Research Article
Microemulsion Based Bioadhesive Gel of Itraconazole Using Tamarind Gum: In-vitro and Ex-vivo Evaluation
Abstract
The current study was aimed to formulate and evaluate
bioadhesive gel containing microemulsion (ME) of itraconazole
(ITZ) and an attempt was made to investigate suitability of
tamarind gum (TG) as a gelling agent. The solubility of ITZ
in oils, surfactants and co-surfactant was evaluated for the
selection of appropriate component. The ratio of surfactant and
co-surfactant was optimized by constructing pseudoternary
phase diagram. Ternary phase diagram was constructed using
isopropyl myristate (IPM) and oleic acid (OA) as oil phase, tween
80 as surfactant and isopropyl alcohol (IPA) as cosurfactant
in order to obtain ME region. The optimized ME of ITZ was
characterized by its qualitative and quantitative tests and
incorporated into polymeric gels of carbopol (CBP), xanthan
gum (XG) and TG. The ME based ITZ gels were evaluated for
pH, drug content, viscosity, ex-vivo bioadhesion, spreadability
and in vitro drug release. Furthermore, antifungal activity of
the gels was performed by agar cup diffusion technique using
cultures of Candida albicans. ITZ showed maximum solubility
in mixture of IPM and OA (1:1). Stable ME was obtained when
IPM and OA was taken in the ratio of 1:1 as oil phase, Tween 80
as surfactant and isopropyl alcohol (IPA) as cosurfactant at the
weight ratio of 10:45:45. The optimized ME based gels showed
pH in the range of 6.11 to 6.48, spreadability in the range of 4.1
to 7.1gm.cm/sec and ex vivo bioadhesion in the range of 65 to
84gm. The viscosity study indicated pseudoplastic behaviour of
all ME based gel formulations. Amongst the studied ME gels,
TG containing gels exhibited fast and complete drug release at
the end of 24h. Formulation F7 containing TG showed wide
zone of inhibition and found to be stable for three months.
These results indicate that the TG containing ME gel may be a
used as vehicle for topical delivery of drugs.
References
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Drugs 1989;37:310–44. 6. Ambala R, Vemula SK. Formulation and characterization of ketoprofen emulgels. J Appl Pharm Sci 2015;5:112–7. 7. Mohamed MI. Optimization of chlorphenesin emulgel formulation. AAPS J 2004;6:e26. 8. Khunt DM, Mishra AD, Shah DR. Formulation design & development of piroxicam emulgel. Int J PharmTech Res 2012;4:1332–44. 9. Karasulu HY. Microemulsions as novel drug carriers : the formation , stability , applications and toxicity. Expert Opin Drug Deliv 2008;5:119–36. 10. Shah VV, Sharma M, Gandhi K, Suthar V, Parikh RK. Quality by Design (QbD) approach for optimization of microemulsion based topical gel. Marmara Pharm J 2016;20:415–24. 11. Mali KK, Dhawale SC. Design and optimization of modified tamarind gum-based floating-bioadhesive tablets of verapamil hydrochloride. Asian J Pharm 2016;10:2–8. 12. Boonme P, Kaewbanjong J, Sangduangyang S, Suksawat S, Teeranachaideekul V. Microemulsion-based hydrogels of itraconazole: Evaluation of characteristics and stability. Asian J Pharm Sci 2016;11:98–9. 13. Shahin M, Hady SA, Hammad M, Mortada N. Novel jojoba oil-based emulsion gel formulations for clotrimazole delivery. AAPS PharmSciTech 2011;12:239–47. 14. Fouad SA, Basalious EB, El-Nabarawi MA, Tayel SA. Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: In vitro/in vivo evaluation. Int J Pharm 2013;453:569–78. 15. Goyal P, Kumar V, Sharma P. Carboxymethylation of Tamarind kernel powder. Carbohydr Polym 2007;69:251–5. 16. Shaw GS, Uvanesh K, Gautham SN, Singh V, Pramanik K, Banerjee I, Kumar N, Pal K. Development and characterization of gelatin-tamarind gum/carboxymethyl tamarind gum based phase-separated hydrogels:a comparative study. Des Monomers Polym 2015;18:434–50. 17. Kaur G, Jain S, Tiwary AK. Chitosan-carboxymethyl tamarind kernel powder interpolymer complexation: Investigations for colon drug delivery. Sci Pharm 2010;78:57–78. 