Research Article

Technological development of mucoadhesive film containing poloxamer 407, polyvinyl alcohol and polyvinylpyrrolidone for buccal metronidazole delivery

Laboratory of Research & Development of Drug Delivery Systems, Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, State University of Maringa, Avenida Colombo, nº 5790, 87020-900, Maringa, Brazil

Search for more papers by this author

Rafaela Said dos Santos

https://orcid.org/0000-0002-6473-4869

Search for more papers by this author

Marcos Luciano Bruschi

*Author for correspondence:

E-mail Address: mlbruschi@uem.br

https://orcid.org/0000-0002-4838-5742

Search for more papers by this author

Published Online:5 Jul 2020https://doi.org/10.4155/tde-2020-0031

View article

Abstract

Aim: This work aimed to develop a mucoadhesive film composed of a triblock copolymer (poloxamer 407), polyvinyl alcohol and polyvinylpyrrolidone for buccal modified delivery of metronidazole. Materials & methods: Three film formulations containing different polymer amounts were prepared by solvent casting. They were characterized as physicochemical, mechanical and mucoadhesive properties, and in vitro metronidazole release profiles. Results: Films displayed physicochemical, mechanical and mucoadhesive characteristics dependent of polymeric composition and drug presence. They could rapidly swell and promote the fast drug release (80% in 20 min) that was governed by Fickian diffusion. The films showed total disintegration in less than 90 s and total drug release in 30 min. Conclusion: Therefore, the formulations represent a promising alternative for modifying of buccal metronidazole delivery for pharmaceutical applications.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Chidambaram N, Srivatsava AK. Buccal drug delivery systems. Drug Dev. Ind. Pharm. 21(9), 1009–1036 (1995).
CASGoogle Scholar
2. Bottenberg P, Cleymaet R, Rohrkasten K, Lampert F. Microhardness changes in surface enamel after application of bioadhesive fluoride tablets in situ. Clin. Oral Investig. 4(3), 153–156 (2000).
Medline CASGoogle Scholar
3. Repka MA, Prodduturi S, Stodghill SP. Production and characterization of hot-melt extruded films containing clotrimazole. Drug Dev. Ind. Pharm. 29(7), 757–765 (2003).
Medline CASGoogle Scholar
4. Shojaei AH. Buccal mucosa as a route for systemic drug delivery: A review. J. Pharmceutical Sci. 1(1), 15–30 (1998).
CASGoogle Scholar
5. Bruschi ML, de Freitas O. Oral bioadhesive drug delivery systems. Drug Dev. Ind. Pharm. 31(3), 293–310 (2005).
Medline CASGoogle Scholar
6. Rezaei B, Damiri S. Fabrication of a nanostructure thin film on the gold electrode using continuous pulsed-potential technique and its application for the electrocatalytic determination of metronidazole. Electrochim. Acta. 55, 1801–1808 (2010).
CASGoogle Scholar
7. Bendesky A, Menéndez D, Ostrosky-Wegman P. Is metronidazole carcinogenic? Mutat. Res. Rev. Mutat. Res. 511(2), 133–144 (2002).
Medline CASGoogle Scholar
8. Liu W, Zhang J, Li C, Tang L, Zhang Z, Yang M. A novel composite film derived from cysteic acid and PDDA-functionalized graphene: enhanced sensing material for electrochemical determination of metronidazole. Talanta [Internet]. 104, 204–211 (2013). http://dx.doi.org/10.1016/j.talanta.2012.11.013
Medline CASGoogle Scholar
9. Ferreira AS, Nunes C, Castro A, Ferreira P, Coimbra MA. Influence of grape pomace extract incorporation on chitosan films properties. Carbohydr. Polym. 113, 490–499 (2014).
