Development of 2% w/w sodium fluoride oral gels for prevention of dental caries in patients with xerostomia
DOI:
https://doi.org/10.59796/jcst.V13N2.2023.1743Keywords:
Carbopol 940P, dental caries, oral gel, sodium carboxymethylcellulose, sodium fluoride, stability, xerostomic patientsAbstract
For prevention of dental caries in xerostomic patients, 2% w/w sodium fluoride oral gel is frequently prescribed; however, the product has not been officially approved for clinical use in Thailand. Therefore, this study aimed to develop 2% w/w sodium fluoride oral gels dispensed specifically to patients in Rajavithi Hospital. Both single and combined gel bases were prepared from different gelling agents, including gelatin, xanthan gum, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and Carbopol 940P. They were subsequently characterized according to their physicochemical properties, i.e., clarity, spreadability, pH values, and apparent viscosity. All the gel bases were clear viscous liquids of good spreadability, except the xanthan gum gel bases, which were slightly cloudy. The pH values indicate that the gelatin, xanthan gum, and Carbopol 940P gel bases were acidic, while the cellulose gel bases were neutral. The apparent viscosity ranged from 3 to 11.5 x 105 cPs, depending mainly on type and concentration of the gelling agents. After preparation, the gel bases were then incorporated with 1 M pH 7.4 phosphate buffer solution to the final concentration of 5% w/w. Macroscopic characteristics of the buffered gel bases were generally unchanged, except for the apparent viscosity, which decreased slightly. Sodium fluoride was subsequently added to the selected buffered gel bases. The resulting sodium fluoride gels were neutral and transparent viscous liquids of good spreadability and exhibited good stability against the heating-cooling cycle and accelerated testing. Thus, it is conceivable that 2% w/w sodium fluoride oral gels with acceptable physicochemical characteristics and excellent stability were successfully developed.
References
Agarwal, D., Purohit, B., Ravi, P., Priya, H., & Kumar, V. (2022). Effectiveness of topical fluorides in prevention of radiation caries in adults: A systematic review and meta-analysis. Oral Oncology, 129, Article 105869. https://doi.org/10.1016/j.oraloncology.2022.105869
Ahuja, A., Khar, R. K., & Ali, J. (1997). Mucoadhesive drug delivery systems. Drug Development and Industrial Pharmacy, 23 (5), 489-515. https://doi.org/10.3109/03639049709148498
Amaral, T. N., Junqueira, L. A., Tavares, L. S., Oliveira, N. L., Prado, M. E. T., & de Resende, J. V. (2019). Effects of salts and sucrose on the rheological behavior, thermal stability, and molecular structure of the Pereskia aculeata Miller mucilage. International journal of biological macromolecules, 131, 218-229. https://doi.org/10.1016/j.ijbiomac.2019.03.063
Aslani, A., Zolfaghari, B., & Davoodvandi, F. (2016). Design, formulation, and evaluation of an oral gel from Punica Granatum flower extract for the treatment of recurrent aphthous stomatitis. Advanced Pharmaceutical Bulletin, 6(3), 391-398. https://doi.org/10.15171/apb.2016.051
Bak, J. H., & Yoo, B. (2018). Intrinsic viscosity of binary gum mixtures with xanthan gum and guar gum: Effect of NaCl, sucrose, and pH. International journal of biological macromolecules, 111, 77-81. https://doi.org/10.1016/j.ijbiomac.2017.12.144
Bialik, M., Kuras, M., Sobczak, M., & Oledzka, E. (2021). Achievements in thermosensitive gelling systems for rectal administration. International Journal of Molecular Sciences, 22(11), Article 5500. https://doi.org/10.3390/ijms22115500
Brunchi, C. E., Morariu, S., & Bercea, M. (2021). Impact of ethanol addition on the behaviour of xanthan gum in aqueous media. Food Hydrocolloids, 120, Article 106928. https://doi.org/ 10.1016/j.foodhyd.2021.106928
Budiman, A., Praditasari, A., Rahayu, D., & Aulifa, D.L. (2019). Formulation of antioxidant gel from black mulberry fruit extract (Morus nigra L.). Journal of Pharmacy and Bioallied Sciences, 11, 216-222. https://doi.org/10.4103/jpbs.JPBS_57_18
Cassolato, S. F., & Turnbull, R. S. (2003). Xerostomia: Clinical aspects and treatment. Gerodontology, 20 (2), 64-77. https://doi.org/10.1111/j.1741-2358.2003.00064.x
Daryab, M., Faizi, M., Mahboubi, A., & Aboofazeli, R. (2022). Preparation and characterization of lidocaine-loaded, microemulsion-based topical gels. Iranian Journal of Pharmaceutical Research, 21(1), Article e123787. https://doi.org/10.5812/ijpr.123787
Das, P., Konale, S., & Kothamasu, R. (2014, February). Effect of salt concentration on base-gel viscosity of different polymers used in stimulation fluid systems. In SPE/EAGE European Unconventional Resources Conference and Exhibition (Vol. 2014, No. 1, pp. 1-9). EAGE Publications BV. https://doi.org/10.2118/167786-MS
de Moura, M. R. V., & Moreno, R. B. Z. L. (2019). Concentration, brine salinity and temperature effects on xanthan gum solutions rheology. Applied Rheology, 29(1), 69-79. https://doi.org/10.1515/arh-2019-0007
Devarajan, H., & Somasundaram, S. (2019). Salivary proteins and its effects on dental caries – A review. Drug Invention Today, 11(6), 1406-1411.
