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Recent Patents on Drug Delivery & Formulation

Editor-in-Chief

ISSN (Print): 1872-2113
ISSN (Online): 2212-4039

Research Article

Formulation, Development, and Evaluation of Herbal Effervescent Mouthwash Tablet Containing Azadirachta Indica (Neem) and Curcumin for the Maintenance of Oral Hygiene

Author(s): Mankaran Singh, Deepak Sharma*, Dinesh Kumar, Gurmeet Singh, Gaurav Swami and Mahendra Singh Rathore

Volume 14 , Issue 2 , 2020

Page: [145 - 161] Pages: 17

DOI: 10.2174/1872211314666200820142509

Price: $65

Abstract

Background: Dental caries originate due to the localized dissolution of the hard tissues of teeth, mainly caused by acids, developed by the presence of microorganisms in the biofilm (dental plaque) on the surface of teeth causing “cavities”. Commercially available liquid mouthwashes containing synthetic active ingredients possess limitations like teeth staining, higher alcoholic content, taste disturbances, xerostomia, and stability issues.

Objective: To make the solid preparation for oral hygiene (US6428770B1) in the form of herbal effervescent mouthwash tablet (CN106619318A, US8728446B2) using Azadirachta indica and Curcumin having antimicrobial, antibacterial, antiplaque, and anti-inflammatory activity.

Methods: The optimization study of effervescent granules was performed by 33 factorial design. A total of 27 preliminary experimental batches were prepared by the fusion method, varying the amount of citric acid, tartaric acid, and sodium bicarbonate. A complex of curcumin was prepared with hydroxyl propyl β-cyclodextrin and further examined by scanning electron microscopy. The prepared tablets were evaluated for pre and post-compression parameters. The in vitro antimicrobial study was performed by Agar well diffusion method against S. mutans.

Results: All the experimental batches of effervescent granules were evaluated for pH, effervescent time, and CO2 content. Six batches were further selected for final tablet preparation. The results of the pre-compression parameters revealed excellent flow properties and post-compression parameters; the results were also significant. The antimicrobial study revealed the F3 as a final best formulation.

Conclusion: The developed herbal formulation (F3) has a good potential to maintain oral hygiene as compared to alcoholic mouthwash and further studies may be necessary to confirm the efficacy of the formulation since only a single bacterial strain was assayed.

Keywords: Dental caries, oral hygiene, effervescent mouthwash tablet, antimicrobial study, Curcumin, Azadirachta indica.

