Polymer-Dependent Performance of Mucoadhesive Chlorhexidine Gels: A Comparative Evaluation of HPMC and Chitosan Formulations Mucoadhesive CHX Gels Using HPMC and Chitosan
Iranian Journal of Pharmaceutical Sciences,
Vol. 22 No. 1 (2026),
26 January 2026
,
Page 31-45
https://doi.org/10.22037/ijps.v22i1.48631
Abstract
Chlorhexidine (CHX) is a widely used antiseptic agent in oral healthcare. However, conventional mouthwash formulations are limited by poor retention time on mucosal surfaces. This study aimed to develop and compare two mucoadhesive CHX 0.2% gels using Hydroxypropyl Methylcellulose (HPMC) and chitosan polymers to improve drug retention and release performance. Two gel formulations were prepared using HPMC and chitosan as the polymeric base. Their physicochemical properties (pH, viscosity, spreadability), rheological behavior, mucoadhesive strength, in vitro drug release, antimicrobial activity against Staphylococcus aureus and Escherichia coli, and six-week stability were evaluated using validated protocols. Drug release kinetics were modeled using Korsmeyer–Peppas and Higuchi equations. Both gels exhibited pseudoplastic rheology and remained stable throughout storage. The HPMC gel had lower viscosity and greater spreadability, resulting in faster drug release. The chitosan gel demonstrated significantly stronger mucoadhesive strength and sustained drug release over 8 hours. Antimicrobial activity was comparable between formulations. No significant changes in pH or viscosity were observed during the stability period. Both polymers are suitable for CHX gel formulation, with HPMC offering ease of application and rapid release, while chitosan provides superior mucoadhesion and prolonged release. These findings support further in vivo evaluation and highlight the potential of polymer-based CHX gels as improved alternatives to traditional mouthwashes in oral infection management.
- Chlorhexidine
- Mucoadhesive gel
- HPMC
- Chitosan
- Oral drug delivery
- Controlled release
How to Cite
References
1. Salari N, Darvishi N, Heydari M, Bokaee S, Darvishi F, Mohammadi M. Global prevalence of cleft palate, cleft lip and cleft palate and lip: A comprehensive systematic review and meta-analysis. J Stomatol Oral Maxillofac Surg [Internet]. 2022 Apr;123(2):110–20. Available from: https://linkinghub.elsevier.com/retrieve/pii/S246878552100118X
2. Poppolo Deus F, Ouanounou A. Chlorhexidine in Dentistry: Pharmacology, Uses, and Adverse Effects. Int Dent J [Internet]. 2022 Jun;72(3):269–77. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0020653922000259
3. Sarembe S, Kiesow A, Pratten J, Webster C. The Impact on Dental Staining Caused by Beverages in Combination with Chlorhexidine Digluconate. Eur J Dent [Internet]. 2022 Oct 23;16(04):911–8. Available from: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0041-1742123
4. Brookes ZLS, McCullough M, Kumar P, McGrath C. Mouthwashes: Implications for Practice. Int Dent J [Internet]. 2023 Nov;73:S98–101. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0020653923004562
5. Wittczak T, Dudek W, Walusiak-Skorupa J, Swierczynska-Machura D, Palczynski C. Chlorhexidine--still an underestimated allergic hazard for health care professionals. Occup Med (Chic Ill) [Internet]. 2013 Jun 1;63(4):301–5. Available from: https://academic.oup.com/occmed/article-lookup/doi/10.1093/occmed/kqt035
6. Rose MA, Garcez T, Savic S, Garvey LH. Chlorhexidine allergy in the perioperative setting: a narrative review. Br J Anaesth [Internet]. 2019 Jul;123(1):e95–103. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0007091219300807
7. Al-Ani E, Martin C, Britland ST, Doudin K, Hill DJ. The effect of the source and the concentration of polymers on the release of chlorhexidine from mucoadhesive buccal tablets. Saudi Pharm J [Internet]. 2019 Sep;27(6):756–66. Available from: https://linkinghub.elsevier.com/retrieve/pii/S131901641930060X
8. Sankar V, Hearnden V, Hull K, Juras DV, Greenberg M, Kerr A, et al. Local drug delivery for oral mucosal diseases: challenges and opportunities. Oral Dis [Internet]. 2011 Apr 8;17(s1):73–84. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1601-0825.2011.01793.x