Draganoiu, E., Rajabi-Siahboomi, A., & Tiwari, S. (2012). Carbomer. Handbook of Pharmaceutical Excipients (pp. 118-123). London, UK: Pharmaceutical Press.
Dreizen, S., Brown, L. R., Daly, T. E., & Drane, J. B. (1977). Prevention of xerostomia-related dental caries in irradiated cancer patients. Journal of Dental Research, 56(2), 99-104. https://doi.org/10.1177/00220345770560022101
Englander, H. R., & Keyes, P. H. (1966). The prevention of dental caries in the Syrian hamster after repeated topical application of sodium fluoride gels. Journal of the American Dental Association, 73(6), 1342-1347. https://doi.org/10.14219/jada.archive.1966.0369
Fantozzi, P. J., Pampena, E., Di Vanna, D., Pellegrino, E., Corbi, D., Mammucari, S., ... & Villa, A. (2020). Xerostomia, gustatory and olfactory dysfunctions in patients with COVID-19. American journal of otolaryngology, 41(6), Article 102721. https://doi.org/ 10.1016/j.amjoto.2020.102721
Featherstone, J. D. (2000). The science and practice of caries prevention. The Journal of the American dental association, 131(7), 887-899. https://doi.org/10.14219/jada.archive.2000.0307
Hao, Z. Q., Chen, Z. J., Chang, M. C., Meng, J. L., Liu, J. Y., & Feng, C. P. (2018). Rheological properties and gel characteristics of polysaccharides from fruit-bodies of Sparassis crispa. International Journal of Food Properties, 21(1), 2283-2295. https://doi.org/10.1080/10942912.2018.1510838
Hara, A. T., Ando, M., González-Cabezas, C., Cury, J. A., Serra, M. C., & Zero, D. T. (2006). Protective effect of the dental pellicle against erosive challenges in situ. Journal of dental research, 85(7), 612-616. https://doi.org/10.1177/154405910608500706
Hasan, N., Nayak, A. K., Sanaullah, S., Sami, F., Majeed, S., Badgujar, V. B., ... & Ansari, M. T. (2022). Design and evaluation of dental pastes Containing anti-inflammatory drugs. Brazilian Journal of Pharmaceutical Sciences, 58, Article e18655. https://doi.org/10.1590/s2175-97902022e18655
Huang, M., Mao, Y., Li, H., & Yang, H. (2021). Kappa-carrageenan enhances the gelation and structural changes of egg yolk via electrostatic interactions with yolk protein. Food Chemistry, 360, Article 129972. https://doi.org/ 10.1016/j.foodchem.2021.129972
Huang, M., Theng, A. H. P., Yang, D., & Yang, H. (2021). Influence of ĸ-carrageenan on the rheological behavior of a model cake flour system. LWT – Food Science and Technology, 136, 110324. https://doi.org/10.1016/j.lwt.2020.110324
Jaber, S. A., Sulaiman, H. T., & Rajab, N. A. (2020). Preparation, characterization and in-vitro diffusion study of different topical flurbiprofen semisolids. International Journal of Drug Delivery Technology, 10(1), 81-87. https://doi.org/10.25258/ijddt.10.1.12
Jaworski, Z., Spychaj, T., Story, A., & Story, G. (2022). Carbomer microgels as model yield-stress fluids. Reviews in Chemical Engineering, 38(7), 881-919. https://doi.org/10.1515/revce-2020-0016
Jose, T., George, G. B., Baby, M., Aluckal, E., Padiyath, S., Kuruvila, J., & Peter, P. (2018). Xerostomia – An overview. Italian Journal of Dental Medicine, 3(2), 39-42. https://doi.org/10.32033/ijdm.2018.3.02.4
