Formulation and in-vitro characterization of herbal licorice gel for periodontal therapy

Year 2022, Volume: 26 Issue: 4, 1037 - 1051, 28.06.2025

Safiya Fatima Khan Bhavya Shetty Asim Mustafa Khan Ibrahim Fazal

https://izlik.org/JA65XU46ZP

Abstract

Periodontal diseases are inflammations of the periodontium caused by certain microorganisms, leading to progressive
destruction of the periodontal ligament and alveolar bone. Conventional medications have limitations such as
extrinsic tooth discoloration, altered taste sensation, and the development of bacterial resistance. Licorice is an herb
with glycyrrhetinic acid (GA) as its main active component. GA has antimicrobial, anti-inflammatory and antioxidant
activity. There is limited evidence for the preparation and in vitro evaluation of licorice extract as a topical drug in
periodontology. The aim of this study was the formulation and in vitro characterization of a controlled-release gel
containing licorice extract that can be used as a topical agent in periodontal therapy. An in vitro study was conducted
in which an ethanolic extract of licorice was prepared. The local drug delivery gel was formulated with the specified
minimum inhibitory concentration of Glycyrrhiza glabra using Carbopol 940 polymer. In vitro characterization of the
formulated gel was done in terms of physical appearance, determination of pH, squirtability, drug content, gelation
temperature and time, viscosity, mucoadhesive force, in vitro drug release, thermodynamic stability and X-ray
diffraction analysis. The licorice gel formulation was thermodynamically stable, mucoadhesive, and sprayable. It also
released the drug slowly for up to 48 hours. The incorporation of licorice extract into a polymeric gel base exhibits
good physicochemical properties, adequate mucoadhesiveness, and controlled drug release. Thus, it is a potential
herbal extract for local drug delivery that can be used to improve the therapeutic results of scaling and root planning.

