Preparation and in-vitro Evaluation of Secnidazole as Periodontal In-situ Gel for Treatment of Periodontal Disease
DOI:
https://doi.org/10.31351/vol31iss2pp50-61Keywords:
Dental in-situ gel, Secnidazole, poloxamerAbstract
This study aims to develop a thermosensitive mucoadhesive periodontal in situ gel of secnidazole for local release of drug for treatment of periodontitis, in order to increase the drug residence time and to increase patient compliance while lowering the side effects of the drug.
Cold method was used to prepare 30 formulas of secnidazole periodontal in situ gel, using different concentrations of thermosensitive polymers (poloxamer407 alone or in combination with poloxamer 188) and methyl cellulose (MC ) or hydroxypropyl methylcellulose (HPMC K4M )in different concentrations used as mucoadhesive polymer and the resultant formulations were subjected to several tests such as gelation temperature GT, appearance and pH value. The formulas with the most appropriate GT were subjected to in-vitro drug release. Three formulas were chosen with appropriate release, F6 (15% P407, 1% MC), F29 (18%P407,3% P188, 0.8% HPMC) and F30 (18%P407,3% P188, 1% HPMC). These formulas were subjected to mucoadhesive force, viscosity, drug content, spreadability, gelation time and Fourier Transform Infrared (FTIR) compatibility studies.
The results indicates that formula F29 and F30 have best gelation temperatures (33°C, 32°C) gel strength (1.5h,2h) mucoadhesive force of (17.1, 23.4 dyne/cm2 ) and in-vitro drug release (98.2%, 100%) respectively during 3.5h and gelation, time about 10 seconds for both formulas and FTIR spectrum study show absence of important interaction between secnidazole and the polymers used.
References
References
Saini R, Marawar P, Saini S. Periodontitis, a true infection. J Glob Infect Dis. 2009;1(2):149–50.
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809–20.
Haytac MC, Ozcelik O, Mariotti A. Periodontal disease in men. Periodontol 2000. 2013;61(1):252–65.
Khan S, Khalid T, Awan KH. Chronic periodontitis and smoking: Prevalence and dose-response relationship. Saudi Med J. 2016;37(8):889–94.
Flemmig TF. Periodontitis. Ann Periodontol. 1999;4(1):32–8.
Loesche WJ, Baron S. Microbiology of Dental Decay and Periodontal Disease. In: Medical Microbiology. Galveston TX; 1996.
Benachinmardi KK, Nagamoti J, Kothiwale S, Metgud SC. Microbial Flora in Chronic Periodontitis: Study at a Tertiary Health Care Center from North Karnataka. J Lab Physicians. 2015;7(01):049–54.
Belstrøm D, Sembler-Møller ML, Grande MA, Kirkby N, Cotton SL, Paster BJ, et al. Microbial profile comparisons of saliva, pooled and site-specific subgingival samples in periodontitis patients. PLoS One. 2017;12(8):1–11.
Ximénez-Fyvie LA, Haffajee AD, Socransky SS. Microbial composition of supra- and subgingival plaque in subjects with adult periodontitis. J Clin Periodontol. 2000;27(10):722–32.
Rams TE, Sautter JD, van Winkelhoff AJ. Comparative in vitro resistance of human periodontal bacterial pathogens to tinidazole and four other antibiotics. Antibiotics. 2020;9(2).
Haris M, Panickal DM. Role of Metronidazole as a Local Drug Delivery in the Treatment of Periodontitis:A Review. Int J Oral Heal Med Res. 2017;3(July):141–5.
Tally FP, Goldin B, Sullivan NE. Nitroimidazoles: In vitro activity and efficacy in anaerobic infections. Scand J Infect Dis. 1981;13(Suppl. 26):46–53.
Yadav R, Kanwar IL, Haider T, Pandey V, Gour V, Soni V. In situ gel drug delivery system for periodontitis: an insight review. Futur J Pharm Sci. 2020;6(1):1–13.
Gillis JC, Wiseman LR. Secnidazole. Drugs. 1996;51(4):621–38.
National Center for Biotechnology Information. Secnidazole [Internet]. PubChem Compound Summary for CID 71815. 2021. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Secnidazole
Bonner J. Use of secnidazole in treatment of dental infections. 7691831, 2012. p. 9.
Rajeshwari HR, Dhamecha D, Jagwani S, Rao M, Jadhav K, Shaikh S, et al. Local drug delivery systems in the management of periodontitis: A scientific review. J Control Release. 2019;307(August):393–409.