Kapourani, A., Kontogiannopoulos, K. N., Manioudaki, A. E., Poulopoulos, A. K., Tsalikis, L., Assimopoulou, A. N., & Barmpalexis, P. (2022). A review on xerostomia and its various management strategies: the role of advanced polymeric materials in the treatment approaches. Polymers, 14(5), Article 850. https://doi.org/10.3390/polym14050850
Kelly, H. M., Deasy, P. B., Busquet, M., & Torrance, A. A. (2004). Bioadhesive, rheological, lubricant and other aspects of an oral gel formulation intended for the treatment of xerostomia. International journal of pharmaceutics, 278(2), 391-406. https://doi.org/ 10.1016/j.ijpharm.2004.03.022
Kotwal, V., Bhise, K., & Thube, R. (2007). Enhancement of iontophoretic transport of diphenhydramine hydrochloride thermosensitive gel by optimization of pH, polymer concentration, electrode design, and pulse rate. Aaps Pharmscitech, 8(4), 320-325. https://doi.org/10.1208/pt0804120
Kristmundsdóttir, T., Sigurdsson, P., & Thormar, H. (2003). Effect of buffers on the properties of microbicidal hydrogels containing monoglyceride as the active ingredient. Drug development and industrial pharmacy, 29(2), 121-129. https://doi.org/10.1081/DDC-120016719
Kubbi, J. R., Reddy, L. R., Duggi, L. S., & Aitha, H. (2015). Xerostomia: an overview. Journal of Indian Academy of Oral Medicine and Radiology, 27(1), 85-89. https://doi.org/10.4103/0972-1363.167104
Lee, C. H., Moturi, V., & Lee, Y. (2009). Thixotropic property in pharmaceutical formulations. Journal of controlled release, 136(2), 88-98. https://doi.org/10.1016/j.jconrel.2009.02.013
Lucero, M. J., García, J., Vigo, J., & León, M. J. (1995). A rheological study of semisolid preparations of Eudragit®. International journal of pharmaceutics, 116(1), 31-37. https://doi.org/10.1016/0378-5173(94)00268-A
Ma, F., Li, X., Ren, Z., Särkkä-Tirkkonen, M., Zhang, Y., Zhao, D., & Liu, X. (2021). Effects of concentrations, temperature, pH and co-solutes on the rheological properties of mucilage from Dioscorea opposita Thunb. and its antioxidant activity. Food Chemistry, 360, 130022. https://doi.org/10.1016/j.foodchem.2021.130022
Maraie, N. K., & Kadhium, H. S. (2019). Efficacy of Gelling Agents on The In Vitro Release and Physical Properties of Loxoprofen Sodium Gel Containing Ultra Elastic Vesicles. Technology, 9(4), 671-677. https://doi.org/10.25258/ijddt.9.4.26
Moore, T., Croy, S., Mallapragada, S., & Pandit, N. (2000). Experimental investigation and mathematical modeling of Pluronic® F127 gel dissolution: drug release in stirred systems. Journal of Controlled Release, 67(2-3), 191-202. https://doi.org/10.1016/S0168-3659(00)00215-7
Nayak, P. (2020). Topical fluoride for prevention of dental caries: A review. Indian Journal of Forensic Medicine & Toxicology, 14(4), 9120-9123. https://doi.org/10.37506/ijfmt.v14i4.13167
Pankhurst, C. L., Dunne, S. M., & Rogers, J. O. (1996). Restorative dentistry in the patient with dry mouth: Part 2. Problems and solutions. Dental update, 23(3), 110-114.
Patel, J., Maji, B., Moorthy, H. N., & Maiti, S. (2020). Xanthan gum derivatives: review of synthesis, properties and diverse applications. RSC Advances, 10, 27103-27136. https://doi.org/10.1039/d0ra04366d
Pavithra, K., Jeganath, S., & Iqbal, A. (2018). Design, development, and characterization of topical gel containing itraconazole – antifungal agent. Asian Journal of Pharmaceutical and Clinical Research, 11(4), 153-158. http://dx.doi.org/10.22159/ajpcr.2018.v11s4.31725
Podczeck, F. (2012). Gelatin. Handbook of Pharmaceutical Excipients (pp. 319-323). London, UK: Pharmaceutical Press.
Poppe, J. (1997). Gelatin. Thickening and Gelling Agents for Food (pp. 144-168). Dordrecht: Springer-Science+Business Media.
Porter, S. R., Scully, C., & Hegarty, A. M. (2004). An update of the etiology and management of xerostomia. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 97(1), 28-46. https://doi.org/10.1016/j.tripleo.2003.07.010
Rowe, R. C., Sheskey, P. J., Cook, W. G., & Fenton, M. E. (2012). Handbook of Pharmaceutical Excipients. London, UK: Pharmaceutical Press.
Sahlan, M., Prakoso, C. D., Darwita, R. R., & Hermansyah, H. (2017). Formulation of microemulsion propolis fluoride (PF) as varnish topical agent to stop activity of teeth caries. AIP Conference Proceedings, 1817 (1), 030015. https://doi.org/10.1063/1.4976784
Sanjana, A., Ahmed, M. G., & Bh, J. G. (2021). Preparation and evaluation of in-situ gels containing hydrocortisone for the treatment of aphthous ulcer. Journal of Oral Biology and Craniofacial Research, 11(2), 269-276. https://doi.org/10.1016/j.jobcr.2021.02.001
Schiødt, M., Dodd, C. L., Greenspan, D., Daniels, T. E., Chernoff, D., Hollander, H., ... & Greenspan, J. S. (1992). Natural history of HIV-associated salivary gland disease. Oral surgery, oral medicine, oral pathology, 74(3), 326-331. https://doi.org/10.1016/0030-4220(92)90069-3
Seethalakshmi, C., Reddy, R. J., Asifa, N., & Prabhu, S. (2016). Correlation of salivary pH, incidence of dental caries and periodontal status in diabetes mellitus patients: a cross-sectional study. Journal of clinical and diagnostic research: JCDR, 10(3), ZC12-XC14. https://doi.org/10.7860/JCDR/2016/16310.7351
Shah, H. C., & Singh, K. K. (2012). Xanthan gum. Handbook of Pharmaceutical Excipients (pp. 897-900). London, UK: Pharmaceutical Press.
Shao, H., Zhang, H., Tian, Y., Song, Z., Lai, P. F., & Ai, L. (2019). Composition and rheological properties of polysaccharide extracted from tamarind (Tamarindus indica L.) seed. Molecules, 24(7), Article 1218. https://doi.org/ 10.3390/molecules24071218
Su, N., Marek, C. L., Ching, V., & Grushka, M. (2011). Caries prevention for patients with dry mouth. J Can Dent Assoc, 77, Article b85.
The United States Pharmacopeial Convention. (2018). The United States Pharmacopeia. Baltimore MD, USA: United Book Press.
Ullah, R., Zafar, M. S., Al-Munawwarah, A. M., & Arabia, S. (2015). Oral and dental delivery of fluoride: a review. Fluoride, 48(3), 195-204.
Valenta, C., & Auner, B. G. (2004). The use of polymers for dermal and transdermal delivery. European Journal of Pharmaceutics and Biopharmaceutics, 58(2), 279-289. https://doi.org/10.1016/j.ejpb.2004.02.017
Zagorulko, E. Y., & Karavaeva, A. S. (2021). Approaches to the selection of excipients for dental gel with cetylpyridinium chloride. Pharmacy & Pharmacology, 9(1), 54-63. https://doi.org/ 10.19163/2307-9266-2021-9-1-54-63
Zuppolini, S., Salama, A., Cruz-Maya, I., Guarino, V., & Borriello, A. (2022). Cellulose amphiphilic materials: Chemistry, process and applications. Pharmaceutics, 14(2), 386. https://doi.org/ 10.3390/pharmaceutics14020386
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