Medline CASGoogle Scholar
10. Elzatahry AA, Eldin MSM. Preparation and characterization of metronidazole-loaded chitosan nanoparticles for drug delivery application. Polym. Adv. Technol. 19(January), 1040–1047 (2008).
Google Scholar
11. Wu K, Dang X, Hu S, Shaofang L. Electrochemical reduction and voltammetric determination of metronidazole at a nanomaterial thin film coated glassy carbon electrode. Talanta 63, 653–657 (2004).
MedlineGoogle Scholar
12. Mohamed MI, Haider M, Ali MAM. Buccal mucoadhesive films containing antihypertensive drug. J. Chem. Pharm. Res. 3(6), 665–686 (2011).
CASGoogle Scholar
13. Boddupalli BM. Mucoadhesive drug delivery system: an overview. J. Advenced Pharm. Technol. Res. 1(4), 381–387 (2010). •• Review of modified-release systems with mucoadhesive characteristics.
Medline CASGoogle Scholar
14. Aggarwal J, Singh G, Saini S, Rana AC. Fast dissolving films: a novel approach to oral drug delivery. Int. Res. J. Pharm. 2(12), 69–71 (2011). • Characterization of film types according to their release.
CASGoogle Scholar
15. Kajthunyakarn W, Sakloetsakun D, Pongjanyakul T. Sodium caseinate-magnesium aluminum silicate nanocomposite fi lms for modi fi ed-release tablets. Mater. Sci. Eng. C. 92(June), 827–839 (2018).
Medline CASGoogle Scholar
16. Dixit RP, Puthli SP. Oral strip technology: overview and future potential. J. Control. Rel. 139(2), 94–107 (2009). http://dx.doi.org/10.1016/j.jconrel.2009.06.014
Medline CASGoogle Scholar
17. Kalyan S, Bansal M. Recent trends in the development of oral dissolving film. Int. J. PharmTech Res. 4(2), 725–733 (2012).
CASGoogle Scholar
18. Bernin D, Marucci M, Boissier C, Hjärtstam J, Olsson U, Abrahmsén-alami S. Real time MRI to elucidate the functionality of coating films intended for modified release. J. Control. Rel. 312(August), 117–124 (2019).
Google Scholar
19. Soskolone WA, Freidman M. Intra-periodontal pocket drug delivery systems. Drugs Pharm. Sci. 74, 359–379 (1996).
CASGoogle Scholar
20. Ribeiro LNM, Alcântara ACS, Darder M, Aranda P, Araújo-Moreira FM, Ruiz-Hitzky E. Pectin-coated chitosan-LDH bionanocomposite beads as potential systems for colon-targeted drug delivery. Int. J. Pharm. 463(1), 1–9 (2014). http://dx.doi.org/10.1016/j.ijpharm.2013.12.035
Medline CASGoogle Scholar
21. Singh S, Jain S, Muthu MS, Tiwari S, Tilak R. Preparation and evaluation of buccal bioadhesive films containing clotrimazole. AAPS PharmSciTech. 9(2), 660–667 (2008).
Medline CASGoogle Scholar
22. De Araujo DR, Padula C, Cereda CMS et al. Bioadhesive films containing benzocaine: correlation between in vitro permeation and in vivo local anesthetic effect. Pharm. Res. 27(8), 1677–1686 (2010).
MedlineGoogle Scholar
23. Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. Eur. J. Pharm. Biopharm. [Internet] 77(2), 187–199 (2011). http://dx.doi.org/10.1016/j.ejpb.2010.11.023
Medline CASGoogle Scholar
24. Koland M, Charyulu RN, Prabhu P. Mucoadhesive films of losartan potassium for buccal delivery: design and characterization. Indian J. Pharm. Educ. Res. 44(4), 315–323 (2010).
Google Scholar
25. Desai SD, Blanchard J. In vitro evaluation of pluronic F127-based controlled-release ocular delivery systems for pilocarpine. J. Pharm. Sci. 87(2), 226–230 (1998).
Medline CASGoogle Scholar
26. Nita H, Ogawa K. Ophtalmic composition with regulated viscosity. United States patent: US 6511949 B1 (2003).
Google Scholar
27. Taheri A, Atyabi F, Dinarvnd R. Temperature-responsive and biodegradable PVA:PVP k30:poloxamer 407 hydrogel for controlled delivery of human growth hormone (hGH). J. Pediatr. Endocrinol. Metab. 24(3–4), 175–179 (2011).
Medline CASGoogle Scholar
28. Vecchi CF, Bruschi ML. Films composed of polyvinyl alcohol, polyvinylpyrrolidone and poloxamer 407: in-vitro mucoadhesive analysis. Presented at: XVIII Brazilian Materials Research Society Meeting. Balneario Camboriu, SC, Brazil, 22–26 November 2019.
Google Scholar
29. Toledo L de A. Mechanical characterization of propolis films.. Presented at: II Congress of the Brazilian Association of Pharmaceutical Sciences. Buzios, Rio de Janeiro, Brazil, 24–27 September 2014.
Google Scholar
30. Toledo L de A, Bavato MI, Rosseto HC, Cortesi R. Pharmaceutical films made from the waste material from the preparation of propolis extracts: development and characterization. Brazilian J. Pharm. Sci. 51(4), 847–859 (2015).
Google Scholar
31. Deshmane SV, Channawar MA, Chandewar AV, Joshi UM, Biyani KR. Chitosan based sustained release mucoadhesive buccal patches containing verapamil HCL. Int. J. Pharm. Pharm. Sci. 1(Suppl. 1), 216–229 (2009). •• Preparation and characterization methodologies for films.
CASGoogle Scholar
32. Cao N, Yang X, Fu Y. Effects of various plasticizers on mechanical and water vapor barrier properties of gelatin films. Food Hydrocoll. 23(3), 729–735 (2009).
CASGoogle Scholar
33. Ammar HO, Ghorab MM, Mahmoud AA, Shahin HI. Design and in vitro/in vivo evaluation of ultra-thin mucoadhesive buccal film containing fluticasone propionate. AAPS PharmSciTech. 18(1), 93–103 (2017).
Medline CASGoogle Scholar
34. Trastullo R, Abruzzo A, Saladini B et al. Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron. Eur. J. Pharm. Biopharm. 105, 115–121 (2016).
Medline CASGoogle Scholar
35. Nesseem DI, Eid SF, El-Houseny SS. Development of novel transdermal self-adhesive films for tenoxicam, an anti-inflammatory drug. Life Sci. 89(13–14), 430–438 (2011). http://dx.doi.org/10.1016/j.lfs.2011.06.026
Medline CASGoogle Scholar
36. El-kamel AH, Ashri LY, Alsarra IA. Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases. AAPS PharmSciTech. 8(3), 184–194 (2007).
Google Scholar
37. Brito M, Bassi J, Camotti M, Kimura E, Diniz A. Design and characterization of mucoadhesive gelatin-ethylcellulose microparticles for the delivery of curcumin to the bladder. Curr. Drug Deliv. 15(8), 1112–1122 (2018).
MedlineGoogle Scholar
38. Verma N, Chattopadhyay P. Preparation of mucoadhesive patches for buccal administration of metoprolol succinate: in vitro and in vivo drug release and bioadhesion. Trop. J. Pharm. Res. 11(1), 9–17 (2012). • Methodologies for mechanical analysis of films.
CASGoogle Scholar
39. Goodman H, Kanig J. Evaluative procedures for film-forming materials used in pharmaceutical applications. J. Pharmaeutical Sci. 51(1), 77–83 (1962).
MedlineGoogle Scholar
40. de Toledo LAS, Bavato MI, Rosseto HC, Cortesi R, Bruschi ML. Pharmaceutical films made from the waste material from the preparation of propolis extracts: development and characterization. Brazilian J. Pharm. Sci. 51(4), 847–859 (2015).
CASGoogle Scholar
41. Speer I, Steiner D, Thabet Y, Breitkreutz J, Kwade A. Comparative study on disintegration methods for oral film preparations. Eur. J. Pharm. Biopharm. 132, 50–61 (2018).
Medline CASGoogle Scholar
