Modern aspects of the development of bioadhesive dosage forms for the oral cavity (review)

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The creation of dosage forms with the ability to bioadhesive is an urgent direction in the development of pharmaceutical technology. This review systematizes modern developments of bioadhesive drugs for use in the oral cavity, including films, gels, tablets and micro-/nanoparticles. Special attention is paid to bioadhesive polymers, their systematization and description of properties and methods of inclusion in the composition of dosage forms. The key aspects of the structure of the oral mucosa that determine the effectiveness of bioadhesion and methods for measuring mucoadhesive properties (in vitro and in vivo), including stretching tests, rheological methods, the use of flow systems, etc. are considered. Examples of commercial drugs available on the Russian market and variants of formulations of dosage forms described in scientific publications are given. The review also addresses the issue of standardization of testing methods for these dosage forms, including the use of synthetic and natural mucosal analogues. In general, the development of bioadhesive medicines for the oral cavity opens up new opportunities for the treatment of local and systemic diseases, combining ease of use, prolonged effect and reduction of systemic adverse reactions.

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作者简介

Maria Anurova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

编辑信件的主要联系方式.
Email: anurova_m_n@staff.sechenov.ru
ORCID iD: 0000-0002-7649-9616

PhD (Pharm.), Associate Professor of the Department of Pharmaceutical Technology at the A.P. Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya St., 8, Moscow, 119991

Kirill Petrulenko

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: kerjakowski@yandex.ru
ORCID iD: 0009-0000-6828-4976

is a postgraduate student at the Department of Pharmaceutical Technology at the A.P. Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya St., 8, Moscow, 119991

Alexey Kuzmin

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: repzcraft@gmail.com
ORCID iD: 0009-0004-0711-6310

is a postgraduate student at the Department of Pharmaceutical Technology at the A.P. Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya St., 8, Moscow, 119991

Ivan Krasnyuk

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: krasnyuki@mail.ru
ORCID iD: 0000-0002-7242-2988

Doctor of Pharmaceutical Sciences, Professor, Head of the Department of Pharmaceutical Technology at the A.P. Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya St., 8, Moscow, 119991

Natalia Demina

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: demina_n_b@staff.sechenov.ru
ORCID iD: 0000-0003-4307-8791

Doctor of Pharmaceutical Sciences, Professor of the Department of Pharmaceutical Technology at the A.P. Nelyubin Institute of Pharmacy

