A New In-Situ Gel Formulation of Itraconazole for Vaginal Administration

DOI: 10.4236/pp.2012.34056   PDF   HTML     4,563 Downloads   10,079 Views   Citations


In this paper, mucoadhesive in-situ gel with poloxamer and hydroxypropylmethylcellulose formulations of itraconazole were prepared for vaginal application. In addition, rheological, mechanical and mucoadhesive properties and syringeability of the formulations were characterized. The mixtures of Poloxamer 407 and 188 with two different types of hydroxypropylmethylcellulose were used as polymers for gel formulations. Flow rheometry studies and oscillatory analysis of each formulation were performed at 20℃ ± 0.1℃ and 37℃ ± 0.1℃. All formulations exhibited pseudo-plastic flow and typical gel-type mechanical spectra (G′ > G″) after the determined frequency value at 37℃. Texture profile analysis presented that F3 formulation containing 20% poloxamer 407, 10% poloxamer 188 and 0.5% hydroxypropylmethylcellulose appeared to offer more suitable mechanical and mucoadhesive performance. Using different hydroxypropylmethylcellulose type in formulations didn’t significantly change syringeability values. The evaluation of the entire candidate formulations indicated that vaginal formulation of itraconazole will be an alternative for the treatment of vaginal candidiasis with suitable textural and rheological properties. Our results showed that the developed formulations were found worthy of further studies.

Share and Cite:

S. Karavana, S. Rençbe, Z. Şenyiğit and E. Baloğlu, "A New In-Situ Gel Formulation of Itraconazole for Vaginal Administration," Pharmacology & Pharmacy, Vol. 3 No. 4, 2012, pp. 417-426. doi: 10.4236/pp.2012.34056.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Six, K, Daems, T, Hoon, J, Hecken, AV, Depre, M, Bouche, MP, Prinsen, P, Verreck, G, Peeters, J, Brewster, ME, Mooter, GV. Clinical study of solid dispersions of itraconazole prepared by hot-stage extrusion. Eur J Pharm Sci. 2005; 24:179-186.
[2] Grant, S, Clissold, S. Itraconazole: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in superficial and systemicmycoses. Drugs. 1989; 37:310–344.
[3] Yi, Y, Yoon, HJ, Kim, BO, Shim, M, Kim, SO, Hwang, SJ, Seo MH. A mixed polymeric miceller formulation of itraconazole: characteristics, toxicity and pharmacokinetics. J Control Release. 2007; 117:59-67.
[4] Odds, FC. Itraconazole-a new oral antifungal agent with a very broad spectrum of activity in superficial and systemic mycoses. J Dermatol Sci. 1993; 5:65-72.
[5] Gupta, AK, Bluhm, R. Itraconazole (Sporanox) for Vulvovaginal Candidiasis. Skin Therapy Lett. 2002; 7:1-3.
[6] Stein, G. E., Mummaw, N. Placebo-Controlled Trial of Itraconazole for Treatment of Acute Vaginal Candidiasis. Antimicrob Agents Chemother. 1993; 37:89-92.
[7] Baloglu, E, Karavana, SY, Ay Senyigit, Z, Guneri, T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm Dev Tech. 2011; 16:627-636.
[8] Gurny, R, Meyer, JM., Peppas, NA. Bioadhesive intraoral release systems: design, testing and analysis. Biomaterials. 1984; 5:336-340.
[9] Masteikova, R, Chalupova, Z, Sklubalova, Z. Stimuli sensitive hydrogels in controlled and sustained drug delivery. Medicina. 2003; 39:19–24.
[10] Morishita, M, Barichello JM, Takayama, K, Chiba, Y, Tokiwa, S, Nagai, T. Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insülin. Int J Pharm. 2001; 212:289–293.
[11] Jones, DS, Brown, AF, Woolfson, AD. Solute and solvent effects on the thermorheological properties of poly(oxyethylene)–poly(oxypropylene) block copolymers: implications for pharmaceutical dosage form design. J Appl Polym Sci. 2003; 87:1016–1026.
[12] Alexandiridis, P, Hatton, TA. Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer surfactants in aqueous solutions and interfaces: thermodynamics, structure, dynamics and modeling. Colloids Surf A. 1995; 96:1–46.
[13] Kabanov, AV, Batrakova, EV, Alakhov, VY. Pluronic? block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release. 2002; 82:521–533.
[14] Wang, L, Tang, X. A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: Design, in vitro and in vivo evaluation. Int J Pharm. 2008; 350:181-187.
[15] Sudeendra, BR, Umme, H, Gupta, RK, Shivakumar, HG. Development and characterization of bioadhesive vaginal films of clotrimazole for vaginal candidiasis. Acta Pharm Sci. 2010; 52:417-426.
[16] http://www.dow.com/dowexcipients/products/methocel.htm.
[17] Choi H, Jung JH, Ryu, JM, Yoon, SJ, Oh, YK, Kim, CK. Development of in-situ gelling and mucoadhesive acetaminophen liquid suppository. Int J Pharm. 1998; 165:33-44.
[18] Chang, JY, Oh, YK, Choi, H, Kim, YB, Kim, CK. Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int J Pharm. 2002; 241:155-163.
[19] Jones, DS, Woolfson, AD, Djokic, J, Coulter, WA. Development and mechanical characterisation of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharm Res. 1996; 13:1734-1738.
[20] Baloglu, E, Karavana, SY, Ay Senyigit, Z, Hilmioglu-Polat, S, Metin, D Y, Zekioglu O, Guneri, T, Jones, DS. In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation. J Pharm Pharmacol. 2011; 63:1274-1282.
[21] Jones, DS, Woolfson, AD, Brown, AF. Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. J Control Release. 2000; 67:357–368.
[22] Burckbuchler, V, Mekhloufi, G, Paillard Giteau, A, Grossiord, JL, Huille, S, Agnely, F. Rheological and syringeability properties of highly concentrated human polyclonal immunoglobulin solutions. Eur J Pharm Biopharm. 2010; 76:351–356.
[23] Jones, DS, Woolfson, AD, Brown, AF. Textural, analysis and flow rheometry of novel, bioadhesive antimicrobial oral gels. Pharm Res. 1997; 14:450-457.
[24] Jones, DS, Woolfson, AD, Brown, AF. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers. Int J Pharm. 1997; 151:223–233.
[25] Andrews, GP, Gorman, SP, Jones, DS. Rheological characterisation of primary and binary interactive bioadhesive gels composed of cellulose derivatives designed as ophthalmic viscosurgical devices. Biomaterials. 2005; 26:571–580.
[26] Andrews, GP, Jones, DS. Rheological characterization of bioadhesive binary polymeric systems designed as platforms for drug delivery implants. Biomacromolecules. 2006; 7:899–906.
[27] Neves, J, Amaral Maria, H, Bahia Maria, F. Performance of an in vitro mucoadhesion testing method for vaginal semisolids: influence of different testing conditions and instrumental parameters. Eur J Pharm Biopharm. 2008; 69:622–632.
[28] Kramaric A, Resman A, Kofler, B, Zmitek, J. Thermoreversible gel as a liquid pharmaceutical carrier for a galenic formulation. European Patent. 1992.
[29] Miyazaki S, Suisha, F, Kawasaki, N, Shirakawa, M, Yamatoya, K, Attwood, D. Thermally reversible xyloglucan gels as vehicles for rectal drug delivery. J Control Rel. 1998; 56:75–83.
[30] Edsman K, Carlfors J, Petersson R. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. Eur J Pharm Sci. 1998; 6:105–112.
[31] Xuan J, Balakrishnan P, Oh DH, Yeo WH, Park SM, Yong CS, Choi HG. Rheological characterization and in vivo evaluation of thermosensitive poloxamer-based hydrogel for intramuscular injection of piroxicam. Int J Pharm. 2010; 395:317–323.
[32] Chang JY, Oh YK, Kong HS, Kim EJ, Jang DD, Nam KT, Kim CK. Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis. J Control Release. 2002; 82:39–50.
[33] Jones DS, Woolfson AD, Dkokic J. Texture profile analysis of bioadhesive polymeric semisolids: Mechanical characterization and investigation of interactions between formulation components. J Appl Polym Sci. 1996; 61:2229–2234.
[34] Bruschi, ML, Jones, DS, Panzeri, H, Gremiao, MP, Freitas, O, Lara, EH. Semisolid systems containing propolis for the treatment of periodontal disease: in vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties. J Pharm Sci. 2007; 96:2074-2089.
[35] Jones, DS., Lawlor, MS, Woolfson, AD. Rheological and mucoadhesive characterization of polymeric systems composed of poly(methylvinyletherco-maleic anhydride) and poly(vinylpyrrolidone), designed as platforms for topical drug delivery. J Pharm Sci. 2003; 92:995-1007.
[36] Cevher, E, Sensoy, D, Taha, MAM, Araman, A. Effect of Thiolated Polymers to Textural and Mucoadhesive Properties of Vaginal Gel Formulations Prepared with Polycarbophil and Chitosan. AAPS PharmSciTech. 2008; 9(3):953-965.
[37] Yong, CS, Choi, JS, Quan, QZ, Rhee, JD, Kim, CK, Lim, SJ, Oh, PS, Choi, HG. Effect of sodium chloride on the gelation tem perature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium. Int J Pharm. 2001; 226:195–205.
[38] Ross-Murphy, SB. Physical gelation of synthetic and biological macromolecules. In: DeRossi D et al, ed. Polyer Gels: Fundamentals and Biomedical Application. NewYork: Plenum Press. 21–39, 1991.
[39] Ikeda, S, Nishinari, K. Weak gel-type rheological properties of aqueous dispersions of nonaggregated K-carragenan helices. J Agric Food Chem. 2001; 49:4436–4441.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.