOI: 10.22159/ijap.2024v16i4.51218
12. Wu, H.; Marwah, S.; Wang, P.; Wang, Q.; Chen, X. Misoprostol for Medical Treatment of Missed Abortion: A Systematic Review and Network Meta-Analysis. Sci. Rep. 2017, 7 (1), Art. No: 1664. DOI: 10.1038/s41598-017-01892-0
13. Raymond, E. G.; Harrison, M. S.; Weaver, M. A. Efficacy of Misoprostol Alone for First-Trimester Medical Abortion: A Systematic Review. Obstet. Gynecol. 2019, 133 (1), 137–147. DOI: 10.1097/AOG.0000000000003017
14. Salzberger, H.; Maul, H. Gutes Misoprostol, Böses Misoprostol – Oder Wie Ich Es Schaffe, Ein Medikament Mehr Als 100-Mal Teurer zu Machen? Geburtshilfe Frauenheilkd. 2022, 82 (05), 480–486. DOI: 10.1055/a-1664-0036
15. Szpot, P.; Wachełko, O.; Zawadzki, M. Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations. Toxics 2023, 11 (10), Art. No: 802. DOI: 10.3390/toxics11100802
16. Da Silva, J. W. V.; Duarte, M. L.; Ribeiro, J. I.; Kishishita, J.; Souza, A. T. M.; Leal, L. B.; De Castro, W. V.; De Santana, D. P.; Bedor, D. C. G. Development and Validation of a Stability-Indicating Method, Structural Elucidation of New Degradation Products from Misoprostol by LC–MS Time-of-Flight, and an Ex Vivo Study of Vaginal Permeation. Biomed. Chromatogr. 2024, 38 (8), Art. No: e5897. DOI: 10.1002/bmc.5897
17. Rojek, B.; Wesolowski, M. A Combined Differential Scanning Calorimetry and Thermogravimetry Approach for the Effective Assessment of Drug Substance–Excipient Compatibility. J. Therm. Anal. Calorim. 2023, 148 (3), 845–858. DOI: 10.1007/s10973-022-11849-9
18. Załuski, D.; Dubis, B.; Budzyński, W.; Jankowski, K. Applicability of the 3⁵–2 Fractional Factorial Design in Determining the Effects of Cultivation Factors on Hulless Oat. Agron. J. 2016, 108 (1), 205–218. DOI: 10.2134/agronj2014.0607
19. M. S. S.; Priya, S.; Maxwell, A. Formulation and Evaluation of Novel in Situ Gel of Lafutidine. Asian J. Pharm. Clin. Res. 2018, 11 (8), Art. No: 88. DOI: 10.22159/ajpcr.2018.v11i8.25582.
20. Siraj, S.N.; Vrushabha, J.G.; Khan, G. J. Design, Development and Evaluation of Gastric Floating In-Situ Gel of Piroxicam. Int. J. Pharm. Sci. Res. 2019, 11 (7), 3409-3416.
