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. 2015 Feb 19;3(3):32–38. doi: 10.1007/BF02830618

Mucoadhesive vaginal tablets as veterinary delivery system for the controlled release of an antimicrobial drug, acriflavine

Elisabetta Gavini 1,✉, Vanna Sanna 1, Claudia Juliano 1, Maria Cristina Bonferoni 2, Paolo Giunchedi 1,✉
PMCID: PMC2784049  PMID: 12916935

Abstract

The aim of the study was the development of mucoadhesive vaginal tablets designed for the local controlled release of acriflavine, an antimicrobial drug used as a model. The tablets were prepared using drug-loaded chitosan microspheres and additional excipients (methylcellulose, sodium alginate, sodium carboxymethylcellulose, or. Carbopol 974). The microspheres were prepared by a spray-drying method, using the drug to polymer weight ratios 1∶1 and 1∶2 and were characterized in terms of morphology, encapsulation efficiency, and in vitro release behavior, as MIC (Minimum Inhibitory Concentration), MBC (Minimum Bacterial Concentration), and killing time (KT). The tablets were prepared by direct compression, characterized by in vitro drug release and in vitro mucoadhesive tests. The microparticles have sizes of 4 to 12 μm; the mean encapsulation yields are about 90%. Acriflavine, encapsulated into the polymer, maintains its antibacterial activity; killing time of the encapsulated drug is similar to that of the free drug. In vitro release profiles of tablets show differences depending on the excipient used. In particular Carbopol 974, which is highly cross-linked, is able to determine a drug-controlled release from the matrix tablets for more than 8 hours. The in vitro adhesion tests, carried out on the same formulation, show a good adhesive behavior. The formulation containing microspheres with drug to polymer weight ratios of 1∶1 and Carbopol 974 is characterized by the best release behavior and shows good mucoadhesive properties. These preliminary data indicate that this formulation can be proposed as a mucoadhesive vaginal delivery system for the controlled release of acriflavine.

Keywords: Chitosan, acriflavine, veterinary dosage form, vaginal delivery systems, microspheres, mucoadhesive tablets