Pragati S, Ashok S, Kuldeep S. Recent advances in periodontal drug delivery systems. Int J drug Deliv. 2009;1(1):1–14.
Arun Karthick R, Ramya Devi D, Vedha Hari BN. Investigation of sustained release mucoadhesive in-situ gel system of Secnidazole for the persistent treatment of vaginal infections. J Drug Deliv Sci Technol. 2018;43(July 2017):362–8.
Narayana RC, Harish NM, Gulzar A M, Prabhakara P, Singh AK, Subrahmanyam EVS. Formulation and in vitro evaluation of in situ gels containing secnidazole for vaginitis. Yakugaku Zasshi. 2009;129(5):569–74.
Priyanka M, Meenakshi B. Study of secnidazole-serratiopeptidase alginate/HPMC gels for periodontal delivery. Int J PharmTech Res. 2011;3(3):1488–94.
Gad HA, El-Nabarawi MA, Abd El-Hady SS. Formulation and evaluation of secnidazole or doxycycline dento-oral gels. Drug Dev Ind Pharm. 2008;34(12):1356–67.
Gad HA, El-Nabarawi MA, Abd El-Hady SS. Formulation and evaluation of PLA and PLGA in situ implants containing secnidazole and/or doxycycline for treatment of periodontitis. AAPS PharmSciTech. 2008;9(3):878–84.
Alexandridis P, Alan Hatton T. Poly(ethylene oxide)poly(propylene oxide)poly(ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids Surfaces A Physicochem Eng Asp. 1995;96(1–2):1–46.
Bodratti AM, Alexandridis P. Formulation of Poloxamers for Drug Delivery. J Funct Biomater. 2018;9(11):1–24.
Gilbert JC, Washington C, Davies MC, Hadgraft J. The behaviour of Pluronic F127 in aqueous solution studied using fluorescent probes. Int J Pharm. 1987;40(1–2):93–9.
Bodratti AM, Alexandridis P. Formulation of poloxamers for drug delivery. J Funct Biomater. 2018;9(1).
Chen Y, Lee J-H, Meng M, Cui N, Dai C-Y, Jia Q, et al. An Overview on Thermosensitive Oral Gel Based on Poloxamer 407. Materials (Basel). 2021;14(16):4522.
Giuliano E, Paolino D, Fresta M, Cosco D. Mucosal applications of poloxamer 407-based hydrogels: An overview. Pharmaceutics. 2018;10(3):1–26.
Qian Y, Wang F, Li R, Zhang Q, Xu Q. Preparation and evaluation of in situ gelling ophthalmic drug delivery system for methazolamide. Drug Dev Ind Pharm. 2010;36(11):1340–7.
Odbole MD, There PW, Dangre PV. Formulation and optimization of prolonged release nasal in situ gel for treatment of migraine. Indo Am J Pharm Res. 2014;4(3):1320–32.
A.K. AliAllah, Abd-AlHammid SN. Preparation and Evaluation of Chloramphenicol as Thermosensitive Ocular in- situ Gel.pdf. Iraqi J Pharm Sci. 2012;21(2):98–105.
Kurniawansyah IS, Sopyan I, Wathoni N, Fillah DL, Praditya RU. Application and characterization of in situ gel. Int J Appl Pharm. 2018;10(6):34–7.
Sanjana A, Ahmed MG, Gowda J. Preparation and evaluation of in-situ gels containing hydrocortisone for the treatment of aphthous ulcer. J Oral Biol Craniofacial Res. 2021;11(2):269–76.
Marques MRC, Loebenberg R, Almukainzi M. Simulated Fluids. Dissolution Technol. 2011;18(3):15–28.
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm - Drug Res. 2010;67(3):217–23.
Garala K, Joshi P, Patel J, Ramkishan A, Shah M. Formulation and evaluation of periodontal in situ gel. Int J Pharm Investig. 2013;3(1):29.
El-Feky YA, Fares AR, Zayed G, El-Telbany RFA, Ahmed KA, El-Telbany DFA. Repurposing of nifedipine loaded in situ ophthalmic gel as a novel approach for glaucoma treatment. Biomed Pharmacother. 2021;142(July):112008.
Ramadan EM, Borg TM, Elkayal MO. Formulation and evaluation of novel mucoadhesive ketorolac tromethamine liquid suppository. African J Pharm Pharmacol. 2009;3(4):124–32.