9. Golshani S, Vatanara A, Amin M. Recent Advances in Oral Mucoadhesive Drug Delivery. J Pharm Pharm Sci [Internet]. 2022 Jun 15;25:201–17. Available from: https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/32705
10. Fini A, Bergamante V, Ceschel GC. Mucoadhesive Gels Designed for the Controlled Release of Chlorhexidine in the Oral Cavity. Pharmaceutics [Internet]. 2011 Sep 27;3(4):665–79. Available from: https://www.mdpi.com/1999-4923/3/4/665
11. Juliano C, Cossu M, Pigozzi P, Rassu G, Giunchedi P. Preparation, In Vitro Characterization and Preliminary In Vivo Evaluation of Buccal Polymeric Films Containing Chlorhexidine. AAPS PharmSciTech [Internet]. 2008 Dec 19;9(4):1153–8. Available from: http://link.springer.com/10.1208/s12249-008-9153-6
12. Richards D. Caries prevention - little evidence for use of chlorhexidine varnishes and gels. Evid Based Dent [Internet]. 2015 Jun 26;16(2):43–4. Available from: https://www.nature.com/articles/6401091
13. Al Haushey L. Study of different factors affecting spreadability and release of ibuprofen from carbopol gels using screening design methodology. ACTA Pharm Sci [Internet]. 2024;62(2):480. Available from: http://www.actapharmsci.com/doi.php?doi=10.23893/1307-2080.APS6230
14. Woertz C, Preis M, Breitkreutz J, Kleinebudde P. Assessment of test methods evaluating mucoadhesive polymers and dosage forms: An overview. Eur J Pharm Biopharm [Internet]. 2013 Nov;85(3):843–53. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0939641113002427
15. Loganathan A, Varghese RM, Subramanian AK, Shanmugam R. Evaluation of Antibacterial Effects of an Oral Rinse Containing Ocimum tenuiflorum and Ocimum gratissimum on Streptococcus mutans and Lactobacillus Species. Cureus [Internet]. 2024 Aug 27; Available from: https://www.cureus.com/articles/282503-evaluation-of-antibacterial-effects-of-an-oral-rinse-containing-ocimum-tenuiflorum-and-ocimum-gratissimum-on-streptococcus-mutans-and-lactobacillus-species
16. Bernkop-Schnürch A. Chitosan and its derivatives: potential excipients for peroral peptide delivery systems. Int J Pharm [Internet]. 2000 Jan;194(1):1–13. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0378517399003658
17. M. Ways T, Lau W, Khutoryanskiy V. Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems. Polymers (Basel) [Internet]. 2018 Mar 5;10(3):267. Available from: https://www.mdpi.com/2073-4360/10/3/267
18. Sogias IA, Khutoryanskiy V V., Williams AC. Exploring the Factors Affecting the Solubility of Chitosan in Water. Macromol Chem Phys [Internet]. 2010 Feb 15;211(4):426–33. Available from: https://onlinelibrary.wiley.com/doi/10.1002/macp.200900385
19. Suriyaamporn P, Sahatsapan N, Patrojanasophon P, Opanasopit P, Kumpugdee-Vollrath M, Ngawhirunpat T. Optimization of In Situ Gel-Forming Chlorhexidine-Encapsulated Polymeric Nanoparticles Using Design of Experiment for Periodontitis. AAPS PharmSciTech [Internet]. 2023 Jul 28;24(6):161. Available from: https://link.springer.com/10.1208/s12249-023-02600-0
20. Ostróżka-Cieślik A, Strasser C, Dolińska B. Insulin-Loaded Chitosan–Cellulose-Derivative Hydrogels: In Vitro Permeation of Hormone through Strat-M® Membrane and Rheological and Textural Analysis. Polymers (Basel) [Internet]. 2024 Sep 16;16(18):2619. Available from: https://www.mdpi.com/2073-4360/16/18/2619
21. Ghica M, Hîrjău M, Lupuleasa D, Dinu-Pîrvu CE. Flow and Thixotropic Parameters for Rheological Characterization of Hydrogels. Molecules [Internet]. 2016 Jun 16;21(6):786. Available from: https://www.mdpi.com/1420-3049/21/6/786
22. Bajwa K, Bishnoi NR, Kirrolia A, Gupta S, Tamil Selvan S. Response surface methodology as a statistical tool for optimization of physio-biochemical cellular components of microalgae Chlorella pyrenoidosa for biodiesel production. Appl Water Sci [Internet]. 2019 Jul 28;9(5):128. Available from: http://link.springer.com/10.1007/s13201-019-0969-x
23. Wojtyłko M, Froelich A, Jadach B. Hypromellose-, Gelatin- and Gellan Gum-Based Gel Films with Chlorhexidine for Potential Application in Oral Inflammatory Diseases. Gels [Internet]. 2024 Apr 15;10(4):265. Available from: https://www.mdpi.com/2310-2861/10/4/265
24. Nafee NA, Ismail FA, Boraie NA, Mortada LM. Mucoadhesive Delivery Systems. I. Evaluation of Mucoadhesive Polymers for Buccal Tablet Formulation. Drug Dev Ind Pharm [Internet]. 2004 Jan 14;30(9):985–93. Available from: http://www.tandfonline.com/doi/full/10.1081/DDC-200037245
