AAPS PharmSciTech

, Volume 15, Issue 4, pp 1021–1028 | Cite as

Comparative Study to Investigate the Effect of Meloxicam or Minocycline HCl In Situ Gel System on Local Treatment of Periodontal Pockets

  • Abeer Ahmed Kassem
  • Fatma Ahmed Ismail
  • Vivian Fahim Naggar
  • Elsayed Aboulmagd
Research Article

Abstract

In situ gelling formulations allow easy application to the target area. Gelation is induced by physiological stimuli at the site of application where the formula attains semisolid properties and exerts sustained drug release. In situ gelling formulations containing either 3% meloxicam (Mx) or 2% minocycline HCl (MH) were prepared for local application into the periodontal pockets. Gel formulations were based on the thermosensitive Pluronic® (Pl) and the pH-sensitive Carbopol® (C) polymers. C gels were prepared in combination with HPMC (H) to decrease its acidity. The total percent drug released from Pl formulae was 21.72% after 1 week for Mx and 85% after 3 days for MH. Their release kinetics data indicated anomalous non-Fickian behavior that could be controlled by both diffusion and chain relaxation. Addition of MH to C/H gels (1:2.5) resulted in liquefaction, followed by drug precipitation. Regarding C/H gel containing Mx, it showed a prolonged release rate up to 7 days with an initial burst effect; the kinetics data revealed Fickian-diffusion mechanism. The in vitro antibacterial activity studies for MH gel in Pl revealed that the drug released exceeded the minimum inhibitory concentration (MIC) of MH against Staphylococcus aureus ATCC 6538; placebo gel showed no effect on the microorganism. Clinical evaluation of Pl gels containing either Mx or MH showed significant improvement in chronic periodontitis patients, manifested by decrease in pocket depth and gingival index and increase in bone density.

KEY WORDS

antiinflammatory antimicrobial Carbopol® clinical evaluation periodontitis pH-sensitive Pluronic® thermosensitive 

Notes

Acknowledgments

Special thanks to the staff members of the Department of Periodontology, Oral Medicine, Oral diagnosis and Radiology, Faculty of Dentistry, Alexandria University, Egypt: Prof. Dr. Maha A. Abu-Khedr, Prof. Dr. Sabah A. Mahmoud, Prof. Dr. Shahira A. El-Domiaty and Dentist Nevine A. Abo El Khair, for their valuable effort in the clinical evaluation of the selected formulae in this research.

Conflict of Interest

This manuscript has not been published and is not under consideration for publication elsewhere, and we have no conflict of interest to disclose.

