• Sanjeevani S. Deshkar RTM Nagpur University
  • Arun T. Patil RTM Nagpur University
  • Sushilkumar S. Poddar Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri


Objective: The aim of the present study was to develop in-situ gelling formulations of Fluconazole (FCZ) using thermosensitive polymer for treatment of vaginal Candidiasis.

Methods: In-situ gelling formulations of FCZ (1 % w/w) were prepared with different concentrations of Poloxamer 407 (P 407, 15-20% w/w) using the cold dispersion method. Similarly,  formulations were also prepared by adding mucoadhesive polymers like hydroxyethyl cellulose, Polycarbophil, Carbopol 974 and Hydroxypropyl methylcellulose E 50 LV (0.4 % w/w) to the P 407 formulations. These formulations were evaluated for appearance, clarity, pH, gelling ability, gelling time, gelling temperature, viscosity (in sol and gel forms), spreading time, ex-vivo mucoadhesion, in-vitro dissolution, morphological characteristics by SEM and in-vitro antifungal efficacy against Candida albicance. In-vivo vaginal irritation of developed formulation was assessed in New Zealand female rabbits.

Results: In-situ gelling formulation of FCZ, prepared using 18 % w/w P407 and 0.4 % hydroxyethyl cellulose, was optimized since this formulation was found to be clear, transparent, forming a quick and stable gel with shear thinning behaviour and excellent mucoadhesion. The developed formulation released 74.21% of FCZ after 8 h of dissolution in 5.2 pH citrate buffer. In-vitro antifungal activity against Candida albicance showed the stronger antifungal activity of formulation as compared to a marketed formulation. In-vivo vaginal irritation study in rabbits demonstrated no significant irritation after 10 d of exposure to the formulation.

Conclusion: The study demonstrated that in-situ gelling formulation of FCZ prepared using thermosensitive polymer had improved activity against Candida albicance and would be efficacious for the treatment of vaginal Candidiasis.

Keywords: Fluconazole, Vaginal drug delivery, In-situ gel, Poloxamer, Candidiasis


Download data is not yet available.