Keywords

Periodontal disease , Local Drug Delivery , licorice , herbal extracts

References

• [1] O'Brien‐Simpson NM, Veith PD, Dashper SG, Reynolds EC. Antigens of bacteria associated with periodontitis. Perio 2000. 2004; 35(1): 101-134. [CrossRef]
• [2] Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. The Lancet. 2005; 366(9499): 1809-1820. [CrossRef]
• [3] Feng Z, Weinberg A. Role of bacteria in health and disease of periodontal tissues. Perio 2000. 2006; 40(1): 50-76. [CrossRef]
• [4] Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010; 89(12): 1349-1363. [CrossRef]
• [5] Tonetti MS, Cortellini P. Local drug delivery for the treatment of periodontitis. In: Lang NP, Lindhe J, eds. Clinical periodontology and implant dentistry. 6th edition. John Wiley & Sons, UK, 2015, pp. 891-898.
• [6] Nair SC, Anoop KR. Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery. J Adv Pharm Technol Res. 2012; 3(1): 9–15. [CrossRef] [7] Goodson J. Pharmacokinetic principles controlling efficacy of oral therapy. J Dent Res. 1989; 68: 1625–1632.
• [8] Bukka R, Prakasam K, Patel CD. Preparation and evaluation of intraoral drug delivery system for rasagiline mesylate. Int J Pharm Sci Drug Res. 2010; 2(4): 294-301.
• [9] Position paper The role of controlled drug delivery for periodontitis. J Periodontol. 2000; 71: 125–140. [CrossRef] [10] Van Strydonck DA, Slot DE, Van der Velden U, Van der Weijden F. Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review. J Clin Periodontol. 2012; 39(11): 1042-1055. [CrossRef]
• [11] Bhat N, Mitra R, Reddy JJ, Oza S, Vinayak K. Evaluation of efficacy of chlorhexidine and a herbal mouthwash on dental plaque: An in vitro comparative study. Int J Pharma Bio Sci 2013; 4(3): 625-632. [CrossRef]
• [12] Takamori A, Yoshinaga Y, Ukai T, Nakamura H, Takamori Y, Izumi S, Shiraishi C, Hara Y. Topical application of glycyrrhetinic acid in the gingival sulcus inhibits attachment loss in lipopolysaccharide‐induced experimental periodontitis in rats. J Periodontal Res. 2018; 53(3): 422-429. [CrossRef]
• [13] Long DR, Mead J, Hendricks JM, Hardy ME, Voyich JM. 18β-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression. Antimicrob Agents Chemother. 2013; 57(1): 241-247. [CrossRef]
• [14] Yeh CF, Wang KC, Chiang LC, Shieh DE, Yen MH, San Chang J. Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol. 2013; 148(2): 466- 473. [CrossRef]
• [15] Chandrasekaran CV, Deepak HB, Thiyagarajan P, Kathiresan S, Sangli GK, Deepak M, Agarwal A. Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products. Phytomedicine. 2011; 18(4): 278-84. [CrossRef] [16] Li S, Zhu JH, Cao LP, Sun Q, Liu HD, Li JS, Hang CH. Growth inhibitory in vitro effects of glycyrrhizic acid in U251 glioblastoma cell line. Neurol Sci. 2014; 35(7): 1115-1120. [CrossRef] [17] Sharifzadeh M, Shamsa F, Shiran S, Karimfar MH, Miri AH, Jalalizadeh H, Gholizadeh S, Salar F, Tabrizian K. A time course analysis of systemic administration of aqueous licorice extract on spatial memory retention in rats. Planta Med. 2008; 74(05): 485-490. [CrossRef]
• [18] Michel HE, Tadros MG, Abdel-Naim AB, Khalifa AE. Prepulse inhibition (PPI) disrupting effects of Glycyrrhiza glabra extract in mice: a possible role of monoamines. Neurosci Lett. 2013; 544: 110-114. [CrossRef] [19] Maksoud HA, Abdel Magid A, Mostafa YM, Elharrif M, Mohamed SR. Ameliorative effect of liquorice extract versus silymarin in experimentally induced chronic hepatitis: a biochemical and genetical study. Clin Nutr Exp. 2019; 23: 69–79. [CrossRef] [20] Messier C, Epifano F, Genovese S, Grenier D. Licorice and its potential beneficial effects in common oro‐dental diseases. Oral Dis. 2012; 18(1): 32-39. [CrossRef] [21] Madan S, Kashyap S, Mathur G. Glycyrrhiza glabra: An efficient medicinal plant for control of periodontitis–A randomized clinical trial. J Int Clin Dent Res Organ. 2019; 11(1): 32-35. [CrossRef]
• [22] Andrews JM. Determination of minimum inhibitory concentrations. J Antimicrob Chemother. 2001; 48(1):5-16. [CrossRef]
• [23] Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B. 2015; 5(4): 310-315. [CrossRef]
• [24] Salari MH, Kadkhoda Z. In vitro antibacterial effects of glycyrrhetinic acid on periodontopathogenic and capnophilic bacteria isolated from adult periodontitis. Clin Microbiol Infect. 2003; 9(9): 987-988. [CrossRef]