References

  1. 1.
    Mundargi RC, Srirangarajan S, Agnihotri SA, Patil SA, Ravindra S, Setty SB, et al. Development and evaluation of novel biodegradable microspheres based on poly (d, l-lactide- co-glycolide) and poly (ε-caprolactone) for controlled delivery of doxycycline in the treatment of human periodontal pocket: in vitro and in vivo studies. J Control Release. 2007;119:59–68.PubMedCrossRefGoogle Scholar
  2. 2.
    Salvi G, Lang N. The effects of non-steroidal anti-inflammatory drugs (selective and non-selective) on the treatment of periodontal diseases. Curr Pharm Des. 2005;11:1757–69.PubMedCrossRefGoogle Scholar
  3. 3.
    Engelhardt G. Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2. Br J Rheumatol. 1996;35:4–12.PubMedCrossRefGoogle Scholar
  4. 4.
    Tschoppe P, Kielbassa AM. The role of COX-2 in dentistry. Past or future? Schweiz Monatsschr Zahnmed. 2006;116:880–6.PubMedGoogle Scholar
  5. 5.
    Bezerra MM, de Lima V, Alencar VB, Vieira IB, Brito GA, Ribeiro RA, et al. Selective cyclooxygenase-2 inhibition prevents alveolar bone loss in experimental periodontitis in rats. J Periodontol. 2000;71:1009–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Buduneli N, Vardar S, Atilla G, Sorsa T, Luoto H, Baylas H. Gingival crevicular fluid matrix metalloproteinase-8 levels following adjunctive use of meloxicam and initial phase of periodontal therapy. J Periodontol. 2002;73:103–9.PubMedCrossRefGoogle Scholar
  7. 7.
    De Oliveira LF, Jorge AO, Dos Santos SS. In vitro minocycline activity on superinfecting microorganisms isolated from chronic periodontitis patients. Braz Oral Res. 2006;20:202–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Seymour RA, Heasman PA. Tetracyclines in the management of periodontal diseases. A review. J Clin Periodontol. 1995;22:22–35.PubMedCrossRefGoogle Scholar
  9. 9.
    Panwar M, Gupta S. Local drug delivery with tetracycline fiber: an alternative to surgical periodontal therapy. Med J Armed Forces India. 2009;65:244–6.CrossRefGoogle Scholar
  10. 10.
    De Souza Ferreira SB, De Assis Dias BR, Obregon CS, Gomes CC, De Araujo Pereira RR, Ribeiro Godoy JS, et al. Microparticles containing propolis and metronidazole: in vitro characterization, release study and antimicrobial activity against periodontal pathogens. Pharm Dev Technol. 2014;19:173–80.Google Scholar
  11. 11.
    Vyas SP, Sihorkar V, Mishra V. Controlled and targeted drug delivery strategies towards intraperiodontal pocket diseases. J Clin Pharm Ther. 2000;25:21–42.PubMedCrossRefGoogle Scholar
  12. 12.
    Soppimath KS, Aminabhavi TM, Dave AM, Kumbar SG, Rudzinski WE. Stimulus-responsive “smart” hydrogels as novel drug delivery systems. Drug Dev Ind Pharm. 2002;28:957–74.PubMedCrossRefGoogle Scholar
  13. 13.
    Singh RM, Kumar A, Pathak K. Mucoadhesive in situ nasal gelling drug delivery systems for modulated drug delivery. Expert Opin Drug Deliv. 2013;10:115–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Dabhi MR, Sheth NR. Formulation development of physiological environment responsive periodontal drug delivery system for local delivery of metronidazole benzoate. Drug Dev Ind Pharm. 2013;39:425–36.PubMedCrossRefGoogle Scholar
  15. 15.
    Shin BK, Baek EJ, Choi SG, Davaa E, Nho YC, Lim YM, et al. Preparation and irradiation of Pluronic F127-based thermoreversible and mucoadhesive hydrogel for local delivery of naproxen. Drug Dev Ind Pharm. 2013;39:1874–80.Google Scholar
  16. 16.
    Radivojša M, Grabnar I, Grabnar PA. Thermoreversible in situ gelling poloxamer-based systems with chitosan nanocomplexes for prolonged subcutaneous delivery of heparin: design and in vitro evaluation. Eur J Pharm Sci. 2013;50:93–101.PubMedCrossRefGoogle Scholar
  17. 17.
    Çetin E, Buduneli N, Atlıhan E, Kırılmaz L. In vitro studies of a degradable device for controlled-release of meloxicam. J Clin Periodontol. 2005;32:773–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Çetin E, Buduneli N, Atlihan E, Kirilmaz L. In vitro studies on controlled-release cellulose acetate films for local delivery of chlorhexidine, indomethacin, and meloxicam. J Clin Periodontol. 2004;31:1117–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Graca MA, Watts TLP, Wilson RF, Palmer RM. A randomized controlled trial of a 2% minocycline gel as an adjunct to non-surgical periodontal treatment, using a design with multiple matching criteria. J Clin Periodontol. 1997;24:249–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Schmolka IR. Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res. 1972;6:571–82.PubMedCrossRefGoogle Scholar
  21. 21.
    Ismail FA. Formulation and in vitro evaluation of injectable periodontal gel formulae containing Doxycycline Hyclate. Alex J Pharm Sci. 2006;20:145–50.Google Scholar
  22. 22.
