Approaches to the selection of excipients for dental gel with cetylpyridinium chloride

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The aim of the study was to determine the excipients influence on the characteristics of gels with cetylpyridinium chloride and to select the dental gel formulation gelation agents promising for the development of dental gel compositions. Hereby, the properties of the active pharmaceutical ingredient, characteristics of the specific gelation agents, as well as their influence on stability, biopharmaceutical and application properties of gels, were taken into account.

Materials and methods. In this study, polymers with various gelation mechanisms were considered. Their compatibility with cetylpyridinium chloride as well as storing kinetic and colloid kinds of stability, pH of aqueous solutions, spreadability and textural properties, a penetration ability by the agar diffusion method, an osmotic activity and rheological properties of the gels, were examined. For a complex evaluation of gel compositions study results, a desirability function was used.

Results. Stable homogenous dental gels with cetylpyridinium chloride can be obtained by using 25% poloxamer 407 and 5.0% high molecular weight chitosan as the basis.

The addition of poloxamer 188 to high molecular weight chitosan gels can produce stable systems with improved textural characteristics as well as increase their osmotic activity. Agar and low molecular weight chitosan addition significantly decrease, whereas poloxamer 188 and various molecular weight polyethyleneglycol increase the osmotic activity of 25% poloxamer 407 gels which are also characterized by a high penetration ability.

Conclusion. A complex evaluation of biopharmaceutical, physicochemical and application properties of the gels made it possible to establish that combinations of poloxamer 407 with polyvinylpyrrolidone, agar, and low molecular weight chitosan, can be recommended as a base for a dental gel with cetylpyridinium chloride.

作者简介

Elena Zagorulko

Saint Petersburg State Chemical and Pharmaceutical University

编辑信件的主要联系方式.
Email: elena.zagorulko@pharminnotech.com
ORCID iD: 0000-0003-0103-3560

Candidate of Sciences (Pharmacy), research associate at the Research Department, senior lecturer at the Department of Industrial Drug Technology