1. Acarturk F. Mucoadhesive vaginal drug delivery systems. Recent Pat Drug Delivery Formulation 2009;3:193-205.
2. Meng J, Sturgis TF, Youan B-BC. Engineering tenofovir loaded chitosan nanoparticles to maximize microbicide mucoadhesion. Eur J Pharm Sci 2011;44:57-67.
3. Patel N, Thakkar V, Moradiya P, Gandhi T, Gohel M. Optimization of curcumin loaded in-situ vaginal hydrogel by Box-Behnken statistical design for contraception. J Drug Delivery Sci Technol 2015;29:55-69.
4. Iyer V, Poddar SS. Update on Nonoxynol-9 as a vaginal spermicide. Eur J Contracept Reprod Health Care 2008;13:339-50.
5. Debata PR, Castellanos MR, Fata JE, Baggett S, Rajupet S, Szerszen A, et al. A novel curcumin-based vaginal cream vacurin selectively eliminates apposed human cervical cancer cells. Gynecol Oncol 2013;129:145-53.
6. Bachhav YG, Patravale VB. The microemulsion based vaginal gel of fluconazole: formulation, in vitro and in vivo evaluation. Int J Pharm 2009;365:175-9.
7. Tugcu-Demiroz F, Acarturk F, Erdogan D. Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations. Int J Pharm 2013;457:25-39.
8. Kammona O, Kiparissides C. Recent advances in nanocarrier based mucosal delivery of biomolecules. J Controlled Release 2012;161:781-94.
9. Vermani K, Garg S. The scope and potential of vaginal drug delivery. Pharm Sci Technol Today 2000;3:359-64.
10. Valenta C. The use of mucoadhesive polymers in vaginal delivery. Adv Drug Delivery Rev 2005;57:1692-712.
11. Kast CE, Valenta C, Leopold M, Bernkop-Schnürch A. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for Clotrimazole. J Controlled Release 2002;81:347-54.
12. das Neves J, Bahia MF. Gels as vaginal drug delivery systems. Int J Pharm 2006;318:1-14.
13. Baloglu E, Karavana SY, Senyigit ZA, Hilmioglu-Polat S, Metin DY, Zekioglu O, et al. In-situ gel formulations of Econazole nitrate: preparation and in-vitro and in-vivo evaluation. J Pharm Pharmacol 2011;63:1274-82.
14. Baloglu E, Senyigit ZA, Karavana SY, Bernkop-Schnurch A. Strategies to prolong the intra-vaginal residence time of drug delivery systems. J Pharm Pharm Sci 2009;12:312-36.
15. Ibrahim el SA, Ismail S, Fetih G, Shaaban O, Hassanein K, Abdellah NH. Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application. Acta Pharm 2012;62:59-70.
16. Patel P. Formulation and evaluation of clindamycin HCL in situ gel for vaginal application. Int J Pharm Invest 2015;5:50-6.
17. Liu Y, Zhu YY, Wei G, Lu WY. Effect of carrageenan on poloxamer-based in situ gel for vaginal use: improved in vitro and in vivo sustained-release properties. Eur J Pharm Sci 2009;37:306-12.
18. Mayol L, Quaglia F, Borzacchiello A, Ambrosio L, Rotonda MIL. A novel poloxamers/hyaluronic acid in situ forming hydrogel for drug delivery: Rheological, mucoadhesive and in vitro release properties. Eur J Pharm Biopharm 2008;70:199-206.
19. Zhao XY, Xu J, Zheng LQ, Li X-W. Preparation of temperature-sensitive microemulsion-based gels formed from a triblock copolymer. Colloids Surf A 2007;307:100-7.
20. He C, Kim SW, Lee DS. In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. J Controlled Release 2008;127:189-207.
21. Singh NK, Lee DS. In situ gelling pH-and temperature-sensitive biodegradable block copolymer hydrogels for drug delivery. J Controlled Release 2014;193:214-27.
22. Tasoglu S, Katz DF, Szeri AJ. Transient spreading and swelling behaviour of a gel deploying an anti-HIV topical microbicide. J Non-Newtonian Fluid Mech 2012;187-188:36-42.
23. Furst T, Piette M, Lechanteur A, Evrard B, Piel G. Mucoadhesive cellulosic derivative sponges as drug delivery system for vaginal application. Eur J Pharm Biopharm 2015;95:128-35.
24. Hiorth M, Liereng L, Reinertsen R, Tho I. Formulation of bioadhesive hexyl aminolevulinate pellets intended for photodynamic therapy in the treatment of cervical cancer. Int J Pharm 2013;441:544-54.
25. Ekiert RJ, Krzek J, Talik P. Chromatographic and electrophoretic techniques used in the analysis of triazole antifungal agents-a review. Talanta 2010;82:1090-100.
26. Zhang L, Parsons DL, Navarre C, Kompella UB. Development and in-vitro evaluation of sustained release poloxamer 407 (P407) gel formulations of Ceftiofur. J Controlled Release 2002;85:73-81.
27. Manjappa AS, Nanjwade BK, Manvi FV, Murthy RSR. Sustained ophthalmic in situ gel of Ketorolac tromethamine: rheology and in vivo studies. Drug Dev Res 2009;70:417-24.
28. Zaki NM, Awad GA, Mortada ND, Abd ElHady SS. Enhanced bioavailability of Metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci 2007;32:296-307.
29. Shinde JV, Dias RJ, Havaldar VD, Mahajan NS. In situ mucoadhesive nasal gels of metoclopramide hydrochloride: formulation and formulation studies. J Pharm Res 2008;1:88-96.
30. Andrews GP, Donnelly L, Jones DS, Curran RM, Morrow RJ, Woolfson AD, et al. Characterization of the rheological, mucoadhesive, and drug release properties of highly structured gel platforms for intravaginal drug delivery. Bio-macromolecules 2009;10:2427-35.
31. Aka-Any-Grah A, Bouchemal K, Koffi A, Agnely F, Zhang M, Djabourov M, et al. Formulation of mucoadhesive vaginal hydrogels insensitive to dilution with vaginal fluids. Eur J Pharm Biopharm 2010;76:296-303.
32. Kim YT, Shin BK, Garripelli VK, Kim JK, Davaa E, Jo S, et al. A thermosensitive vaginal gel formulation with HPgammaCD for the pH-dependent release and solubilization of Amphotericin B. Eur J Pharm Sci 2010;41:399-406.
33. Abdel-Hamid SM, Abdel-Hady SE, El-Shamy AA, El-Dessouky HF. Formulation of an antispasmodic drug as a topical local anaesthetic. Int J Pharm 2006;326:107-18.
34. Abruzzo A, Bigucci F, Cerchiara T, Saladini B, Gallucci MC, Cruciani F, et al. Chitosan/alginate complexes for vaginal delivery of chlorhexidine digluconate. Carbohydr Polym 2013;91:651-8.
35. Han IK, Kim YB, Kang HS, Sul D, Jung WW, Cho HJ, et al. Thermosensitive and mucoadhesive delivery systems of mucosal vaccines. Methods 2006;38:106-11.
36. Lin HR, Sung KC. Carbopol/pluronic phase change solutions for ophthalmic drug delivery. J Controlled Release 2000; 69:379-88.
37. Ivanova R, Alexandridis P, Lindman BR. Interaction of poloxamer block copolymers with cosolvents and surfactants. Colloids Surf A 2001;183-185:41-53.
38. 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.
39. Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RF. A poloxamer/Chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm 2010;75:186-93.
40. Qi H, Chen W, Huang C, Li L, Chen C, Li W, et al. Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin. Int J Pharm 2007;337:178-87.
41. Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RS. Thermoreversible-mucoadhesive gel for nasal delivery of sumatriptan. AAPS PharmSciTech 2006;7:67.
42. Srividya B, Cardoza RM, Amin PD. Sustained ophthalmic delivery of Ofloxacin from a pH triggered in situ gelling system. J Controlled Release 2001;73:205-11.
796 Views | 1620 Downloads
How to Cite
Deshkar, S. S., A. T. Patil, and S. S. Poddar. “DEVELOPMENT OF THERMOSENSITIVE GEL OF FLUCONAZOLE FOR VAGINAL CANDIDIASIS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 1, Dec. 2015, pp. 391-8,
Original Article(s)