PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2007 September; 8(3): E184–E194.
Published online 2007 September 14. doi:  10.1208/pt0803075
PMCID: PMC2750571

Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases

Abstract

The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(ε-caprolactone) (CH/PCL) films and chitosan films were prepared. thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1[ratio]0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1[ratio]1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1[ratio]0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 μg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained.

Keywords: Metronidazole benzoate, chitosan, poly(ε-caprolactone), periodontal, mucoadhesive, correlation

Full Text

The Full Text of this article is available as a PDF (438K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Piovano S. Bacteriology of most frequent oral anaerobic infections. Anaerobe. 1999;5:221–227. doi: 10.1006/anae.1999.0204. [Cross Ref]
2. Perioli L, Ambrogi V, Rubini D, et al. Novel mucoadhesive buccal formulation containing metronidazole for the treatment of periodontal disease. J Control Release. 2004;95:521–533. doi: 10.1016/j.jconrel.2003.12.018. [PubMed] [Cross Ref]
3. Schwach-Abdellaoui K, Vivien-Castioni N, Gurny R. Local delivery of antimicrobial agents for the treatment of periodontal diseases. Eur J Pharm Biopharm. 2000;50:83–99. doi: 10.1016/S0939-6411(00)00086-2. [PubMed] [Cross Ref]
4. Vyas SP, Sihorkar V, Mishra V. Controlled and targeted drug delivery strategies towards intraperiodontal pocket diseases. J Clin Pharm Ther. 2000;25:21–42. doi: 10.1046/j.1365-2710.2000.00261.x. [PubMed] [Cross Ref]
5. Brackett MG, Drisko CL, Thompson AL, Waller JL, Marshall DL, Schuster GS. Penetration of fluids into periodontal pockets using a powered toothbrush/irrigator device. J Contemp Dent Pract. 2006;7:30–39. [PubMed]
6. Ahuja A, Ali J, Rahman S. Biodegradable periodontal intrapocket device containing metronidazole and amoxycillin: formulation and characterisation. Pharmazie. 2006;61:25–29. [PubMed]
7. Barat R, Srinatha A, Pandit JK, et al. Niridazole biodegradable inserts for local long-term treatment of periodontitis: possible new life for an orphan drug. Drug Deliv. 2006;13:365–373. doi: 10.1080/10717540500398126. [PubMed] [Cross Ref]
8. Samati Y, Yuksel N, Tarimci N. Preparation and characterization of poly (D L-lactic-co-glycolic acid) microspheres containing flurbiprofen sodium. Drug Deliv. 2006;13:105–111. doi: 10.1080/10717540500313331. [PubMed] [Cross Ref]
9. Liebana J, Castillo AM, Alvarez M. Periodontal diseases: microbiological considerations. Med Oral Patol Oral Cir Bucal. 2004;9:82–91. [PubMed]
10. Zheng LY, Zhu JF. Study on antimicrobial activity of chitosan with different molecular weights. Carbohydr Polym. 2003;54:527–530. doi: 10.1016/j.carbpol.2003.07.009. [Cross Ref]
11. Perugini P, Genta I, Conti B, Modena T, Pavanetto F. Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug. Int J Pharm. 2003;252:1–9. doi: 10.1016/S0378-5173(02)00602-6. [PubMed] [Cross Ref]
12. USP.US Pharmacopeia National Formulary. vol. 21. Rockville, MD: USP; 1999.
13. Patty PJ, Frisken BJ. Direct determination of the number-weighted mean radius and polydispersity from dynamic light-scattering data. Appl Opt. 2006;45:2209–2216. doi: 10.1364/AO.45.002209. [PubMed] [Cross Ref]
14. Peh KK, Wong CF. Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties. J Pharm Pharm Sci. 1999;2:53–61. [PubMed]
15. Baro M, Sanchez E, Delgado A, Perera A, Evora C. In vitro-in vivo characterization of gentamicin bone implants. J Control Release. 2002;83:353–364. doi: 10.1016/S0168-3659(02)00179-7. [PubMed] [Cross Ref]
16. Ponchel G, Touchard F, Duchene D, Peppas NA. Bioadhesive analysis of controlled-release systems, I: fracture and interpenetration analysis in poly(acrylic acid)-containing systems. J Control Release. 1987;5:129–141. doi: 10.1016/0168-3659(87)90004-6. [Cross Ref]
