Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2006 September; 7(3): E162–E171.
Published online 2006 September 15. doi:  10.1208/pt070376
PMCID: PMC2750518

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


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.

Keywords: periodontitis, pluronic, Aerosil, serratiopeptidase, clinical study

Full Text

The Full Text of this article is available as a PDF (439K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Veyries ML, Courraze G, Geiger S, et al. Controlled release of vancomycin from poloxamer 407 gels. Int J Pharm. 1999;192:183–193. doi: 10.1016/S0378-5173(99)00307-5. [PubMed] [Cross Ref]
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. doi: 10.1016/S0378-5173(00)00376-8. [PubMed] [Cross Ref]
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. doi: 10.1016/S0168-3659(99)00207-2. [PubMed] [Cross Ref]
4. Ricci EJ, Lunardi L, Nanclares DMA, Marchetti JM. Sustained release of lidocaine from Poloxamer 407 gels. Int J Pharm. 2005;288:235–244. doi: 10.1016/j.ijpharm.2004.09.028. [PubMed] [Cross Ref]
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. doi: 10.1016/j.ijpharm.2003.10.005. [PubMed] [Cross Ref]
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. doi: 10.1006/jcis.1999.6628. [PubMed] [Cross Ref]
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. doi: 10.1016/S0378-5173(02)00234-X. [PubMed] [Cross Ref]
8. Lin H, Sung KC. Carbopol/pluronic phase change solution for ophthalmic drug delivery. J Control Release. 2000;69:379–388. doi: 10.1016/S0168-3659(00)00329-1. [PubMed] [Cross Ref]
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. doi: 10.1021/la991548q. [Cross Ref]
10. Shah MH, Paradkar A. Cubic liquid crystalline glyceryl monooleate matrices for oral delivery of enzyme. Int J Pharm. 2005;294:161–171. doi: 10.1016/j.ijpharm.2005.01.019. [PubMed] [Cross Ref]
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. [PubMed]
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. doi: 10.1111/j.1600-051X.1997.tb00485.x. [PubMed] [Cross Ref]
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. doi: 10.1016/0169-409X(94)90033-7. [Cross Ref]
14. Stoltze K, Stellfeld M. Systemic absorption of metronidazole after application of a metronidazole 25% dental gel. J Clin Periodontol. 1992;19:693–697. [PubMed]
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. [PubMed]
16. Killoy WJ. The use of locally delivered chlorhexidine in the treatment of periodontitis: clinical results. J Clin Periodontol. 1998;25:953–958. doi: 10.1111/j.1600-051X.1998.tb02397.x. [PubMed] [Cross Ref]
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. [PubMed]
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. [PubMed]
19. Malmsten M, Lindman B. Self-assembly in aqueous block copolymer solutions. Macromolecules. 1992;25:5440–5445. doi: 10.1021/ma00046a049. [Cross Ref]
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. doi: 10.1002/jbm.820060609. [PubMed] [Cross Ref]
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. doi: 10.1007/BF02545595. [Cross Ref]
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. doi: 10.1016/0378-5173(82)90114-4. [Cross Ref]
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. doi: 10.1016/S0928-0987(97)10004-5. [PubMed] [Cross Ref]
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. doi: 10.1016/0378-5173(83)90064-9. [Cross Ref]
25. Food Chemical Codex. 5th ed. Washington, DC: National Academies Press; 2003. pp. 495–496.
26. Turesky S, Gilmore ND, Glickman I. Reduced plaque formation by the chloromethyl analogue of vitamin C. J Periodontol. 1970;41:41–43. [PubMed]
27. Loee H, Silness J. Periodontal disease in pregnancy. Acta Odontol Scand. 1963;21:533–542. doi: 10.3109/00016356309011240. [PubMed] [Cross Ref]
28. Muhlemann HR, Son S. Gingival sulcus bleeding—a leading symptom in initial gingivitis. Helv Odontol Acta. 1971;15:107–113. [PubMed]
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. [PubMed]
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. doi: 10.1006/jcis.2002.8417. [PubMed] [Cross Ref]
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. doi: 10.1021/ma00093a016. [Cross Ref]
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. doi: 10.1006/jcis.1997.4880. [PubMed] [Cross Ref]
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. doi: 10.1007/s002890050007. [Cross Ref]
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. doi: 10.1006/jcis.1999.6273. [PubMed] [Cross Ref]
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. doi: 10.1016/0378-5173(96)04649-2. [Cross Ref]
36. Shah JC, Sadhale Y, Chilukuri DM. Cubic phase gels as drug delivery systems. Adv Drug Deliv Rev. 2001;47:229–250. doi: 10.1016/S0169-409X(01)00108-9. [PubMed] [Cross Ref]
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. doi: 10.1021/js970034d. [PubMed] [Cross Ref]
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. doi: 10.1111/j.1600-051X.1991.tb01699.x. [PubMed] [Cross Ref]

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