    Kumar S, Himmelstein KJ. Modification of in situ gelling behavior of carbopol solutions by hydroxypropyl methylcellulose. J Pharm Sci. 1995;84:344–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Ismail FA, Napaporn J, Hughes JA, Brazeau GA. In situ gel formulations for gene delivery: release and myotoxicity studies. Pharm Dev Technol. 2000;5:391–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Deasy PB, Collins AE, MacCarthy DJ, Russell RJ. Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. J Pharm Pharmacol. 1989;41:694–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Ambrus R, Kocbek P, Kristl J, Šibanc R, Rajkó R, Szabó-Révész P. Investigation of preparation parameters to improve the dissolution of poorly water-soluble meloxicam. Int J Pharm. 2009;381:153–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Keny R, Mankame S, Lourenco C. Formulation and evaluation of once daily minocycline hydrochloride extended release matrix tablets. Indian J Pharm Sci. 2009;71:295.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–1.PubMedGoogle Scholar
  28. 28.
    Ahmed M, El-Gibaly I, Ahmed S. Effect of cyclodextrins on the physicochemical properties and antimycotic activity of clotrimazole. Int J Pharm. 1998;171:111–21.CrossRefGoogle Scholar
  29. 29.
    Agarwal RK, Robinson DH, Maze GI, Reinhardt RA. Development and characterization of tetracycline-poly (lactide/glycolide) films for the treatment of periodontitis. J Control Release. 1993;23:137–46.CrossRefGoogle Scholar
  30. 30.
    Loe H. The gingival index, the plaque index and the retention index systems. J Periodontol. 1967;38:610–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Braegger U, Pasquali L, Weber H, Kornman KS. Computer-assisted densitometric image analysis (CADIA) for the assessment of alveolar bone density changes in furcations. J Clin Periodontol. 1989;16:46–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Yang M, Lai SK, Wang YY, Zhong W, Happe C, Zhang M, et al. Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus. Angew Chem Int Ed. 2011;50:2597–600.CrossRefGoogle Scholar
  33. 33.
    Esposito E, Carotta V, Scabbia A, Trombelli L, D’ Antona P, Menegatti E, et al. Comparative analysis of tetracycline-containing dental gels: poloxamer- and monoglyceride-based formulations. Int J Pharm. 1996;142:9–23.CrossRefGoogle Scholar
  34. 34.
    Zhang L, Parsons DL, Navarre C, Kompella UB. Development and in vitro evaluation of sustained release poloxamer 407 (P407) gel formulations of ceftiofur. J Control Release. 2002;85:73–81.PubMedCrossRefGoogle Scholar
  35. 35.
    Barreiro-Iglesias R, Bromberg L, Temchenko M, Hatton TA, Concheiro A, Alvarez-Lorenzo C. Solubilization and stabilization of camptothecin in micellar solutions of pluronic-g-poly (acrylic acid) copolymers. J Control Release. 2004;97:537–49.PubMedCrossRefGoogle Scholar
  36. 36.
    Sweetman SC. Martindale: the complete drug reference. 34th ed. London: The Pharmaceutical press; 2005.Google Scholar
  37. 37.
    Ponchel G, Touchard F, Duchene D, Peppas NA. Bioadhesive analysis of controlled release systems. I. Fracture and interpenetration analysis in PAA-containing systems. J Control Release. 1987;5:129–41.CrossRefGoogle Scholar
  38. 38.
    Moore T, Croy S, Mallapragada S, Pandit N. Experimental investigation and mathematical modeling of Pluronic F127 gel dissolution: drug release in stirred systems. J Control Release. 2000;67:191–202.PubMedCrossRefGoogle Scholar
  39. 39.
    Baun DC, Walker GC. The prolonged release of caramiphen hydrochloride and atropine sulfate from compressed tablets containing Carbopol 934. Pharm Acta Helv. 1971;46:94–113.PubMedGoogle Scholar
  40. 40.
    Durrani MJ, Andrews A, Whitaker R, Benner SC. Studies on drug release kinetics from carbomer matrices. Drug Dev Ind Pharm. 1994;20:2439–47.CrossRefGoogle Scholar
  41. 41.
    Nassar CA, Nassar PO, Nassar PM, Spolidorio LC. Selective cyclooxygenase-2 inhibition prevents bone resorption. Braz Oral Res. 2005;19:36–40.PubMedCrossRefGoogle Scholar
  42. 42.
    Vardar S, Baylas H, Huseyinov A. Effects of selective cyclooxygenase-2 inhibition on gingival tissue levels of prostaglandin E2 and prostaglandin F2alpha and clinical parameters of chronic periodontitis. J Periodontol. 2003;74:57–63.PubMedCrossRefGoogle Scholar
  43. 43.
    Lu HK, Chei CJ. Efficacy of subgingivally applied minocycline in the treatment of chronic periodontitis. J Periodontal Res. 2005;40:20–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Meinberg TA, Barnes CM, Dunning DG, Reinhardt RA. Comparison of conventional periodontal maintenance versus scaling and root planing with subgingival minocycline. J Periodontol. 2002;73:167–72.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Abeer Ahmed Kassem
    • 1
    • 3
  • Fatma Ahmed Ismail
    • 1
  • Vivian Fahim Naggar
    • 1
  • Elsayed Aboulmagd
    • 2
  1. 1.Department of Pharmaceutics, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt
  2. 2.Department of Microbiology, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt
  3. 3.Department of Pharmaceutics, Faculty of Pharmacy and Drug ManufacturingPharos University in AlexandriaAlexandriaEgypt

Personalised recommendations