俄罗斯联邦, Bld. A, 14, Prof. Popov Str., St. Petersburg, 197376

Aleksandra Karavaeva

Saint Petersburg State Chemical and Pharmaceutical University

Email: alessandra.karavaeva.96.5@mail.ru

student of Pharmaceutical Department

俄罗斯联邦, Bld. A, 14, Prof. Popov Str., St. Petersburg, 197376

参考

  1. Zdorov’e polosti rta. Vsemirnaja organizacija zdravoohranenija [Oral health. World Health Organization]. Published 2018. Available from: https://www.who.int/ru/news-room/fact-sheets/detail/oral-health [cited 2019 Jul 09]. Russian
  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 Sep;83(9):661–9. DOI: /S0042-96862005000900011.
  3. Gosudarstvennyj reestr lekarstvennyh sredstv [The state register of medicines] Available from: https://grls.rosminzdrav.ru/Default.aspx [cited 2019 Jul 09]. Russian
  4. Rjazanova TK, Varina NR, Kurkin VA, Petruhina IK, Avdeeva EV, Klimova LD, Lapina AS. Issledovanie nomenklatury lekarstvennyh sredstv dlja mestnogo lechenija infekcionno-vospalitel’nyh zabolevanij polosti rta i gorla, predstavlennyh na farmacevticheskom rynke Rossijskoj Federacii [Research of the nomenclature of medicines for local treatment of infectious inflammatory diseases of the oral cavity and throat presented in the pharmaceutical market of the russian federation] // Medicinskij al’manah – Medical Almanac. 2016;5 (45):207–210. Russian
  5. Lebedinskaja EA, Utkina NP, Merzlova NB. Ocenka jeffektivnosti preparatov, soderzhashhih cetilpiridinija hlorid, v mestnoj terapii ostryh faringitov, laringitov i kataral’noj anginy u detej [Assessment of the efficacy of cetylpyridinium chloride-containing drugs in topical treatment of acute pharyngitis, laryngitis and catarrhal tonsillitis in children] // Voprosy sovremennoi pediatrii – Current Pediatrics. 2013;12 (1):177–180 doi: 10.15690/vsp.v12i1.577. Russian
  6. Department of Health and Human Service (US). Food and Drug Administration. 21 CFR Part 356. Oral health care drug products for over-the-counter human use; anti-gingivitis/anti-plaque drug products; establishment of a monograph; proposed rules. Federal Register 2003 May 29. Available from: https://federalregister.gov/a/03-12783
  7. Cetylpyridinium chloride. – Available from: https://pubchem.ncbi.nlm.nih.gov/compound/cetylpyridinium_chloride#section=Pharmacology-and-Biochemistry [cited 2019 Jul 09]
  8. Karavaeva AS, Zagorulko EY. Lekarstvennye preparaty s cetilpiridinija hloridom, primenjaemye dlja lechenija infekcionno-vospalitel’nyh zabolevanij polosti rta i glotki [Pharmaceutical preparations with cetylpyridinium chloride for oral cavity infectious and inflammatory diseases treatment] // Sb. mat. VI Vserossijskoj nauch.-prakt. konf. s mezhd. uch. «Innovacii v zdorov’e nacii», Sankt-Peterburg, 2018. SPb.: Izd-vo SPHFU: 131–135. Russian
  9. Rösing CK, Cavagni J, Gaio EJ, Muniz FWMG, Ranzan N, Oballe HJR, Friedrich SA, Severo RM, Stewart B, Zhang YP. Efficacy of two mouthwashes with cetylpyridinium chloride: a controlled randomized clinical trial. Braz Oral Res. 2017 Jul 3;31:e47. doi: 10.1590/1807-3107BOR-2017.vol31.0047.
  10. Fini A, Bergamante V, Ceschel GC. Mucoadhesive gels designed for the controlled release of chlorhexidine in the oral cavity. Pharmaceutics. 2011 Sep 27;3(4):665–79. doi: 10.3390/pharmaceutics3040665.
  11. Elmowafy E, Cespi M, Bonacucina G, Soliman ME. In situ composite ion-triggered gellan gum gel incorporating amino methacrylate copolymer microparticles: a therapeutic modality for buccal applicability. Pharm Dev Technol. 2019 Dec;24(10):1258–1271. doi: 10.1080/10837450.2019.1659314.
  12. Jain HK, Swami PN, Gujar KN. Formulation and evaluation of an antimicrobial mucoadhesive dental gel of azadirachta indica and glycyrrhiza glabra. Int J App Pharm. 2019 Mar 7;11(2):176–84. doi: 10.22159/ijap.2019v11i2.29723.
  13. Kassab HJ, Thomas LM, Jabir SA. Development and physical characterization of a periodontal bioadhesive gel of gatifloxacin. Int J App Pharm. 2017 May 1;9(3):31–6. doi: 10.22159/ijap.2017v9i3.17056.
  14. Raszewski Z, Nowakowska-Toporowska A, Weżgowiec J, Nowakowska D. Design and characteristics of new experimental chlorhexidine dental gels with anti-staining properties. Adv Clin Exp Med. 2019 Jul;28(7):885–890. doi: 10.17219/acem/94152.
  15. Michał T, Katarzyna S, Małgorzata P, Jakub S, Adrian W, Daniel M G, Monika T, Katarzyna W. Hydrogel Containing an Extract of Tormentillae rhizoma for the Treatment of Bioflim-Related Oral Diseases. Nat Prod Commun. 2017 Mar;12(3):417–421. doi: 10.1177/1934578X1701200328.
  16. Babickaite L, Ramanauskiene K, Grigonis A, Ivaskiene M, Daunoras G, Klimiene I, Virgailis M, Zamokas G, Inkeniene AM, Matusevicius AP. Determination of antimicrobial activity of chlorhexidine gel. Acta Pol Pharm. 2016 Nov;73(6):1623–1630.
  17. Ashrafi B, Rashidipour M, Marzban A, Soroush S, Azadpour M, Delfani S, Ramak P. Mentha piperita essential oils loaded in a chitosan nanogel with inhibitory effect on biofilm formation against S. mutans on the dental surface. Carbohydrate Polymers. 2019; 212: 142–149. doi: 10.1016/j.carbpol.2019.02.018.
  18. Rashid M, Hossain MF, Nounou M, Rahman M, Sarkar S, Adeyemo A, Mullins R. Compounding and Comparative Study of a Superior, Faster, and More Adaptable Lidocaine Dental Gel Formulation. Int J Pharm Compd. 2019 May–Jun;23(3):250–257.
