AAPS PharmSciTech

, Volume 7, Issue 3, pp E162–E171 | Cite as

Development of tetracycline-serratiopeptidase-containing periodontal gel: Formulation and preliminary clinical study

  • Manish Maheshwari
  • Gunjan Miglani
  • Amita Mali
  • Anant Paradkar
  • Shigeo Yamamura
  • Shivajirao Kadam


The purpose of this research was to reduce the polymer concentration and to obtain reasonable viscosity at a lower concentration of pluronic by the addition of a viscosity modifier. A 20% wt/wt pluronic gel was prepared on a weight basis using the cold method. The effect of the amount of tetracycline and Aerosil on gel properties was studied. The gel was evaluated using different parameters: polarizing microscopy, gelation, gel melting, bioadhesivity, viscosity, drug release, and stability of enzyme. An in vivo study was performed to evaluate the clinical efficiency of the liquid crystalline gel. Addition of Aerosil to the gel favored hexagonal phase formation. Viscosity and bioadhesivity increased with an increase in the concentration of Aerosil. Release of tetracycline was sustained as the concentration of Aerosil increased. Various clinical parameters confirmed the acceptability and efficiency of this gel system.


periodontitis pluronic Aerosil serratiopeptidase clinical study 


  1. 1.
    Veyries ML, Courraze G, Geiger S, et al. Controlled release of vancomycin from poloxamer 407 gels.Int J Pharm. 1999;192: 183–193.CrossRefPubMedGoogle Scholar
  2. 2.
    Paavola A, Kilpelaine I, Yliruusi J, Rosenberg P. Controlled release injectable liposomal gel of ibuprofen for epidural analgesia.Int J Pharm. 2000;199:85–93.CrossRefPubMedGoogle Scholar
  3. 3.
    Kim SY, Ha JC, Lee M. Poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide)/poly (caprolactone) amphiphilic block copolymer nanospheres, II: thermoresponsive behavior.J Control Release. 2000;65:345–358.CrossRefPubMedGoogle Scholar
  4. 4.
    Ricci EJ, Lunardi L, Nanclares DMA, Marchetti JM. Sustained release of lidocaine from Poloxamer 407 gels.Int J Pharm. 2005; 288:235–244.CrossRefPubMedGoogle Scholar
  5. 5.
    Pisal SS, Parakar AR, Mahadik KR, Kadam SS. Pluronic gels for nasal delivery of Vitamin B12, Part I: preformulation study.Int J Pharm. 2004;270:37–45.CrossRefPubMedGoogle Scholar
  6. 6.
    Pandit N, Trygstad T, Croy S, Bohorquez M, Kock C. Effect of salt on micellization, clouding and solubilization behavior of pluronic F127 solutions.J Colloid Interface Sci. 2000;222:213–220.CrossRefPubMedGoogle Scholar
  7. 7.
    El-Kamel AH. In vitro and in vivo evaluation of pluronic F127 based ocular delivery system for timolol maleate.Int J Pharm. 2002; 241:47–55.CrossRefPubMedGoogle Scholar
  8. 8.
    Lin H, Sung KC. Carbopol/pluronic phase change solution for ophthalmic drug delivery.J Control Release. 2000;69:379–388.CrossRefPubMedGoogle Scholar
  9. 9.
    Raghavan SR, Walls HJ, Khan SA. Rheology of silica dispersions in organic liquids: new evidence for solvation forces dictated by hydrogen bonding.Langmuir. 2000;16:7920–7930.CrossRefGoogle Scholar
  10. 10.
    Shah MH, Paradkar A. Cubic liquid crystalline glyceryl monooleate matrices for oral delivery of enzyme.Int J Pharm. 2005;294:161–171.CrossRefPubMedGoogle Scholar
  11. 11.
    Adriaens PA, Edwards CA, De-Boever JA, Loesche WJ. Ultrastructural observation on bacterial invasion in cementum and radicular dentin of periodontally diseased human teeth.J Periodontol. 1988;59:493–503.CrossRefPubMedGoogle Scholar
  12. 12.
    Noyan U, Yilmaz S, Kuru B, Kadir T, Acar O, Buget EA. Clinical and microbiological evaluation of systemic and local metronidazole delivery in adult periodontitis patients.J Clin Periodontol. 1997; 24:158–165.CrossRefPubMedGoogle Scholar
  13. 13.
    Medlicott NJ, Rathbone MJ, Tucker IG, Hol-Borow DW. Delivery systems for the administration of drugs to the periodontal pocket.Adv Drug Deliv Rev. 1994;13:181–203.CrossRefGoogle Scholar
  14. 14.
    Stoltze K, Stellfeld M. Systemic absorption of metronidazole after application of a metronidazole 25% dental gel.J Clin Periodontol. 1992;19:693–697.CrossRefPubMedGoogle Scholar
  15. 15.
    Goodson JM, Holborow D, Dunn RL, Hogan P, Dunham S. Monolithic tetracycline-containing fibers for controlled delivery to periodontal pockets.J Periodontol. 1983;54:575–579.CrossRefPubMedGoogle Scholar
  16. 16.
    Killoy WJ. The use of locally delivered chlorhexidine in the treatment of periodontitis: clinical results.J Clin Periodontol. 1998;25:953–958.CrossRefPubMedGoogle Scholar
  17. 17.
    Norling T, Lading P, Engstrom S, Larsson K, Nissen SS. Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease.J Clin Periodontol. 1992;19:687–692.CrossRefPubMedGoogle Scholar