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References

  • 1.Rothen-Weinhold R, Gurny MD. Formulation and technology aspects of controlled drug delivery in animals. Pharm Sci Technol Today. 2000;3:222–231. doi: 10.1016/S1461-5347(00)00276-5. [DOI] [PubMed] [Google Scholar]
  • 2.Vermani K, Garg S. The scope and potential of vaginal drug delivery. Pharm Sci Technol Today. 2000;3:359–364. doi: 10.1016/S1461-5347(00)00296-0. [DOI] [PubMed] [Google Scholar]
  • 3.Robinson JR, Bologna WJ. Vaginal and reproductive system treatments using a bioadhesive polymer. J Control Release. 1994;28:87–94. doi: 10.1016/0168-3659(94)90156-2. [DOI] [Google Scholar]
  • 4.Brown J, Hooper G, Kenyon CJ, Haines S, Burt J, Humphries JM, Newman SP, Davis SS, Sparrow RA, Wilding IR. Spreading and retention of vaginal formulations in post-menopausal women as assessed by gamma scintigraphy. Pharm Res. 1997;28:1073–1078. doi: 10.1023/A:1012113714552. [DOI] [PubMed] [Google Scholar]
  • 5.Lee JW, Park JH, Robinson JR. Bioadhesive-based dosage forms: the next generation. J Pharm Sci. 2000;89:850–866. doi: 10.1002/1520-6017(200007)89:7<850::AID-JPS2>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  • 6.Giunchedi P, Juliano C, Gavini E, Cossu M, Sorrenti M. Formulation and in vivo evaluation of chlorhexidine buccal tablets prepared using drug loaded chitosan microspheres. Eur J Pharm & Biopharm. 2002;52(2):233–239. doi: 10.1016/S0939-6411(01)00237-5. [DOI] [PubMed] [Google Scholar]
  • 7.Peh KK, Wong CF. Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties. J Pharm Sci. 1999;2:53–61. [PubMed] [Google Scholar]
  • 8.Parodi B, Russo E, Gatti P, Cafaggi S, Bignardi G. Development and in vitro evaluation of buccoadhesive tablets using a new model substrate for bioadhesion measures: the eggshell membrane. Drug Dev & Ind Pharm. 1999;25:289–295. doi: 10.1081/DDC-100102173. [DOI] [PubMed] [Google Scholar]
  • 9.Ugwoke MI, Exaud S, Van Den Mooter G, Verbeke N, Kinget R. Bioavailability of apomorphine following intranasal administration of mucoadhesive drug delivery systems in rabbits. Eur J Pharm Sci. 1999;9:213–219. doi: 10.1016/S0928-0987(99)00061-5. [DOI] [PubMed] [Google Scholar]
  • 10.Lim ST, Martin GP, Berry DJ, Brown MB. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release. 2000;66:281–292. doi: 10.1016/S0168-3659(99)00285-0. [DOI] [PubMed] [Google Scholar]
  • 11.Valenta C, Kast CE, Harich I, Bernkop-Schnurch A. Development and in vitro evaluation of a mucoadhesive vaginal delivery system for progesterone. J Control Release. 2001;77:323–332. doi: 10.1016/S0168-3659(01)00520-X. [DOI] [PubMed] [Google Scholar]
  • 12.Genc L, Oguzlar C, Guler E. Studies on vaginal bioadhesive tablets of acyclovir. Pharmazie. 2000;22:297–299. [PubMed] [Google Scholar]
  • 13.Ceschel GC, Maffei P, Borgia SL, Rossi S. Development of a mucoadhesive dosage form for vaginal administration. Drug Dev & Ind Pharm. 2001;27:541–547. doi: 10.1081/DDC-100105179. [DOI] [PubMed] [Google Scholar]
  • 14.Lee CH, Chien YW. Development and evaluation of a mucoadhesive drug delivery system for dual-controlled delivery of Nonoxynol-9. J Control Release. 2002;39:93–103. doi: 10.1016/0168-3659(95)00142-5. [DOI] [Google Scholar]
  • 15.Brannon-Peppas L. Novel vaginal drug release applications. Adv Drug Deliv Rev. 1993;11:169–177. doi: 10.1016/0169-409X(93)90031-X. [DOI] [Google Scholar]
  • 16.Budavari Susan., editor. The Merck Index. 11th ed. Rahway, NJ: Merck & Co. Inc; 1989. pp. 118–118. [Google Scholar]
  • 17.Martins NE, Silva MCS, Costa GM, Haddad JPA, Leite RC. Use of acriflavine for treatment of bovine trichomoniasis. Revista Brasileira de Reproducao Animal. 1997;21(2):168–169. [Google Scholar]
  • 18.Muzzarelli RAA, Baldassare V, Conti F, Gazzanelli G, Vasi V, Ferrara P, Biagini G. The biological activity of chitosan: ultrastructural study. Biomaterials. 1988;8:247–252. doi: 10.1016/0142-9612(88)90092-0. [DOI] [PubMed] [Google Scholar]
  • 19.Singla AK, Chawla M. Chitosan: some pharmaceutical and biological aspects—an update. J Pharm Pharmacol. 2001;53:1047–1067. doi: 10.1211/0022357011776441. [DOI] [PubMed] [Google Scholar]
  • 20.Kan TA, Peh KK, Ching HS. Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing. J Pharma Pharmaceut Sci. 2000;3:303–311. [PubMed] [Google Scholar]
  • 21.Conti B, Giunchedi P, Genta I, Conte U. The preparation and in vitro evaluation of the wound-healing properties of chitosan microspheres. STP Pharma Sci. 2000;10:101–104. [Google Scholar]
  • 22.Edmundson IC. In: Advances in Pharmaceutical Sciences. Bean HS, Carless JE, Beckett AH, editors. New York, NY: Academic Press; 1967. pp. 95–95. [Google Scholar]
  • 23.Thrupp LD. Susceptibility testing of antibiotics in liquid media. In: Lorian V, editor. Antibiotics in Laboratory Medicine. Baltimore, MD: William & Wilkins; 1986. pp. 93–150. [Google Scholar]
  • 24.Ferrari F, Bertoni M, Rossi S, Bonferoni MC, Caramella C, Waring MJ, Aulton ME. Comparative rheo-mechanical and adhesive properties of two hydrocolloid dressings: dependence on the degree of hydration. Drug Dev & Ind Pharm. 2002;22:1223–1230. doi: 10.3109/03639049609063241. [DOI] [Google Scholar]
  • 25.Macleod GS, Collett JH, Fell JT. The potential use of mixed films of pectin, chitosan and HPMC for bimodal drug release. J Control Release. 1999;58:303–310. doi: 10.1016/S0168-3659(98)00168-0. [DOI] [PubMed] [Google Scholar]

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