Fabrication and in vitro evaluation of subgingival strips of calcium alginate for controlled delivery of ofloxacin and metronidazole
Keywords:
Biodegradable, Polymer Biphasic drug release, Calcium Alginate, Controlled Release, Subgingival stripsAbstract
Aim: Subgingival strips of combined ofloxacin (OFX) and metronidazole (MET) were fabricated and evaluated in vitro using biodegradable calcium alginate.
Methods: Strips of drug:polymer (10:90, 25:75, 50:50 and 75:25) were prepared using solvent casting method. A 10%w/v CaCl2 solution was used for gelation of the strips.
Results: The thickness of strips were at par of recommended thickness (<320 μm). In vitro release of drugs followed a biphasic kinetics which was sufficient to maintain the minimum inhibitory concentrations (MIC) to inhibit the growth of the microorganisms for 5 days. The rate of drug release was inversely proportional to polymer concentration in the formulations. The drug release was by diffusion in second phase of dissolution.
Conclusions: The formulations OM1 and OM2 which contain 90 and 75%w/w of polymer could be employed for controlled delivery of combined OFX and MET for 5 days in subgingival infections. Calcium alginate, being a biodegradable is a good choice as drug retarding polymer.
Downloads
References
Goodson JM. Antimicrobial strategies for treatment of periodontal diseases. Periodontol. 1994; 5: 142-168.
Academy Report. American academy of periodontology, position paper. Systemic antibiotics in periodontics. J Periodont. 2004; 75: 1553–65.
Goodson JM, Offenbacher S, Farr DH, Hogan PE. Periodontal disease treatment by local drug delivery. J Periodont. 1985; 56: 265-72.
Elkayam R, Friedman M, Stabholz A, Soskolne AW, Azoury R. Sustained release device of tetracycline for dental use, structure and kinetics of drug release in vitro and in vivo. Proc Int Conf Pharm Tech. 1989; 2: 346–54.
Stabholz A, Soskolne WA, Friedman M, Sela MN. The use of sustained release delivery of chlorhexidine for the maintenance of periodontal pockets: 2 year clinical trial. J Periodont. 1991; 62: 429–33.
Stoltze K. Concentration of metronidazole in periodontal pockets after application of a metronidazole 25% dental gel. J Clin Perio. 1992; 19: 698–701.
Okuda K, Wolff L, Oliver R, Osborn J, Stoltenberg J, Bereuter J. Minocycline slow release formulation effect on subgingival bacteria. J Periodont. 1992; 63 (2):73–9.
Medlicott NJ, Jones DS, Tucker IG, Holborow D. Preliminary release studies of chlorhexidine (base and diacetate) from poly (gecaprolactone) films prepared by solvent evaporation. Int J Pharm. 1992; 84: 85–89.
Norling T, Lading P, Engstrom S, Larsson K, Krog N, 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 Perio. 1992; 19: 687–92.
Minabe M, Uematsu A, Nishijima K, Tomomatsu E, Tamura T, Hori T. Application of a local drug delivery system to periodontal therapy: 1. Developement of collagen preparations with immobilized tetracycline. J Periodont. 1989; 60: 113–7.
Chung TW, Yang J, Akaike T, Cho KY, Nah JW, Kim SI et al. Preparation of alginate/galactosylated chitosan scaffold for hepatocyte attachment. Biomaterials. 2002; 23: 2827–34.
Raymond CR, Paul JS, Marian EQ. Handbook of Pharmaceutical Excipients. 6ª ed. London: Pharmaceutical Press; 2009. 917.
Pluta J, Haznar D. Properties and active substance release kinetics from gelatin-alginate matrices. Polim Med. 2006; 36:55–69.
Boateng JS, Auffret AD, Matthews KH, Humphrey MJ, Stevens HN, Eccleston GM. Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces. Int J Pharm. 2010; 389:24–31.
Satishbabu BK, Srinivasan BP. Preparation and evaluation of buccoadhesive films of atenolol. J Pharm Sci. 2008; 70:175-9.
Trezubov VN, Kobzev SA, Lobanov SA, Akulovich AV. The use of new biologically compatible materials in the combined treatment of periodontal diseases. Stomatologiia (Mosk). 1996; 75:59–61.
Steve WNU, Mel SL, Song-Shu L, Err-Cheng C, Shih-Jung L. Development of a biodegradable alginate carrier system for antibiotics and bone cells. J Ortho Res. 2006; 25:62–72.
Bahlul ZA, Prakash K, Chandu BR, Soad AM, Turkiya OA. Design and in-vitro evaluation of controlled release cephalexin subgingival films using natural biodegradable polymer. Rec Res Sci Tech. 2010; 2:6–11.
The United States Pharmacopoeia 30-National Formulary 25. Rockville, MD: United States Pharmacopoeial Convention; 2007. p 2653.
Steven G, Judith AO. Anti-infectives In: Lippincott Williams and Wilkins, editors. Remington: The Science and Practice of Pharmacy. 21ª ed. Philadelphia: Lippincott Williams and Wilkins. 2005: p. 1658-9.
Antonio DD, Piccotomini R, Lacone A, Fioritoni G, Pamiti G, Betti S et al. Comparison of ciprofloxacin, ofloxacin and pefloxacin for the prevention of the bacterial infection in neutropenic patients with haematological malignancies. J Antimicrob Chemother. 1994; 33:837–41.
Kimura S, Toda H, Shimabukuro Y, Kitamura M, Fujimoto N, Miki Y. Topical chemotherapy in human periodontitis using a new controlled-release insert containing ofloxacin. I. Microbiological observation. J Periodontal Res. 1991; 26(1):33–41.
Higashi K, Morisaki K, Hayashi S, Kitamura M, Fujimoto N, Kimura A, et al. Local ofloxacin delivery using a controlled-release insert (PT-01) in the human periodontal pocket. J Periodontal Res. 1990; 25:1–5.
The United States Pharmacopoeia 30-National Formulary 25. Rockville, MD: United States Pharmacopoeial Convention; 2007. p 2653.
Margaret A, Phillips SL, Stanley JR. Chemotherapy of Protozoal Infections: Amebiasis, Giardiasis, Trichomoniasis, Trypanosomiasis, Leishmaniasis, and Other Protozoal Infections. In: Laurence LB, editor. Goodman & Gilman's: the pharmacologic basis of therapeutics. New York: McGraw-Hill Professional. 11th ed. 2006. P. 1658.
Wright TL, Ellen RP, Lacroix JM, Sinnadurai S, Mittelman MW. Effects of metronidazole on Porphyromonas gingivalis biofilms. J Periodon Res. 1997; 32:473–7.
Shifrovitch Y, Binderman I, Bahar H, Berdicevsky I, Zilberman M. Metronidazole-loaded bioabsorbable films as local antibacterial treatment of infected periodontal pockets. J Periodontol. 2009; 80:330–7.
El-Kamel AH, Ashri LY, Alsarra IA. Micromatricial metronidazole benzoate strip as a local mucoadhesive delivery system for treatment of periodontal diseases. AAPS PharmSciTech. 2007; 8:E75.
Bickel M, Munoz JL, Giovannini P. Acid-base properties of human gingival crevicular fluid. J Dent Res. 1995; 64: 1218–20.
Divya PV, Nandakumar K. Local Drug Delivery-Periocol in Periodontics. Trends Biomater Artif Organs. 2006; 19:74-80.
Ellie JCG, Diane MC. Comparative activity of ciprofloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, CI-990, and WIN 57273 against anaerobic bacteria. Antimicrob Agents Chemother. 1992; 36: 1158-62.
Downloads
Published
How to Cite
Issue
Section
License
The articles, which are published in this journal, are subject to the following terms in relation to the rights of patrimonial or exploitation:
- The authors will keep their copyright and guarantee to the journal the right of first publication of their work, which will be distributed with a Creative Commons BY-NC-SA 4.0 license that allows third parties to reuse the work whenever its author, quote the original source and do not make commercial use of it.
b. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (e.g., deposit it in an institutional telematic file or publish it in a monographic volume) provided that the original source of its publication is indicated.
c. Authors are allowed and advised to disseminate their work through the Internet (e.g. in institutional repositories or on their website) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).