  18. 18.
    Mazzone A, Catalan M, Costanzo M, et al. Evaluation of serratiopeptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double blind, randomized trial versus placebo.J Int Med Res. 1990;18:379–388.CrossRefPubMedGoogle Scholar
  19. 19.
    Malmsten M, Lindman B. Self-assembly in aqueous block copolymer solutions.Macromolecules 1992;25:5440–5445.CrossRefGoogle 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;6:571–582.CrossRefPubMedGoogle Scholar
  21. 21.
    Rosevear FB. The microscopy of the liquid crystalline neat and middle phases of soaps and synthetic detergents.J Am Oil Chem Soc. 1954;13:628–638.CrossRefGoogle Scholar
  22. 22.
    Miller SC, Donovan MD. Effect of poloxamer 407 gel on the miotic activity of pilocarpine nitrate in rabbits.Int J Pharm. 1982;12:147–152.CrossRefGoogle Scholar
  23. 23.
    Nielsen LS, Schubert L, Hansen J. Bioadhesive drug delivery system, I: characterization of mucoadhesive properties of systems based on glyceryl monooleate and glyceryl monolinoleate.Eur J Pharm Sci. 1998;6:231–239.CrossRefPubMedGoogle Scholar
  24. 24.
    Korsmeyer RW, Gurny R, Doelker EM, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers.Int J Pharm. 1983;15:25–35.CrossRefGoogle Scholar
  25. 25.
    Institute of Medicine.Food Chemical Codex. 5th ed. Washington, DC: National Academies Press 2003:495–496.Google Scholar
  26. 26.
    Turesky S, Gilmore ND, Glickman I. Reduced plaque formation by the chloromethyl analogue of vitamin C.J Periodontol. 1970;41:41–43.CrossRefPubMedGoogle Scholar
  27. 27.
    Loee H, Silness J. Periodontal disease in pregnancy.Acta Odontol Scand. 1963;21:533–542.CrossRefGoogle Scholar
  28. 28.
    Muhlemann HR, Son S. Gingival sulcus bleeding—a leading symptom in initial gingivitis.Helv Odontol Acta. 1971;15:107–113.PubMedGoogle Scholar
  29. 29.
    Clark DC, Quee TC, Bergeron MJ. Reliability of attachment level measurements using the cementoenamel junction and plastic stent.J Periodontol. 1987;58:115–118.CrossRefPubMedGoogle Scholar
  30. 30.
    Ivanova R, Lindman B, Alexandris P. Effect of pharmaceutically acceptable glycols on the stability of the liquid crystalline gels formed by poloxamer 407 in water.J Colloid Interface Sci. 2002;252:226–235.CrossRefPubMedGoogle Scholar
  31. 31.
    Wanka G, Hoffmann H, Ulbricht V. Phase diagrams and aggregation behavior of poly (oxyethylene)-poly (oxypropylene)-poly (oxyethylene) triblock copolymers in aqueous solution.Macromolecules. 1994; 27:4145–4159.CrossRefGoogle Scholar
  32. 32.
    Cabana A, Ait-kadi A, Juhasz J. Study of the gelation process of polyethylene oxide-polypropylene oxide-polyethylene oxide copolymer (poloxamer 407) aqueous solution.J Colloid Interface Sci. 1997; 190:307–312.CrossRefPubMedGoogle Scholar
  33. 33.
    Song MJ, Lee DS, Ahn JH, Kim DJ, Kim SC. Dielectric behavior during sol-gel transition of PEO-PPO-PEO triblock copolymer aqueous solution.Polymer Bulletin. 2000;43:497–504.CrossRefGoogle Scholar
  34. 34.
    Bohorquez M, Kock C, Tryastad T, Pandit N. A study of the temperature-dependent micellization of pluronic F127.J Colloid Interface Sci. 1999;216:34–40.CrossRefPubMedGoogle Scholar
  35. 35.
    Esposito E, Carotta V, Scabbia A, et al. Comparative analysis of tetracycline-containing dental gels: poloxamer- and monoglyceride-based formulations.Int J Pharm. 1996;142:9–23.CrossRefGoogle Scholar
  36. 36.
    Shah JC, Sadhale Y, Chilukuri DM. Cubic phase gels as drug delivery systems.Adv Drug Deliv Rev. 2001;47:229–250.CrossRefPubMedGoogle Scholar
  37. 37.
    Stratton LP, Dong A, Manning MC, Carpenter JF. Drug delivery matrix containing native protein precipitate suspended in poloxamer gel.J Pharm Sci. 1997;86:1006–1010.CrossRefPubMedGoogle Scholar
  38. 38.
    Heijl L, Dahlen V, Sundin Y. A 4-quadrant comparative study of periodontal treatment using tetracycline-containing drug delivery fibers and scaling.J Clin Periodontol. 1991;18:111–116.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2006

Authors and Affiliations

  • Manish Maheshwari
    • 1
  • Gunjan Miglani
    • 2
  • Amita Mali
    • 2
  • Anant Paradkar
    • 1
  • Shigeo Yamamura
    • 3
  • Shivajirao Kadam
    • 1
  1. 1.Department of Pharmaceutics, Poona College of PharmacyBharati Vidyapeeth Deemed UniversityPuneIndia
  2. 2.Department of Periodontology, Dental College and HospitalBharati Vidyapeeth Deemed UniversityPuneIndia
  3. 3.School of Pharmaceutical SciencesToho UniversityFunabashi, ChibaJapan

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