• [25] Suttipalin Suwannakul, Plykaeow Chaibenjawong. Antibacterial activities of Glycyrrhiza glabra Linn. (Licorice) root extract against Porphyromonas gingivalis and its inhibitory effects. J Dent Indones. 2017, 24(3): 85-92. [CrossRef]
• [26] Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR. Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. J Control Release. 2000; 67(2-3): 357-368. [CrossRef]
• [27] Jelvehgari M, Rashidi MR, Samadi H. Mucoadhesive and drug release properties of benzocaine gel. Iran J Pharm Sci. 2006; 2(4): 185-194
• [28] Forscher BK, Paulsen AG, Hess WC. The pH of the periodontal pocket and the glycogen content of the adjacent tissue. J Dent Res. 1954; 33(4): 444-453. [CrossRef]
• [29] BM Shivprasad, C Sonali, S Navnita, S Shilpa, KN Sruthi, Savita S., Liquorice as an adjunct to scaling and root planing in the treatment of chronic periodontitis: a clinico-microbiological study. Int J Sci Res. 2017; 6(7): 73-76. [CrossRef]
• [30] Bodet C, La VD, Gafner S, Bergeron C, Grenier D. A licorice extract reduces lipopolysaccharide‐induced proinflammatory cytokine secretion by macrophages and whole blood. J Periodontol. 2008; 79(9): 1752-1761. [CrossRef]
• [31] La VD, Tanabe SI, Bergeron C, Gafner S, Grenier D. Modulation of matrix metalloproteinase and cytokine production by licorice isolates licoricidin and licorisoflavan A: potential therapeutic approach for periodontitis. J Periodontol. 2011; 82(1): 122-128. [CrossRef]
• [32] Kim SR, Jeon HJ, Park HJ, Kim MK, Choi WS, Jang HO, Bae SK. Glycyrrhetinic acid inhibits Porphyromonas gingivalis lipopolysaccharide-induced vascular permeability via the suppression of interleukin-8. Inflamm Res. 2013; 62(2): 145-154. [CrossRef]
• [33] Farhad SZ, Aminzadeh A, Mafi M, Barekatain M. The effect of adjunctive low-dose doxycycline and licorice therapy on gingival crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis. Dent Res J. 2013; 10(5): 624-629.
• [34] Kim HS, Suh KS, Sul D, Kim BJ, Lee SK, Jung WW. The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264. 7 cells. Int J Mol Med. 2012; 29(2): 169-177. [CrossRef]
• [35] Aslani A, Ghannadi A, Najafi H. Design, formulation and evaluation of a mucoadhesive gel from Quercus brantii L. and coriandrum sativum L. as periodontal drug delivery. Adv Biomed Res. 2013; 2(2): 1-9. [CrossRef]
• [36] Saleem MA, Bala S, Liyakat AA. Effect of different carriers on in vitro permeation of meloxicam through rat skin. Indian J Pharm Sci. 2010; 72(6): 710-718. [CrossRef]
• [37] Schwach-Abdellaoui K, Vivien-Castioni N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm. 2000; 50(1): 83-99. [CrossRef]
• [38] Bansal M, Mittal N, Yadav SK, Khan G, Gupta P, Mishra B, Nath G. Periodontal thermoresponsive, mucoadhesive dual antimicrobial loaded in-situ gel for the treatment of periodontal disease: Preparation, in-vitro characterization and antimicrobial study. J Oral Biol Craniofac Res. 2018; 8(2): 126-133. [CrossRef]
• [39] Baloglu E, Karavana SY, Hyusein IY, Kose T. Design and formulation of mebeverine HCl semisolid formulations for intraorally administration. AAPS PharmSciTech. 2010; 11: 181–188. [CrossRef]
• [40] Aslani A, Emami S, Ghannadi A, Ajdari M. Formulation and physicochemical evaluation of an herbal antihemorrohid ointment from Quercus, Black cumin and Fenugreek for the treatment of internal anal hemorrhoids. Pharm Sci Tabriz University of Medical Sciences. 2009; 1(14): 247-257.
• [41] Mukherjee D, Azamthulla M, Santhosh S, Dath G, Ghosh A, Natholia R, Anbu J, Teja BV, Muzammil KM. Development and characterization of chitosan-based hydrogels as wound dressing materials. J Drug Deliv Sci Technol. 2018; 46: 498-510. [CrossRef]
• [42] Yadav SK, Mishra S, Mishra B. Eudragit-based nanosuspension of poorly water- soluble drug: formulation and in-vitro–in vivo evaluation. AAPS PharmSciTech. 2012;13:1031–1044. [CrossRef]
• [43] Tabassum H, Ahmad IZ. Evaluation of the anticancer activity of sprout extract-loaded nanoemulsion of N. sativa against hepatocellular carcinoma. J Microencapsul. 2018; 35(7-8): 643-656. [CrossRef]
• [44] Santhosh S, Mukherjee D, Anbu J, Murahari M, Teja BV. Improved treatment efficacy of risedronate functionalized chitosan nanoparticles in osteoporosis: formulation development, in vivo and molecular modelling studies. J Microencapsul. 2019; 36(4): 338-355. [CrossRef]
• [45] Epp J, X-ray diffraction (XRD) techniques for materials characterization. InMaterials characterization using nondestructive evaluation (NDE) methods, pp.81-124, Woodhead Publishing, 2016. [CrossRef]