俄罗斯联邦, Trubetskaya St., 8, Moscow, 119991

参考

  1. Kumar K., Dhawan N., Sharma H., Vaidya S., Vaidya B. Bioadhesive polymers: Novel tool for drug delivery. Artif Cells Nanomed Biotechnol. 2014; 42 (4): 274–83. doi: 10.3109/21691401.2013.815194
  2. Bassi da Silva J., de Ferreira S.B.S., de Freitas O., Bruschi M.L. A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems. Drug Dev Ind Pharm. 2017; 43(7): 1053–70. doi: 10.1080/03639045.2017.1313858
  3. Sheoran R. Buccal drug delivery system: A review. International J. of Pharmaceutical Sciences Review and Research. 2018; 50 (1): 40–6.
  4. Киржанова Е.А., Хутоярский В.В., Балабушевич Н.Г., Харенко А.В., Демина Н.Б. Методы анализа мукоадгезии: от фундаментальных исследований к практическому применению в разработке лекарственных форм. Разработка и регистрация лекарственных средств. 2014; 3 (8): 66–80. [Kirzhanova E.A., Khutoyarskiy V.V., Balabushevich N.G., Kharenko A.V., Demina N.B. Methods of mucoadhesion analysis: from fundamental research to practical application in the development of dosage forms. Razrabotka i registraciya lekarstvennyh sredstv. 2014; 3 (8): 66–80 (in Russian)]
  5. Shaikh R., Singh T.R.R., Garland M.J., Woolfson A.D., Donnelly R.F. Mucoadhesive drug delivery systems. J. Pharm. Bioallied Sci. 2011; 3 (1): 89–100. doi: 10.4103/0975-7406.76478
  6. El Knidri H., Belaabed R., Addaou A., Laajeb A., Lahsini A. Extraction, chemical modification and characterization of chitin and chitosan. Int. J. Biol. Macromol. 2018; 120 (Pt B): 1181–9. doi: 10.1016/j.ijbiomac.2018.08.139
  7. Pamlényi K., Kristó K., Sovány T., Regdon G. Jr. Development and evaluation of bioadhesive buccal films based on sodium alginate for allergy therapy. Heliyon. 2022; 8 (8): e10364. doi: 10.1016/j.heliyon.2022.e10364
  8. Zhao X., Chen S., Lin Z., Du C. Reactive electrospinning of composite nanofibers of carboxymethyl chitosan cross-linked by alginate dialdehyde with the aid of polyethylene oxide. Carbohydr Polym. 2016; 148: 98–106. doi: 10.1016/j.carbpol.2016.04.051
  9. D'Souza A.A., Shegokar R. Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications. Expert Opin Drug Deliv. 2016; 13 (9): 1257–75. doi: 10.1080/17425247.2016.1182485
  10. Sriamornsak P. Application of pectin in oral drug delivery. Expert Opin Drug Deliv. 2011; 8 (8): 1009–23. doi: 10.1517/17425247.2011.584867
  11. Ahmady A.R., Abu Samah N.H. A review: Gelatine as a bioadhesive material for medical and pharmaceutical applications. Int J Pharm. 2021; 608: 121037. doi: 10.1016/j.ijpharm.2021.121037
  12. Brannigan R.P., Khutoryanskiy V.V. Progress and current trends in the synthesis of novel polymers with enhanced mucoadhesive properties. Macromol Biosci. 2019; 19 (10): e1900194. doi: 10.1002/mabi.201900194
  13. Семина И.И., Байчурина А.З. Изучение безвредности применения инновационных пероральных систем доставки лекарственных веществ на основе интерполиэлектролитных комплексов с использованием полимеров фармацевтического назначения Carbopol® и Eudragit®. Фундаментальные исследования. 2014; 12–5: 982–6. [Semina I.I., Baichurina A.Z. The study of the harmlessness of the use of innovative oral drug delivery systems based on interpolyelectrolyte complexes using pharmaceutical polymers Carbopol® and Eudragit®. Fundamental'nye issledovaniya. 2014; 12–5: 982–6 (in Russian)]
  14. Dos Santos J., Da Silva G.S. Eudragit®: A versatile family of polymers for hot melt extrusion and 3D printing processes in pharmaceutics. Pharmaceutics. 2021; 13 (9): 1424. doi: 10.3390/pharmaceutics13091424