42. De Souza Ferreira SB, De Assis Dias BR, Obregón CS et al. Microparticles containing propolis and metronidazole: in vitro characterization, release study and antimicrobial activity against periodontal pathogens. Pharm. Dev. Technol. 19(2), 173–180 (2014).
MedlineGoogle Scholar
43. Bruschi ML, Jones DS, Panzeri H, Gremião MPD, de Freitas O, Lara EHG. Semisolid systems containing propolis for the treatment of periodontal disease: in vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties. J. Pharm. Sci. 96(8), 2074–2089 (2006).
Google Scholar
44. Rosina CR, Baroni S, Cavalcanti OA. Avaliação das propriedades de intumescimento e permeabilidade de filmes isolados de polimetacrilato contendo polissacarídeo da raiz de Lótus (Nelumbo nucifera). Rev. Bras. Ciências Farm. 40(3), 425–431 (2004).
CASGoogle Scholar
45. Baraker BM, Lobo B. Microstructure of cadmium chloride doped PVA/PVP blend films. Mater. Today Proc. 5(1), 3036–3043 (2018).
CASGoogle Scholar
46. Kreidel RN, Duque DM, Serra CHR et al. Dissolution enhancement and characterization of nimodipine solid dispersions with poloxamer 407 or PEG 6000. J. Dispers. Sci. Technol. 2, 2–20 (2009).
Google Scholar
47. Omkaram I, Sreekanth Chakradhar RP, Lakshmana Rao J. EPR, optical, infrared and Raman studies of VO2+ ions in polyvinylalcohol films. Phys. B Condens. Matter. 388(1–2), 318–325 (2007).
CASGoogle Scholar
48. Abdelrazek EM, El Damrawi G, Al-Shahawy A. Some studies on calcium phosphate embedded in polyvinyl alcohol matrix before and after γ-irradiation. Phys. B Condens. Matter. 405(3), 808–816 (2010).
CASGoogle Scholar
49. Zidan HM, Abdelrazek EM, Abdelghany AM, Tarabiah AE. Characterization and some physical studies of PVA/PVP filled with MWCNTs. J. Mater. Res. Technol. 8(1), 904–913 (2019).
CASGoogle Scholar
50. Ramukutty S, Ramachandran E. Crystal growth by solvent evaporation and characterization of metronidazole. J. Cryst. Growth 351(1), 47–50 (2012).
CASGoogle Scholar
51. Duraikkan V, Sultan AB, Nallaperumal N, Shunmuganarayanan A. Structural, thermal and electrical properties of polyvinyl alcohol/poly(vinyl pyrrolidone)-sodium nitrate solid polymer blend electrolyte. Ionics 24, 139–151 (2018).
CASGoogle Scholar
52. Elashmawi I, Abdelrazek E, Yassin A. Influence of NiCl2/CdCl2 as mixed filler on structural, thermal and electrical properties of PVA/PVP Blend. Br. J. Appl. Sci. Technol. 4(30), 4263–4279 (2014).
CASGoogle Scholar
53. Leyva-Gómez G, Santillan-Reyes E, Lima E et al. A novel hydrogel of poloxamer 407 and chitosan obtained by gamma irradiation exhibits physicochemical properties for wound management. Mater. Sci. Eng. C. 74, 36–46 (2017).
Medline CASGoogle Scholar
54. Herculano RD, Alencar De Queiroz AA, Kinoshita A, Oliveira ON, Graeff CFO. On the release of metronidazole from natural rubber latex membranes. Mater. Sci. Eng. C. 31(2), 272–275 (2011).
CASGoogle Scholar
55. Bharti K, Mittal P, Mishra B. Formulation and characterization of fast dissolving oral films containing buspirone hydrochloride nanoparticles using design of experiment. J. Drug Deliv. Sci. Technol. 49(December 2018), 420–432 (2019).
CASGoogle Scholar
56. Chonkar AD, Rao JV, Managuli RS et al. Development of fast dissolving oral films containing lercanidipine HCl nanoparticles in semicrystalline polymeric matrix for enhanced dissolution and ex vivo permeation. Eur. J. Pharm. Biopharm. 103, 179–191 (2016).
Medline CASGoogle Scholar