17. Wong CF, Yuen KH, Peh KK. Formulation and evaluation of controlled release Eudragit buccal patches. Int J Pharm. 1999;178:11–22. doi: 10.1016/S0378-5173(98)00342-1. [PubMed] [Cross Ref]
18. Padula CP, Colombo G, Nicoli S, Catellani PL, Massimo G, Santi P. Bioadhesive film for the transdermal delivery of lidocaine: in vitro and in vivo behavior. J Control Release. 2003;88:277–285. doi: 10.1016/S0168-3659(03)00015-4. [PubMed] [Cross Ref]
19. Ritger PL, Peppas NA. A simple equation for description of solute release, II: Fickian and anomalous release from swellable devices. J Control Release. 1987;5:37–42. doi: 10.1016/0168-3659(87)90035-6. [Cross Ref]
20. Metz P, Kohlhepp SJ, Gilbert DN. Study of different off-line sample processing procedures and the measurement of antibiotic and antiviral levels in human serum by high-performance liquid chromatography. J Chromatogr B. 2002;773:159–166. doi: 10.1016/S1570-0232(02)00140-X. [PubMed] [Cross Ref]
21. Sarasam A, Madihally SV. Characterization of chitosanpolycaprolactone blends for tissue engineering applications. Biomaterials. 2005;26:5500–5508. doi: 10.1016/j.biomaterials.2005.01.071. [PubMed] [Cross Ref]
22. Roldo M, Hornof M, Caliceti P, Bernkop-Schnurch A. Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation. Eur J Pharm Biopharm. 2004;57:115–121. doi: 10.1016/S0939-6411(03)00157-7. [PubMed] [Cross Ref]
23. Wenling C, Duohui J, Jiamou L, Yandao G, Nanming Z, Xiufang Z. Effects of the degree of deacetylation on the physicochemical properties and Schwann cell affinity of chitosan films. J Biomater Appl. 2005;20:157–177. doi: 10.1177/0885328205049897. [PubMed] [Cross Ref]
24. Needleman IG, Smales FC. In vitro assessment of bioadhesion for periodontal and buccal drug delivery. Biomaterials. 1995;16:617–624. doi: 10.1016/0142-9612(95)93859-C. [PubMed] [Cross Ref]
25. Harding SE. Trends in mucoadhesive analysis. Trends Food Sci Tech. 2006;17:255–262. doi: 10.1016/j.tifs.2005.12.007. [Cross Ref]
26. Ikinci G, Senel S, Akincibay H, et al. Effect of chitosan on a periodontal pathogen Porphyromonas gingivalis. Int J Pharm. 2002;235:121–127. doi: 10.1016/S0378-5173(01)00974-7. [PubMed] [Cross Ref]
27. Dhanikula AB, Panchagnula R. Development and characterization of biodegradable chitosan films for local delivery of paclitaxel. AAPS J. 2004;6:27–27. doi: 10.1208/aapsj060327. [PMC free article] [PubMed] [Cross Ref]
28. Martin AN, editor. Polymer science. 4th ed. Philadelphia, PA: Lea & Febiger; 1993. pp. 575–578.
29. Lorenzo-Lamosa ML, Remunan-Lopez C, Vila-Jato JL, Alonso MJ. Design of microencapsulated chitosan microspheres for colonic drug delivery. J Control Release. 1998;52:109–118. doi: 10.1016/S0168-3659(97)00203-4. [PubMed] [Cross Ref]
30. Sarasam AR, Krishnaswamy RK, Madihally SV. Blending chitosan with polyoaprolactone: effects on physicochemical and antibacterial properties. Biomacromolecules. 2006;7:1131–1138. doi: 10.1021/bm050935d. [PubMed] [Cross Ref]
31. Colombo P, Santi P, Bettini R, Brazel CS. Drug release from swelling controlled systems. In: Wise DL, editor. Handbook of Pharmaceutical Controlled Release Technology. New York, NY: Marcel Dekker; 2000. pp. 183–209.
32. Khanna R, Agarwal SP, Ahuja A. Mucoadhesive buccal tablets of cłotimazole for oral candidiasis. Drug Dev Ind Pharm. 1997;23:1–7. doi: 10.3109/03639049709150554. [Cross Ref]
33. Mody SSB, Mody PD, Doshi MM, inventors. Pharmaceutical dental formulation for topical application of metronidazole benzoate and chlorhexidine gluconate. US patent 6 017 516. January 25, 2000.
34. Parfitt K. Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press; 1999.
35. Milazzo I, Blandino G, Musumeci R, Nicoletti G, Lo Bue AM, Speciale A. Antibacterial activity of moxifloxacin against periodontal anaerobic pathogens involved in systemic infections. Int J Antimicrob Agent. 2002;20:451–456. doi: 10.1016/S0924-8579(02)00190-5. [PubMed] [Cross Ref]
36. Mckellar QA, Sanchez Bruni SF, Jones DG. Pharmacokinetic/pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine. J Vet Pharmacol Ther. 2004;27:503–514. doi: 10.1111/j.1365-2885.2004.00603.x. [PubMed] [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists