FORMULATION AND EVALUATION OF AN ANTIMICROBIAL MUCOADHESIVE DENTAL GEL OF AZADIRACHTA INDICA AND GLYCYRRHIZA GLABRA
Keywords:Azadirachta indica, Glycyrrhiza glabra, Oral local drug delivery, Mucoadhesive gel, Carbopol 934
Objective: Objective of this study was to formulate and evaluate an antimicrobial mucoadhesive dental gel of herbal drugs for the prevention and treatment of dental plaque, dental caries, and periodontitis.
Methods: Azadirachta indica leaves extract was prepared with ethanol: water (80:20 v/v) and Glycyrrhiza glabra roots extract was prepared with ethanol: water (30:70 v/v). Both the extracts were evaluated for organoleptic properties, pH, phytochemical screening and total phenolic content. Thin layer chromatography (TLC) and Reverse-phase high-performance liquid chromatography (RP-HPLC) studies were performed. Antibacterial activity of the extract was done on Mueller Hinton agar media against Streptococcus mutans using the disc diffusion method. A mucoadhesive gel was prepared using carbopol 934, polyethylene glycol (PEG) 400 as a bioadhesive polymer and penetration enhancer, respectively. Three gel formulations were prepared at various concentrations of carbopol 934. Dental gel formulations were evaluated for different parameters such as appearance, pH, viscosity, spreadabilty, syringeability. Optimised batch was used for further studies viz. stability study, drug content, diffusion study to determine percent cumulative release of drug from gel formulation and in vitro mucoadhesion study.
Results: Rf value of nimbin and glycyrrhizin in TLC study, were found to be 0.08 and 0.56, respectively. RP-HPLC method was developed for estimation of active constituents present in both extracts using mobile phase acetonitrile: water [containing 0.1 % v/v glacial Acetic acid (GAA)]: methanol in the ratio of 30:60:10 at the flow rate of 0.8 ml/min. Rt of active constituents from both drug extracts was found to be 3.119 and 4.15 min, respectively. 2.5 % w/v of Azadirachta indica leaves extract showed a good zone of inhibition (10.66±0.577 mm) near to chlorhexidine (11.33±0.5773 mm). 1 % of Glycyrrhiza glabra roots extract exhibit antibacterial activity (9±1 mm) and masks the bitter taste of formulation. Batch (F2) was selected on the basis of viscosity, spreadabilty and syringeability. The optimised batch was found to be stable and has 83 % and 80.3 % of drug content. Percent cumulative releases of the drug from gel formulation during the diffusion study were found to be 87.52 % and 85.43 %. Adhesive force and adhesiveness were found to be 11.90 g and 0.92 millijoule, respectively during mucoadhesion study.
Conclusion: The evaluation parameters of optimized batch indicate the prepared dental gel is mucoadhesive, stable, good delivery drug system containing antimicrobial agents for prevention of plaque formation, dental caries and periodontitis.
World Health Organization (WHO). Dental diseases and oral health Geneva WHO; 2003. Available from: http:// www.who.int/oral_health/publications/en/orh_fact_sheet.pdf. [Last accessed on 02 Jan 2018]
Microbial disease of mouth and oral cavity. Available from: https://courses.lumenlearning.com/microbiology/chapter/microbial-diseases-of-the-mouth-and-oral-cavity/ [Last accessed 10 Jan 2018]
Jain N, Jain GK, Javed S, Iqbal Z, Talegaonkar S, Ahmad FJ, et al. Recent approaches for the treatment of periodontitis. Drug Discovery Today 2008;13:932-43.
Alshahrani I, Tikare S, Meer Z, Mustafa A, Abdulwahab M, Sadatullah S, et al. Prevalence of dental caries among male students aged 15–17 y in southern Asir, Saudi Arabia. Saudi Dent J 2018. Doi:10.1016/j.sdentj.2018.03.003
Nguyen S, Hiorth M. Advanced drug delivery systems for local treatment of the oral cavity. Ther Delivery 2015;6:595-608.
Tariq M, Iqbal Z, Ali J, Baboota S, Talegaonkar S, Ahmad Z, et al. Treatment modalities and evaluation models for periodontitis. Int J Pharma Investig 2012;2:106-22.
Ananthathavam K, Ramamurthy J. Treating periodontitis with the use of essential oil and herbs. IOSRPHR 2014;4:39-42.
Lakshmi T, Krishnan V, Rajendran R, Madhusudhanan N. Azadirachta indica: a herbal panacea in dentistry-an update. Pharmacogn Rev 2015;9:41-4.
Carocho M, Morales P, Ferreira IC. Sweeteners as food additives in the XXI century: a review of what is known, and what is to come. Food Chem Toxicol 2017;107:302-17.
Mathew AK. Oral local drug delivery: an overview. Pharm Pharmacol Res 2015;3:1-6.
Pai MR, Acharya LD, Udupa N. Evaluation of antiplaque activity of Azadirachta indica leaf extract gel-a 6-week clinical study. J Ethnopharmacol 2004;90:99-103.