  19. Aslani A, Malekpour N. Design, formulation, and physicochemical evaluation of periodontal propolis mucoadhesive gel. Dent Res J (Isfahan). 2016 Nov-Dec;13(6):484-493. doi: 10.4103/1735-3327.197037.
  20. Karavaeva A.S. Vybor koncentracii poloksamera kak osnovy stomatologicheskogo gelja s cetilpiridinija hloridom [The selection of poloxamer concentration as a base for the dental gel with cetylpyridinium chloride] // Sbornik materialov IX Vserossijskoj nauchnoj konferencii studentov i aspirantov s mezhdunarodnym uchastiem «Molodaja farmacija – potencial budushhego», Sankt-Peterburg, 2019. SPb.: Izd-vo SPHFU: 259–263. Russian
  21. Mirtič J, Kogej K, Baumgartner S, Smistad G, Kristl J, Hiorth M. Development of Cetylpyridinium-Alginate Nanoparticles: A Binding and Formulation Study. Int J Pharm. 2016 Sep 25;511(2):774–84. doi: 10.1016/j.ijpharm.2016.07.065.
  22. Matsuo K, Yoshihara K, Nagaoka N, Makita Y, Obika H, Okihara T, Matsukawa A, Yoshida Y, Van Meerbeek B. Rechargeable anti-microbial adhesive formulation containing cetylpyridinium chloride montmorillonite. Acta Biomaterialia. 2019; 100: 388–397. doi: 10.1016/j.actbio.2019.09.045.
  23. Ali J, Khar R, Ahuja A, Kalra R. Buccoadhesive erodible disk for treatment of oro-dental infections: design and characterisation. Int J Pharm. 2002 May 15;238(1–2):93-103. doi: 10.1016/s0378-5173(02)00059-5.
  24. Collins AE, Deasy PB. Bioadhesive lozenge for the improved delivery of cetylpyridinium chloride. J Pharm Sci. 1990 Feb;79(2):116–9. doi: 10.1002/jps.2600790208.
  25. Nafee NA, Boraie MA, Ismail FA, Mortada LM. Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride. Acta Pharm. 2003 Sep;53(3):199–212.
  26. Mittal K.L. Progress in Adhesion and Adhesives. New Jersey: John Wiley & Sons, Inc, 2015: 496. doi: 10.1002/9781119162346
  27. Gad S. C. Pharmaceutical Manufacturing Handbook. Production and Processes. New Jersey: John Wiley & Sons, Inc, 2008: 1370. doi: 10.1002/9780470259818.
  28. Russo E, Selmin F, Baldassari S. A focus on mucoadhesive polymers and their application in buccal dosage forms. Journal of Drug Delivery Science and Technology. 2016; 32: 113–125. doi: 10.1016/j.jddst.2015.06.016
  29. Chatterjee B, Amalina N, Sengupta P, Mandal UK. Mucoadhesive Polymers and Their Mode of Action: A Recent Update. Journal of Applied Pharmaceutical Science. 2017; 7 (05): 195–203. doi: 10.7324/JAPS.2017.70533.
  30. Thakur VK, Thakur MK. Handbook of Polymers for Pharmaceutical Technologies: Structure and Chemistry, Vol. 1. New Jersey: John Wiley & Sons, Inc., 2015: 529. doi: 10.1002/9781119041375.
  31. Tencova A.I., Aljushin M.T. Polimery v farmacii [Polymers in pharmacy] M.: Medicina, 1985: 256. Russian
  32. Zagorulko EY, Teslev AA. Vybor vspomogatel’nyh veshhestv i opredelenie harakteristik gelja dlja prijoma vnutr’ «Ralitin» [Excipients selection and characterization for «Ralitin» gel for oral administration]// Razrabotka i registracija lekarstvennyh sredstv – Drug development & registration. 2018; 3: 20–28. Russian
  33. Tencova A.I., Greckij V.M. Sovremennye aspekty issledovanija i proizvodstva mazej. [Modern aspects of research and production of ointments.] – M.: Medicina. 1980: 192. Russian
  34. Kuznecova LS, Lihota TT. Razrabotka sostava, tehnologii i analiz karandashej medicinskih s kamforoj [Working out of structure, technology and the analysis of pencils medical with camphor] Fundamental’nye issledovanija – Fundamental research. 2011; 11: 522–525. Russian
  35. Iliev K.I., Bacheva N.N., Larionov L.P. Biofarmacevticheskie i farmakologicheskie issledovanija mazi «Lidodiklozol’» [Biopharmaceutical and pharmacological research ointment «Lidodiklozol»] // Medicinskaja nauka i obrazovanie Urala – Medical science and education of the Urals. 2016; 2: 127–131. Russian
  36. State Pharmacopoeia of the Russian Federation. XIVed. Vol. 1. 2018:1814. Available from: http://resource.rucml.ru/feml/pharmacopia/14_1/ HTML/index.html [cited 2019 Jan 09]. Russian
  37. Harrington EC. The desirability function // Industrial Quality Control. 1965; 21 (10): 494–498.
  38. Fakhari A, Corcoran M, Schwarz A. Thermogelling properties of purified poloxamer 407. Heliyon. 2017 Aug 30;3(8):e00390. doi: 10.1016/j.heliyon.2017.e00390.
  39. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res. 2006 Dec;23(12):2709–28. doi: 10.1007/s11095-006-9104-4.
  40. Akca G, Özdemir A, Öner ZG, Şenel S. Comparison of different types and sources of chitosan for the treatment of infections in the oral cavity. Research on Chemical Intermediates. 2018; 44(8): 4811–4825. doi: 10.1007/s11164-018-3338-8.
  41. Pellá MCG, Lima-Tenório MK, Tenório-Neto ET, Guilherme MR, Muniz EC, Rubira AF. Chitosan-based hydrogels: From preparation to biomedical applications. Carbohydr Polym. 2018 Sep 15;196:233–245. doi: 10.1016/j.carbpol.2018.05.033.
  42. Denisov A. B. Sljuna i sljunnye zhelezy [Saliva and salivary glands]. M.: RAMN, 2009: 472. Russian

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2. Figure 1 – Dependence of the absorbed isotonic solution mass fraction on the time of gel dialysis. Note: А – compositions 1, 7, 8, 10, 12 and 15; B – compositions 4, 8, 11, 13 and 14

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3. Figure 2 – Viscosity curves for compositions 7, 12 (A) and 11, 14 (B) at 20°С

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