  15. Patra C.N., Priya R., Swain S., Jena G.K. Pharmaceutical significance of Eudragit: A review. Future J. Pharm. Sci. 2017; 3 (1): 33–45. doi: 10.1016/j.fjps.2017.02.001
  16. Obeidat W.M., Nokhodchi A., Alkhatib H.S. Evaluation of matrix tablets based on Eudragit® E100/Carbopol® 971P combinations for controlled release and improved compaction properties of water soluble model drug paracetamol. AAPS PharmSciTech. 2015; 16 (5): 1169–79. doi: 10.1208/s12249-015-0301-5
  17. Zhang Q., Li X., Jasti B.R. Role of physicochemical properties of some grades of hydroxypropyl methylcellulose on in vitro mucoadhesion. Int J. Pharm. 2021; 609: 121218. doi: 10.1016/j.ijpharm.2021.121218
  18. Zhu Z., Zhai Y., Zhang N., Leng D., Ding P. The development of polycarbophil as a bioadhesive material in pharmacy. Asian J. Pharm. Sci. 2013; 8 (4): 218–27. doi: 10.1016/j.ajps.2013.09.003
  19. Kumar V., Dantuluri A.K., Liu Y., During T. Hydroxyethylcellulose as a versatile viscosity modifier in the development of sugar-free, elegant oral liquid formulations. International Journal of Current Research in Chemistry and Pharmaceutical Sciences. 2023; 10 (4): 1–23. doi: 10.22192/ijcrcps.2023.10.04.001
  20. Rahman M.S., Hasan M.S., Nitai A.S., Nam S., Karmakar A.K., Ahsan M.S., Shiddiky M.J.A., Ahmed M.B. Recent developments of carboxymethyl cellulose. Polymers (Basel). 2021; 13 (8): 1345. doi: 10.3390/polym13081345
  21. Madni A., Khalid A., Wahid F., Ayub H., Khan R., Kousar R. Preparation and applications of guar gum composites in biomedical, pharmaceutical, food, and cosmetics industries. Curr Nanosci. 2021; 17 (3): 365–79. doi: 10.2174/1573413716999201110142551
  22. Chaturvedi S., Kulshrestha S., Bhardwaj K., Jagir R. A review on properties and applications of xanthan gum. In: Microbial Polymers: Applications and Ecological Perspectives. 2021; 87–107. doi: 10.1007/978-981-16-0045-6_4
  23. Qi X., Tester R.F. Bioadhesive properties of β-limit dextrin. J Pharm Pharm Sci. 2011; 14 (1): 60–6. doi: 10.18433/J3459B
  24. Dey A., Bhattacharya P., Neogi S. Bioadhesives in biomedical applications: A critical review. In: Progress in Adhesion and Adhesives. 2021; 6: 131–53. doi: 10.1002/9781119846703.ch5
  25. Ivarsson D., Wahlgren M. Comparison of in vitro methods of measuring mucoadhesion: ellipsometry, tensile strength and rheological measurements. Colloids Surf B Biointerfaces. 2012; 92: 353–9. doi: 10.1016/j.colsurfb.2011.12.020
  26. Mackie A.R., Goycoolea F.M., Menchicchi B., Caramella C.M., Saporito F., Lee S., Stephansen K., Chronakis I.S., Hiorth M., Adamczak M., Waldner C., Schwarz A., Inngjerdingen K.T. Innovative methods and applications in mucoadhesion research. Macromol Biosci. 2017; 17 (8): 1600534. doi: 10.1002/mabi.201600534
  27. Woertz C., Preis M., Breitkreutz J., Kleinebudde P. Assessment of test methods evaluating mucoadhesive polymers and dosage forms: An overview. Eur J Pharm Biopharm. 2013; 85 (3 Pt B): 843–53. doi: 10.1016/j.ejpb.2013.06.023
  28. Gyarmati B., Stankovits G., Szilágyi B.A., Galata D.L., Gordon P., Szilágyi A. A robust mucin-containing poly(vinyl alcohol) hydrogel model for the in vitro characterization of mucoadhesion of solid dosage forms. Colloids Surf B Biointerfaces. 2022; 213: 112406. doi: 10.1016/j.colsurfb.2022.112406
  29. Cook M.T., Khutoryanskiy V.V. Mucoadhesion and mucosa-mimetic materials–A mini-review. Int. J. Pharm. 2015; 495 (2): 991–8. doi: 10.1016/j.ijpharm.2015.09.064