25. Biswas R, Mondal S, Ansari MA, Sarkar T, Condiuc IP, Trifas G, et al. Chitosan and Its Derivatives as Nanocarriers for Drug Delivery. Molecules [Internet]. 2025 Mar 13;30(6):1297. Available from: https://www.mdpi.com/1420-3049/30/6/1297
26. GRABOVAC V, GUGGI D, BERNKOPSCHNURCH A. Comparison of the mucoadhesive properties of various polymers. Adv Drug Deliv Rev [Internet]. 2005 Nov 3;57(11):1713–23. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0169409X05001468
27. Popa L, Ghica MV, Popescu R, Irimia T, Dinu-Pîrvu CE. Development and Optimization of Chitosan-Hydroxypropyl Methylcellulose In Situ Gelling Systems for Ophthalmic Delivery of Bupivacaine Hydrochloride. Processes [Internet]. 2021 Sep 22;9(10):1694. Available from: https://www.mdpi.com/2227-9717/9/10/1694
28. Baus-Domínguez M, Aguilera FR, Vivancos-Cuadras F, Ferra-Domingo L, Torres-Lagares D, Gutiérrez-Pérez JL, et al. Mucoadhesive Pharmacology: Latest Clinical Technology in Antiseptic Gels. Gels [Internet]. 2023 Dec 26;10(1):23. Available from: https://www.mdpi.com/2310-2861/10/1/23
29. Sáez-Alcaide L, Molinero-Mourelle P, González-Serrano J, Rubio-Alonso L, Bornstein M, López-Quiles J. Efficacy of a topical gel containing chitosan, chlorhexidine, allantoin and dexpanthenol for pain and inflammation control after third molar surgery: A randomized and placebo-controlled clinical trial. Med Oral Patol Oral y Cir Bucal [Internet]. 2020;e644–51. Available from: http://www.medicinaoral.com/medoralfree01/aop/23661.pdf
30. Al-Ani E, Hill D, Doudin K. Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods. Pharmaceuticals [Internet]. 2021 May 23;14(6):493. Available from: https://www.mdpi.com/1424-8247/14/6/493
31. Madrazo-Jimenez M, Rodriguez-Caballero A, Serrera-Figallo M, Garrido-Serrano R, Gutierrez-Corrales A, Gutierrez-Perez J, et al. The effects of a topical gel containing chitosan, 0,2% chlorhexidine, allantoin and despanthenol on the wound healing process subsequent to impacted lower third molar extraction. Med Oral Patol Oral y Cir Bucal [Internet]. 2016;0–0. Available from: http://www.medicinaoral.com/medoralfree01/aop/21281.
32. Zgoda MM, Kołodziejska J. Effect of rheological parameters on pharmaceutical availability of ketoprofen from hydrogel products made on Carbopol base. Polim Med [Internet]. 2006;36(1):11–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16869544
33. Tuğcu-Demiröz F. Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in Mucoadhesive Gels. Chem Pharm Bull (Tokyo) [Internet]. 2017;65(7):660–7. Available from: https://www.jstage.jst.go.jp/article/cpb/65/7/65_c17-00133/_article
34. dos Santos Carvalho JD, Rabelo RS, Hubinger MD. Thermo-rheological properties of chitosan hydrogels with hydroxypropyl methylcellulose and methylcellulose. Int J Biol Macromol [Internet]. 2022 Jun;209:367–75. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0141813022007334
35. Zgoda MM, Kołodziejska J. Effect of rheological parameters on pharmaceutical availability of ketoprofen from hydrogel products made on Carbopol base. Polim Med [Internet]. 2006;36(1):11–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16869544
36. França E de C, Drummond AF, Teixeira KIR, Oliveira RR, Orlando R, Sinisterra RD, et al. Encapsulated Chlorhexidine Gel Use in Adolescents Undergoing Orthodontic Treatment: A Randomised Trial. Int Dent J [Internet]. 2025 Apr;75(2):1011–20. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0020653924015648
37. Goswami V, Yeltiwar RK, Kujur S, Agrawal P, Bodhi S, Bhatnagar S. Evaluation of Efficacy of Subgingival Administration of 1% Chlorhexidine Gel as an Adjunct to Scaling and Root Planing in the Treatment of Chronic Periodontitis - A Clinical and Microbiological Study. Indian J Dent Res [Internet]. 2022 Apr;33(2):174–9. Available from: https://journals.lww.com/10.4103/ijdr.ijdr_936_21
38. Bonengel S, Bernkop-Schnürch A. Thiomers — From bench to market. J Control Release [Internet]. 2014 Dec;195:120–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0168365914004568.
- Abstract Viewed: 158 times
- IJPS_Volume22_Issue1_Pages31-45 Downloaded: 140 times