Graphical Abstract
[1]
Epidemiology, etiology, and prevention of periodontal diseases. Report of a WHO Scientific Group. World Health Organ Tech Rep Ser 1978; (621): 1-60.
[PMID: 100973]
[2]
Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C. The global burden of oral diseases and risks to oral health. Bull World Health Organ 2005; 83(9): 661-9.
[PMID: 16211157]
[3]
Okpalugo J, Ibrahim K, Inyang US. Toothpaste formulation efficacy in reducing oral flora. Trop J Pharm Res 2009; 8(1): 71-7.
[http://dx.doi.org/10.4314/tjpr.v8i1.14714]
[4]
van Tilburg Bernardes E, Lewenza S, Reckseidler-Zenteno S. Current research approaches to target biofilm infections. Postdoc J 2015; 3(6): 36-49.
[PMID: 28748199]
[5]
Kaur RK, Singh MP, Chopra R, Bhatia A. To evaluate the efficacy of three commercially available herbal mouthwashes in treatment of chronic gingivitis: A comparative clinical study. Int J Dent Med Res 2014; 1(4): 42-6.
[6]
Singh S, Anuradha P, Sahana S, Narayan M, Agarwal S. Comparative evaluation of mouth rinsing with plain water and an antibacterial mouth rinse on salivary pH: A randomized clinical trial. J Indian Assoc Public Health Dent 2017; 15(4): 302-5.
[http://dx.doi.org/10.4103/jiaphd.jiaphd_54_17]
[7]
Teki K, Bhat R. Composition Analysis of the oral care products available in indian markets part I mouthwashes. Int J Adv Res Pharm Bio Sci 2012; 2(3): 338-47.
[8]
Hurwitz MM. Oral hygiene tablets and capsules for direct oral delivery of active ingredients US 8728446B2, 2014.
[9]
Ronx X, Shengan T, Jing W, Zhixin X, Linlin C, Qingyao C. Making method of herbal effervescent tablets for rinsing mouth CN106619318A 2017.
[10]
Phatak AA, Patankar RD, Galgatte UC. Antimicrobial activity of a poly-herbal extract against dental micro flora. Res J Pharm Biol Chem Sci 2011; 2(2): 533-9.
[11]
Mosaddek A, Rashid M. A comparative study of the anti-inflammatory effect of aqueous extract of neem leaf and dexamethasone. Bangladesh J Pharmacol 2008; 3(1): 44-7.
[http://dx.doi.org/10.3329/bjp.v3i1.836]
[12]
Chatterjee A, Saluja M, Singh N, Kandwal A. To evaluate the antigingivitis and antipalque effect of an Azadirachta indica (neem) mouthrinse on plaque induced gingivitis: A double-blind, randomized, controlled trial. J Indian Soc Periodontol 2011; 15(4): 398-401.
[http://dx.doi.org/10.4103/0972-124X.92578 ] [PMID: 22368367]
[13]
Packia Lekshmi NCJ, Sowmia N, Viveka S. The inhibiting effect of Azadirachta indica against dental pathogens. Asian J Plant Sci Res 2012; 2(1): 6-10.
[14]
Rahmani AH, Alsahli MA, Aly SM, Khan MA, Aldebasi YH. Role of curcumin in disease prevention and treatment. Adv Biomed Res 2018; 7: 38.
[http://dx.doi.org/10.4103/abr.abr_147_16 ] [PMID: 29629341]
[15]
Hewlings SJ, Kalman DS. Curcumin: A Review of its effects on human health. Foods 2017; 6(10): 92.
[http://dx.doi.org/10.3390/foods6100092 ] [PMID: 29065496]
[16]
Milkvy W, Tucci R. Effervescent mouthwash tablet US3772431A 1973.
[17]
Aslani A, Sharifian T. Formulation, characterization and physicochemical evaluation of amoxicillin effervescent tablets. Adv Biomed Res 2014; 3: 209.
[http://dx.doi.org/10.4103/2277-9175.143252 ] [PMID: 25371866]
[18]
Kayane S, Yano Y, Kiji S, et al. Solid preparation for oral hygiene US6428770B1 2002.
[19]
Fatima F, Katakam P. Design and characterization of nizatidine effervescent floating matrix tablets by employing semisynthetic rate-retarding polymers. Int J Pharm Anal Res 2013; 2(4): 210-20.
[20]
Patel AA, Parikh RH, Sharma OP, Mehta TA. Development and optimization of effervescent tablets of promethazine. Int J Pharm Sci Res 2015; 6(12): 5077-84.
[21]
Jassim ZE, Nawal A, Rajab NA, Mohammed NH. Study the effect of wet granulation and fusion methods on preparation, characterization, and release of Lornoxicam sachet effervescent granules. Drug Invent Today 2018; 10(9): 1612-6.
[22]
Hiola R, Tungadi R. Development of effervescent granule of corn milk, supplemented with probiotics lactobacillus strain shirota. Int J App Pharm 2018; 10(5): 71-5.
[http://dx.doi.org/10.22159/ijap.2018v10i5.27459]
[23]
Pandey P, Sharma P, Gupta R, et al. Formulation and evaluation of herbal effervescent granules incorporated with Martynia Annua extract. J Drug Discov Ther 2013; 1(5): 54-7.
[24]