Alzohairy MA. Therapeutic role of Azadirachta indica (Neem) and their active constituents in disease prevention and treatment. Evid Based Complementary Altern Med 2016;1-11. http://dx.doi.org/10.1155/2016/7382506
Tian M, Yan H, Row KH. Extraction of glycyrrhizic acid and glabridin from licorice. Int J Mol Sci 2008;9:571-7.
Al-Hashemi ZS, Hossain MA. Biological activities of different neem leaf crude extracts used locally in Ayurvedic medicine. Pac Sci Rev A: Nat Sci Eng 2016;18:128-31.
Al-Jadidi HS, Hossain MA. Studies on total phenolic, total flavonoids and antimicrobial activity from the leaves crude extracts of neem traditionally used for the treatment of cough and nausea. Beni-Suef Univ J Basic Appl Sci 2015;4:93-8.
Orujei Y, Shabani L, Sharifi-Tehrani M. Induction of glycyrrhizin and total phenolic compound production in licorice by using arbuscular mycorrhizal fungi. Russ J Plant Physiol 2013;60:855–60.
Kokate CK, Purohit AP, Gokhale SB. Pharmacognosy. 37th ed. Pune: Nirali prakashan; 2015. p. 116.
Vani MM, Rao PSS, Varma GN, Pushpitha K, Biswal L. Identification and chemical characterization of Azadirachta indica leaf extracts through thin layer chromatography. Int J Res Eng Technol 2016;5:117-22.
Senegar NP, Agrawal R, Singh A. A textbook of pharmacognosy. 2nd ed. Hyderabad: Pharma book syndicate; 2009. p. 152-3.
Shaikh S, Jain V. Development and validation of a RP-HPLC method for the simultaneous determination of quercetin, ellagic acid and rutin in hydroalcoholic extract of triphala churna. Int J Appl Pharm 2018;10:169-74.
Jain HK, Nikam VK. Formulation development and stability indicating HPLC assay of tablets of apixaban. Int J Pharm Pharm Sci 2017;9:24-32.
Ranjale AR, Jain HK. Development and validation of RP-HPLC method for simultaneous estimation of cefoperazone and tazobactam in the marketed formulation. Int J Pharm Pharm Sci 2014;6:462-5.
Mueller Hinton agar media. Available from: http://himedialabs.com/TD/M173.pdf [Last accessed 03 Feb 2018]
Maragathavalli S, Brindha S, Kaviyarasi NS, Annadurai B, Gangwar SK. Antimicrobial activity in leaf extract of neem (Azadirachta indica Linn.). Int J Sci Nat 2012;3:110-3.
https://www.uofmhealth.org/health-library/hn-4372000. [Last accessed on 12 Feb 2018]
Sharma M, Dwivedi AK. Nutrition neutraceuticals: a proactive approach for healthcare. Nanotechnol Agri-Food Ind 2016;4:79-116.
Sawan MS. Review on taste masking approaches in oral pharmaceutical dosage forms. Leb Med J 2016;1:33-43.
Fini A, Bergamante V, Ceschel GC. Mucoadhesive gel designed for the controlled release of chlorhexidine in the oral cavity. Pharmaceutics 2011;3:665-79.
Pawar VA, Bhagat TB, Toshniwal MR, Mokashi ND, Khandelwal KR. Formulation and evaluation of dental gel containing essential oil of coriander against oral pathogens. Int Res J Pharm 2013;4:48-54.
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;2:1-9.
Helal DA, El-Rhman DA, Abdel-Halim SA, El-Nabarawi MA. Formulation and evaluation of fluconazole topical gel. Int J Pharm Pharm Sci 2012;4 Suppl 5:176-83.
Bisht N, Goswami L, Kothiyal P. Preparation and evaluation of in-situ oral topical gel of levofloxacin by using a combination of polymers. IJOD 2014;2:142-51.
Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci 1998;1:15-30.
Bansal K, Rawat MK, Jain A, Rajput A, Chaturvedi TP, Singh S, et al. Development of satranidazole mucoadhesive gel for the treatment of periodontitis. AAPS Pharm Sci Tech 2009;10:716-23.
Sabry SA. Sodium cromoglycate mucoadhesive buccal patches: Design, fabrication, in vitro and in vivo characterization. Int J Appl Pharm 2018;10:76-82.
Moldovan M, Lahmar A, Bogdan C, Parauan S, Tomuta I, Crisan M, et al. Formulation and evaluation of a water-in-oil cream containing herbal active ingredients and ferulic acid. Clujul Med 2017;90:212.37.
Gel. https://www.brookfieldengineering.com/applications/texture-applications/personal-care-products/hair-gel. [Last accessed on 20 Feb 2018]
Ghosh A, Chakrabarti P, Roy P, Bhadury S, Nag T, Sarkar S, et al. Bioremediation of heavy metals from neem (Azadirachta indica) leaf extract by chelation with dithizone. Asian J Pharm Clin Res 2009;2:87-92.
Kannusamy G, Rengaswamy G. Phytochemical constituent and in vitro antibacterial activity of the various extract of Azadirachta indica (Neem). Int J Curr Pharm Res 2016;8:52-5.