57. de Alcantara Sica de Toledo L, Rosseto HC, Ravani L, Cortesi R, Luciano Bruschi M. Waste material of propolis as a film forming agent intended to modify the metronidazole release: preparation and characterization. Curr. Drug Deliv. 13(7), 1152–1164 (2016). • Characterization of pharmaceutical films containing metronidazole.
MedlineGoogle Scholar
58. Aider M. Chitosan application for active bio-based films production and potential in the food industry: review. LWT-Food Sci. Technol. 43(6), 837–842 (2010).
CASGoogle Scholar
59. Bodini RB, Guimarães J das GL, Monaco-Lourenço CA, Aparecida de Carvalho R. Effect of starch and hydroxypropyl methylcellulose polymers on the properties of orally disintegrating films. J. Drug Deliv. Sci. Technol. 51(November 2018), 403–410 (2019).
CASGoogle Scholar
60. Moreno MF. Application of small punch testing on the mechanical and microstructural characterizations of P91 steel at room temperature. Int. J. Press. Vessel. Pip. 142–143, 1–9 (2016).
CASGoogle Scholar
61. Materials and processes in manufacturing. 9th Edition, Degarmo EPKohser RAKlamecki BE (Eds.) Wiley & Sons, NY, USA, 1154 (2003).
Google Scholar
62. Kamper SL, Fennema O. Water vapor permeability of an edible, fatty acid, bilayer film. J. Food Sci. 49(6), 1482–1485 (1984).
CASGoogle Scholar
63. Biquet B, Labuza TP. Evaluation of the moisture permeability characteristics of chocolate films as an edible moisture barrier. J. Food Sci. 53(4), 989–998 (1988).
Google Scholar
64. Bassi da Silva J, Ferreira SB de S, de Freitas O, Bruschi ML. A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems. Drug Dev. Ind. Pharm. 43(7), 1053–1070 (2017).
MedlineGoogle Scholar
65. Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv. Drug Deliv. Rev. 57(11), 1556–1568 (2005).
Medline CASGoogle Scholar
66. Validation of Analytical Procedures: Text and Methodology Q2(R1). In: ICH (2005). www.ema.europa.eu/en/ich-q2-r1-validation-analytical-procedures-text-methodology
Google Scholar
67. Pereira RR de A, Godoy JSR, Svidzinski TIE, Bruschi ML. Preparation and characterization of mucoadhesive thermoresponsive systems containing propolis for the treatment of vulvovaginal candidiasis. J. Pharmaeutical Sci. 102(4), 1222–1234 (2013).
Medline CASGoogle Scholar

Vol. 11, No. 7

Metrics

Downloaded 210 times

History

Received 25 March 2020

Accepted 17 June 2020

Published online 5 July 2020

Published in print July 2020

Information

Keywords

Author contributions

CF Vecchi contributed to conceptualization, methodology, investigation, formal analysis and writing original draft preparation. RS dos Santos contributed to investigation, methodology and formal analysis. ML Bruschi contributed to conceptualization, methodology, resources, writing-reviewing and editing, supervision, project administration and funding acquisition.

Acknowledgments

The authors are thankful to CNPq, CAPES and FINEP (Brazilian Financier of Studies and Projects).

Financial & competing interests disclosure

CF Vecchi was supported by MD scholarship from the Brazilian National Research Council CNPq. RS dos Santos was supported by MD scholarship from the Brazilian Coordination for the Improvement of Higher Education CAPES (Grant code – 001). ML Bruschi received grant from the Brazilian National Research Council CNPq (Process n° 307442/2017-9). The authors declare no conflict of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download