Amol S, Rakte AS, Nanjwade BK. Development, characterization and preclinical evaluation of some novel enzymes with vitamin. World J Pharm Res 2015; 4(5): 2096-123.
[25]
Jantarat C, Sirathanarun P, Ratanapongsai S. Curcumin-Hydroxypropyl-β-Cyclodextrin inclusion complex preparation methods: effect of common solvent evaporation, freeze drying, and ph shift on solubility and stability of curcumin. Trop J Pharm Res 2014; 13(8): 1215-23.
[http://dx.doi.org/10.4314/tjpr.v13i8.4]
[26]
Aslani A, Jahangiri H. Formulation, characterization and physicochemical evaluation of ranitidine effervescent tablets. Adv Pharm Bull 2013; 3(2): 315-22.
[PMID: 24312854]
[27]
Rockville MD. United States of Pharmacopeia-National Formulary. The United States Pharmacopoeial Convention.
[28]
Abdoun S, Hassan TI, Gaber DA, El-Sharekh A. Antidepressant activity of A. hierochuntica L. effervescent granules using forced swimming test. J Innov Pharm Biol Sci 2019; 6(2): 38-44.
[29]
Derle D, Khandekar S, Bhavsar A, Derle N. Formulation development and evaluation of effervescent tablet of Paracetamol and n-acetylcysteine. Indo Amer J Pharm Res 2017; 7(3): 7946-54.
[30]
Al-mousawy J, Al-hussainy Z, Alaayedi M. Formulation and evaluation of effervescent granules of ibuprofen. Int J Appl Pharm 2019; 11(6): 66-9.
[http://dx.doi.org/10.22159/ijap.2019v11i6.34912]
[31]
Firodiya SR, Gaikwad MS, Bairagi SM, Kharat SS, Mote GD. Formulation and evaluation of effervescent tablet of Valsartan. Int J Pharm Drug Anal 2017; 5(4): 136-43.
[32]
Sayani Bhattacharyya S, Swetha G. Formulation and evaluation of effervescent granules of Fexofenadine hydrochloride. Pharm Innov J 2014; 3(3): 1-8.
[33]
Indian Pharmacopoeia. Government of India and Ministry of Health and Family Welfare. 6th ed. Ghaziabad: Published by The Indian Pharmacopoeia Commission 2010; Vol. I & II.
[34]
Singh S, Virmani T, Virmani R, Kumar P, Mahlawat G. Fast dissolving drug delivery systems: formulation, preparation techniques and evaluation. Univ J Pharm Res 2018; 3(4): 60-9.
[http://dx.doi.org/10.22270/ujpr.v3i4.185]
[35]
Khan SI, Navya B. Kumar. Formulation, optimization and evaluation of Caffeine effervescent tablets. Indo Amer J Pharm Sci 2018; 5(4): 2222-9.
[36]
Khedekar SL, Deshmane SV. Formulation, development and evaluation of mouth dissolving tablet containing cyclodextrin as taste masker. IOSR J Pharm 2019; 9(1): 21-9.
[37]
Rahim SA, Carter PA, Elkordy AA. Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug. Drug Des Devel Ther 2015; 9: 1843-57.
[PMID: 25848220]
[38]
Diyya ASM, Thomas NV. Formulation and evaluation of metronidazole effervescent granules. Int J Pharm Sci Res 2018; 9(6): 2525-9.
[39]
Elkhodairy KA, Hassan MA, Afifi SA. Formulation and optimization of orodispersible tablets of flutamide. Saudi Pharm J 2014; 22(1): 53-61.
[http://dx.doi.org/10.1016/j.jsps.2013.01.009 ] [PMID: 24493974]
[40]
Hussain HAM, Al-Khedairy EBH. Preparation and in vitro evaluation of cyclodextrin based effervescent and dispersible granules of carbamazepine. Int J Appl Pharm 2018; 10(6): 290-7.
[http://dx.doi.org/10.22159/ijap.2018v10i6.28276]
[41]
Sharma D, Kaur P, Singh G, Singh D, Verma S, Singh J. Development and validation of stability indicating UV visible spectrophotometric method for simultaneous estimation of Neem (Azadirachtin) and Curcumin in pharmaceutical tablet dosage form. Anal Chem Lett 2019; 9(4): 564-81.
[http://dx.doi.org/10.1080/22297928.2019.1652113]
[42]
Senthilkumaran R, Pavithra E. In-vitro sensitivity of bacterial and fungal pathogens to Datura alba – An antimicrobial approaches. Int J Adv Res Biol Sci 2014; 1(1): 101-10.
[43]
Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. J Pharm Anal 2016; 6(2): 71-9.
[http://dx.doi.org/10.1016/j.jpha.2015.11.005 ] [PMID: 29403965]
[44]
Saif MMS, Al-Fakih AA, Hassan MAM. Antibacterial activity of selected plant (Aqueous and methanolic) extracts against some pathogenic bacteria. J Pharmacog Phytochem 2017; 6(6): 1929-35.
[45]
Chuong CM, Kelley CJ, Muhammad Y. Investigating effect of water of hydration on active pharmaceutical ingredients in a water-sensitive dosage form. J Anal Sci Technol 2018; 9: 7.
[http://dx.doi.org/10.1186/s40543-018-0135-3]
[46]
Nair SS. UV-Visible and FTIR Spectroscopic studies of fine powders of Azadirachta indica leaves. Int J Adv Res Sci Engin 2017; 6(3): 242-5.