Shastri DH, Prajapati ST, Patel LD. Design and Development of Thermoreversible Ophthalmic In Situ Hydrogel of Moxifloxacin HCl. Curr Drug Deliv. 2010;7(3):238–43.
Prabhu A, Koland M. Development and Evaluation of an in Situ Thermogelling System of Ofloxacin for Controlled Ocular Delivery. Asian J Pharm Clin Res. 2019;12(3):567–70.
Dewan M, Bhowmick B, Sarkar G, Rana D, Bain MK, Bhowmik M, et al. Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations. Int J Biol Macromol. 2015;72:706–10.
Li L. Thermal gelation of methylcellulose in water: Scaling and thermoreversibility. Macromolecules. 2002;35(15):5990–8.
Parthiban KG, Manivannan R, Kumar BS, Ahasan MB. Formulation and Evaluation of Ketorolac Ocular pH-Triggered In-Situ Gel. Int J Drug Dev Res. 2016;2(2):2010.
Shau PA, Dangre P V, Potnis V V. Formulation of thermosensitive in situ otic gel for topical management of otitis media. Indian J Pharm Sci. 2015;77(6):764.
Semalty A, Semalty M, Nautiyal U. Formulation and evaluation of mucoadhesive buccal films of enalapril maleate. Indian J Pharm Sci. 2010;72(5):571–5.
Kassab HJ, Khalil YI. 5-Fluorouracil mucoadhesive liquid suppository formulation and evaluation. 2014;
Thomas LM, Khasraghi AH, Saihoo AH. Preparation and evaluation of lornoxicam in situ gelling liquid suppository. Drug Invent Today. 2018;10(8):1556–63.
Joshi SC. Sol-Gel Behavior of Hydroxypropyl Methylcellulose (HPMC) in Ionic Media Including Drug Release. Materials (Basel). 2011;4:1861–905.
Godbole MD, P.W.There, P.V.Dangre. Formulation and Optimization of Prolonged Release Nasal in Situ. Indo Am J Pharm Res. 2014;4(02):1320–32.
Gupta C, Juyal V, Nagaich U. Formulation, optimization, and evaluation of in-situ gel of moxifloxacin hydrochloride for ophthalmic drug delivery. Int J Appl Pharm. 2019;11(4):147–58.
Farid RM, Etman MA, Nada AH, Ebian AEAR. Formulation and in vitro evaluation of salbutamol sulphate in situ gelling nasal inserts. AAPS PharmSciTech. 2013;14(2):712–8.
Ali T, Shoaib MH, Yousuf RI, Jabeen S, Muhammad IN, Tariq A. Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets. Brazilian J Pharm Sci. 2014;50(4):799–818.
U.S. Pharmacopoeial Convention. (905) Uniformity of Dosage Units. Stage 6 Harmonization. In: The United States Pharmacopeial Convention. 2011.
Mortazavi SA, Moghimi HR. Effect of surfactant type and concentration on the duration of mucoadhesion of carbopol 934 and HPMC solid compacts. Iran J Pharm Res. 2003;2(4):191–9.
Godbole MD, There PW, Dangre P V. Formulation and optimization of prolonged release nasal in situ gel for treatment of migraine. Indo Am J Pharm Res. 2014;4(3):1320–32.
Dhawan S, Singla AK, Sinha VR. Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods. AAPS PharmSciTech. 2004;5(4):Article 67.
Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev. 2005;57(11):1556–68.
Al-Wiswasi NN, Al-Khedairy EB. View of Formulation and in vitro Evaluation of In-situ Gelling Liquid Suppositories for Naproxen. Iraqi J Pharm Sci. 2008;17(1):31–8.
Hirun N, Tantishaiyakul V, Sangfai T, Ouiyangkul P, Li L. In situ mucoadhesive hydrogel based on methylcellulose/xyloglucan for periodontitis. J Sol-Gel Sci Technol. 2019;89(2):531–42.
Kobayashi K, Huang C, Lodge TP. Thermoreversible gelation of aqueous methylcellulose solutions. Macromolecules. 1999;32(21):7070–7.
Shaikh R, Raj Singh T, Garland M, Woolfson A, Donnelly R. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011;3(1):89–100.
Harish NM, Prabhu P, Charyulu RN, Gulzar MA, Subrahmanyam EVS. Formulation and evaluation of in situ gels containing clotrimazole for oral candidiasis. Indian J Pharm Sci. 2009;71(4):421–7.
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512)
This work is licensed under a Creative Commons Attribution 4.0 International License.