  30. Keely S., Rullay A., Wilson C., Carmichael A., Carrington S., Corfield A., Haddleton D.M., Brayden D.J. In vitro and ex vivo intestinal tissue models to measure mucoadhesion of poly(methacrylate) and N-trimethylated chitosan polymers. Pharm Res. 2005; 22 (1): 38–49. doi: 10.1007/s11095-004-9007-1
  31. Hamed R., Fiegel J. Synthetic tracheal mucus with native rheological and surface tension properties. J. Biomed Mater Res A. 2014; 102A (6): 1788–98. doi: 10.1002/jbm.a.34851
  32. Dinu V., Yakubov G.E., Lim M., Hurst K., Adams G.G., Harding S.E., Fisk I.D. Mucin immobilization in calcium alginate: A possible mucus mimetic tool for evaluating mucoadhesion and retention of flavour. Int. J. Biol. Macromol. 2019; 138: 831–6. doi: 10.1016/j.ijbiomac.2019.07.148
  33. Miyazaki S., Kawasaki N., Nakamura T., Iwatsu M., Hou W.M., Attwood D. Oral mucosal bioadhesive tablets of pectin and HPMC: in vitro and in vivo evaluation. Int. J. Pharm. 2000; 204 (1–2): 127–32. doi: 10.1016/S0378-5173(00)00491-9
  34. Kotadiya R., Karan S. Development of bioadhesive buccal tablets of nicorandil using a factorial approach. Turk J. Pharm. Sci. 2020; 17 (4): 388–97. doi: 10.4274/tjps.galenos.2019.09226
  35. Hoffmann A., Fischer J.T., Daniels R. Development of probiotic orodispersible tablets using mucoadhesive polymers for buccal mucoadhesion. Drug Dev Ind Pharm. 2020; 46 (11): 1753–62. doi: 10.1080/03639045.2020.1831013
  36. Camargo L.G., Remiro P.D.F.R., Rezende G.S., Santos S.D.C., Franz-Montan M., Moraes Â.M. Development of bioadhesive polysaccharide-based films for topical release of the immunomodulatory agent imiquimod on oral mucosa lesions. Eur Polym J. 2021; 151: 110422. doi: 10.1016/j.eurpolymj.2021.110422
  37. Castán H., Ruiz M.A., Clares B., Morales M.E. Design, development and characterization of buccal bioadhesive films of Doxepin for treatment of odontalgia. Drug Deliv. 2015; 22 (6): 869–76. doi: 10.3109/10717544.2014.896958
  38. Kassab H.J., Thomas L.M., Jabir S.A. Development and physical characterization of a periodontal bioadhesive gel of gatifloxacin. Int. J. Appl Pharm. 2017; 9 (3): 31–6. doi: 10.22159/ijap.2017v9i3.7056
  39. Жапаркулова К. А., Ибрагимова Л. Н., Орынбекова С. О., Сейталлиева А. М. Фармацевтическая разработка адгезивной дентальной пасты с маслом зизифоры бунге. Фармация Казахстана. 2016; 10: 34–8. [Zhaparkulova K.A., Ibragimova L.N., Orynbekova S.O., Seitalieva A.M. Pharmaceutical development of adhesive dental paste with ziziphora bunge oil. Farmaciya Kazakhstana. 2016; 10: 34–8 (in Russian)]
  40. Oh M.J., Kim J., Kim J., Lee S., Xiang Z., Liu Y., Koo H., Lee D. Drug-loaded adhesive microparticles for biofilm prevention on oral surfaces. J. Mater Chem B. 2024; 12 (20): 4935–44. doi: 10.1039/D4TB00134F

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2. Fig. 1. Mechanism of mucoadhesion

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3. Fig. 2. Equipment for determining the tensile and tear strength. Note. а – modified lever scale: 1 – is a lever, 2 – is a device for holding DF or AS samples and mucosal samples; 3 – is the surface to which the DF or AS is attached; 4 – is the DF or AS sample; 5 – is the mucous membrane or its equivalent; 6 – is the load; б – Texture Analyzer (LLOYD Instruments, TA plus Ametek, United Kingdom); в – Electronic Tensile Tester GBL-H (GBPI, China); г – dynamic contact angle meter (CY Scientific Instrument, China)

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4. Fig. 3. Flow system with HPLC analysis or fluorescence labeling of mucoadhesive

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