21. Juthi, A. Z.; Li, F.; Wang, B.; Alam, M. M.; Talukder, M. E.; Qiu, B. pH-Responsive Super-Porous Hybrid Hydrogels for Gastroretentive Controlled-Release Drug Delivery. Pharmaceutics 2023, 15 (3), Art. No: 816. DOI: 10.3390/pharmaceutics15030816
22. Vijayashree, R.; Priya, S.; Jyothi, D.; James, J. P. Formulation and Characterisation of Gastroretentive In Situ Gel Loaded with Glycyrrhiza glabra L. Extract for Gastric Ulcer. Int. J. Appl. Pharm. 2024, 16 (2), 76–85. DOI: 10.22159/ijap.2024v16i2.49033
23. Soni, A.; Kataria, M. K. Formulation and Evaluation of Floating In Situ Gel of Omeprazole Magnesium for Oral Drug Delivery System. Asian J. Pharm. Clin. Res. 2021, 14 (9), 44–52. DOI: 10.22159/ajpcr.2021.v14i9.42231
24. Siripruekpong, W.; Praparatana, R.; Issarachot, O.; Wiwattanapatapee, R. Simultaneous Delivery of Curcumin and Resveratrol via In Situ Gelling, Raft-Forming, Gastroretentive Formulations. Pharmaceutics 2024, 16 (5), Art. No: 641. DOI: 10.3390/pharmaceutics16050641
25. Mahmoud, D. B.; Shukr, M. H.; ElMeshad, A. N. Gastroretentive Cosolvent-Based In Situ Gel as a Promising Approach for Simultaneous Extended Delivery and Enhanced Bioavailability of Mitiglinide Calcium. J. Pharm. Sci. 2019, 108 (2), 897–906. DOI: 10.1016/j.xphs.2018.09.020
26. Kathpalia, H.; Salunkhe, S.; Juvekar, S. Formulation of Gastroretentive Sustained Release Floating In Situ Gelling Drug Delivery System of Solubility-Enhanced Curcumin–Soy Lecithin Complex. J. Drug Deliv. Sci. Technol. 2019, 53, Art. No: 101205. DOI: 10.1016/j.jddst.2019.101205
27. Shabaraya, A.; Ashwini, T.; Vineetha, K. Formulation and Evaluation of Gastroretentive In Situ Gelling System of Ketoprofen. Eur. Pharm. J. 2023, 70 (2), 10–19. DOI: 10.2478/afpuc-2023-0018
28. Malviya, V.; Tawar, M.; Burange, P.; Bairagi, R. Preparation and Characterization of Gastroretentive Sustained Release In-Situ Gel of Lafutidine. Int. J. Pharm. Sci. Nanotechnol. 2022, 15 (6), 6216–6228. DOI: 10.37285/ijpsn.2022.15.6.4
29. Amante, C.; Falcone, G.; Aquino, R. P.; Russo, P.; Nicolais, L.; Del Gaudio, P. In Situ Hydrogel Formulation for Advanced Wound Dressing: Influence of Co-Solvents and Functional Excipient on Tailored Alginate–Pectin–Chitosan Blend Gelation Kinetics, Adhesiveness, and Performance. Gels 2024, 10 (1), Art. No: 3. DOI: 10.3390/gels10010003
30. Debnath, S.; Subhashis, D.; et al. Formulation and Evaluation of Controlled Release Gastro-Retentive In Situ Gel for Diltia zem Hydrochloride. Indian J. Pharm. Educ. Res. 2016, 50 (3 Suppl), S254–S265. DOI: 10.5530/ijper.50.3.36
31. Anyanwu, N. Development and Evaluation of In Situ Gelling Gastroretentive Formulations of Meloxicam. Universal J. Pharm. Res. 2017, 2 (3), 11–14. DOI: 10.22270/ujpr.v2i3.R3
32. Kim, J. H.; Song, S. H.; Joo, S. H.; Park, G. H.; Weon, K.-Y. Formulation of a Gastroretentive In Situ Oral Gel Containing Metformin HCl Based on DoE. Pharmaceutics 2022, 14 (9), Art. No: 1777. DOI: 10.3390/pharmaceutics14091777
33. Patel, T.; Desai, S.; Jain, H.; Meshram, D.; Rahevar, K. Formulation and Evaluation of Floating In-Situ Gel of Nicardipine Hydrochloride. J. Drug Deliv. Ther. 2022, 12 (3S), 196–211. DOI: 10.22270/jddt.v12i3-s.5406
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Lucky Vasave, Shivraj Jadhav, Rushikesh Bachhav, Sunil Mahajan, Deepak Sonawane
This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Prospects in Pharmaceutical Sciences copyright is retained by the authors. The journal publishes articles in the Open Access policy, within the CC BY 4.0 licence.
This is a human-readable summary of (and not a substitute for) the license. Disclaimer.
You are free to:
Share — copy and redistribute the material in any medium or format
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
How to Cite