[47]
Nair DL, Sar KS, Arora A, Mahapatra D. Fourier transform infrared spectroscopy analysis of few medicinal plants of Chhattisgarh, India. J Adv Phar. Educ Res 2013; 3(3): 196-200.
[48]
Athira GK, Jyothi AN. Preparation and characterization of curcumin loaded cassava starch nanoparticles with improved cellular absorption. Int J Pharm Pharm Sci 2014; 6(10): 171-6.
[49]
Hu L, Shi Y, Li JH. Enhancement of oral bioavailability of Curcumin by a novel solid dispersion system. AAPS PharmSciTech 2015; 16(6): 1327-34.
[http://dx.doi.org/10.1208/s12249-014-0254-0 ] [PMID: 25804949]
[50]
Shaik R, Reddy SP, Shaik S, Nemalladinne SES, Reddy DSP, Praveen KNS. Estimation of pH, total acid and ethanol content of commercially available alcohol-containing mouthwashes and its effect on salivary pH. J Evid Based Med Healthc 2017; 4(54): 3302-7.
[http://dx.doi.org/10.18410/jebmh/2017/656]
[51]
Singh B, Saini G, Vyas M, Verma S, Thakur S. Optimized chronomodulated dual release bilayer tablets of fexofenadine and montelukast: quality by design, development, and in vitro evaluation. Future J Pharm Sci 2019; 5: 5.
[http://dx.doi.org/10.1186/s43094-019-0006-9]
[52]
Malisetty SP, Allena RT, Sandina S, Gangadharappa HV. Formulation and evaluation of modified-release effervescent floating tablets of ofloxacin. Int J Health Allied Sci 2013; 2(2): 99-107.
[http://dx.doi.org/10.4103/2278-344X.115685]
[53]
Murdiana HE, Revika E, Rahmawati D, Puspitasari TR, Putri AD, Murti BT. Moringa oleifera Lam.-based effervescent tablets: design, formulation and physicochemical evaluation. Int J Drug Deliv Technol 2018; 8(4): 222-8.
[54]
Herlina Kuswardhani N. Belgis M, Tiara A. Characterization of physical and chemical properties of effervescent tablets temulawak (curcuma zanthorrhiza) in the various proportion of sodium bicarbonate and tartaric acid E3S Web of Conferences 2020; 142: 03006.
[55]
Taymouri S, Mostafavi A, Javanmardi M. Formulation and optimization of effervescent tablet containing bismuth sub-citrate. J Rep Pharm Sci 2019; 8(2): 236-44.
[http://dx.doi.org/10.4103/jrptps.JRPTPS_11_19]
[56]
Aslani A, Fattahi F. Formulation, characterization and physicochemical evaluation of potassium citrate effervescent tablets. Adv Pharm Bull 2013; 3(1): 217-25.
[PMID: 24312839]
[57]
Sun H, Wang X, Wang J, Shi G, Chen L. Influence of the formula on the properties of a fast dispersible fruit tablet made from mango, Chlorella, and cactus powder. Food Sci Nutr 2019; 8(1): 479-88.
[http://dx.doi.org/10.1002/fsn3.1330 ] [PMID: 31993172]
[58]
Aslani A, Beigi M. Design, formulation, and physicochemical evaluation of montelukast orally disintegrating tablet. Int J Prev Med 2016; 7(1): 120.
[http://dx.doi.org/10.4103/2008-7802.193097 ] [PMID: 27857833]
[59]
Almanza‐Aranda KE, Aranda‐Fonseca M, Velazquez‐Plascencia G, Garcia‐Contreras R, Part II. Studies of Plants used in Dental Disease. Cytotoxic and Anti-Inflammatory effect of Turmeric and Aloe Vera in a gingivitis model. Scrivener Publishing 2020; LLC: 97-109.
[60]
Mandrol PS, Bhat K, Prabhakar AR. An in vitro evaluation of cytotoxicity of curcumin against human dental pulp fibroblasts. J Indian Soc Pedod Prev Dent 2016; 34(3): 269-72.
[http://dx.doi.org/10.4103/0970-4388.186757 ] [PMID: 27461812]
[61]
Verma UP, Gupta A, Yadav RK, Tiwari R, Sharma R, Balapure AK. Cytotoxicity of chlorhexidine and neem extract on cultured human gingival fibroblasts through fluorescence-activated cell sorting analysis: An in-vitro study. Eur J Dent 2018; 12(3): 344-9.
[http://dx.doi.org/10.4103/ejd.ejd_149_17 ] [PMID: 30147397]
[62]
Verma UP, Dixit J. Development of a human gingival fibroblast (HGF) cell line for the evaluation of a novel mouthwash from Azadirachta Indica vis-à-vis Chlorhexidine. Int J Pharm Pharm Sci 2012; 4(2): 217-21.
[63]
Sharma D, Singh G, Kumar D, Singh M. Formulation development and evaluation of fast disintegrating tablets of salbutamol sulphate, cetirizine hydrochloride in combined pharmaceutical dosage form: a new era in novel drug delivery for pediatrics and geriatrics. J Drug Deliv 2015.2015640529
[http://dx.doi.org/10.1155/2015/640529 ] [PMID: 25810924]

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