18. Pal S, Sen G, Mishra S, Dey RK, Jha U. Carboxymethyl tamarind: Synthesis, characterization and its application as novel drug-delivery agent. J Appl Polym Sci 2008;110:392– 400. 19. Kaur H, Ahuja M, Kumar S, Dilbaghi N. Carboxymethyl tamarind kernel polysaccharide nanoparticles for ophthalmic drug delivery. Int J Biol Macromol 2012;50:833–9. 20. Madgulkar AR, Bhalekar MR, Padalkar RR, Shaikh MY. Optimization of carboxymethyl-xyloglucan-based tramadol matrix tablets using simplex centroid mixture design. J Pharm 2013;2013:1–11. 21. Datta R, Bandyopadhyay AK. A new nasal drug delivery system for diazepam using natural mucoadhesive polysaccharide obtained from tamarind seeds. Saudi Pharm J 2006;14:115–9. 22. Mali K, Dhawale S, Dias R, Havaldar V, Ghorpade V, Salunkhe N. Nasal mucoadhesive in situ gel of granisetron hydrochloride using natural polymers. J Appl Pharm Sci 2015;5:084–93. 23. Ghelardi E, Tavanti A, Davini P, Celandroni F, Salvetti S, Parisio E, Boldrini E, Senesi S, Campa M. A mucoadhesive polymer extracted from tamarind seed improves the intraocular penetration and efficacy of rufloxacin in topical treatment of experimental bacterial keratitis. Antimicrob Agents Chemother 2004;48:3396-401. 24. Avachat AM, Gujar KN, Wagh KV. Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate. Carbohydr Polym 2013;91:537–42. 25. Hou P, Cao S, Ni J, Zhang T, Cai Z, Liu J, Wang Y, Wang P, Lei H, Liu Y. In-vitro and in-vivo comparison of T-OA microemulsions and solid dispersions based on EPDC. Drug Dev Ind Pharm 2015;41:263–71. 26. Barot BS, Parejiya PB, Patel HK, Mehta DM, Shelat PK. Microemulsion-based antifungal gel delivery to nail for the treatment of onychomycosis: Formulation, optimization, and efficacy studies. Drug Deliv Transl Res 2012;2:463–76. 27. Kumar M, Pathak K, Misra A. Formulation and characterization of nanoemulsion-based drug delivery system of risperidone. Drug Dev Ind Pharm 2009;35:387–95. 28. Hong JY, Kim JK, Song YK, Park JS, Kim CK. A new selfemulsifying formulation of itraconazole with improved dissolution and oral absorption. J Control Release 2006;110:332–8. 29. Kumar R, Sinha VR. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surfaces B Biointerfaces 2014;117:82–8. 30. López-Cervantes M, Escobar-Chávez JJ, Casas-Alancaster N, Quintanar-Guerrero D, Ganem-Quintanar A. Development and characterization of a transdermal patch and an emulgel containing kanamycin intended to be used in the treatment of mycetoma caused by Actinomadura madurae. Drug Dev Ind Pharm 2009; 35:1511–21. 31. Khalil YI, Khasraghi AH, Mohammed EJ. Preparation and evaluation of physical and rheological properties of clotrimazole emulgel. Iraqui J Pharm Sci 2011;20:19–27. 32. Shen Y, Ling X, Jiang W, Du S, Lu Y, Tu J. Formulation and evaluation of Cyclosporin A emulgel for ocular delivery. Drug Deliv 2015;22:911-7. 33. Bachhav YG, Patravale VB. Formulation of meloxicam gel for topical application: In vitro and in vivo evaluation. Acta Pharm 2010;60:153–63. 34. Thakur NK, Bharti P, Mahant S, Rao R. Formulation and characterization of benzoyl peroxide gellified emulsions. Sci Pharm 2012;80:1045–60. 35. Naga Sravan Kumar Varma V, Maheshwari P V, Navya M, Reddy SC, Shivakumar HG, Gowda DV. Calcipotriol delivery into the skin as emulgel for effective permeation. Saudi Pharm J 2014;22:591-9. 36. Ismail A, Saleh KI, Ibrahim MA, Khalaf S. Effect of porous silica as a drug carrier on the release rate of naproxen from emulgel. Bull Pharm Sci 2006;29:224–35. 37. Wagh VD, Deshmukh OJ. Itraconazole niosomes drug delivery system and its antimycotic activity against Candida albicans. ISRN Pharm 2012;2012:Article ID 653435. 38. Üstündağ Okur N, Çağlar EŞ, Arpa MD, Karasulu HY. Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine. Pharm Dev Technol 2016;7450:1–11. 39. Bachhav YG, Patravale VB. Microemulsion based vaginal gel of fluconazole: Formulation, in vitro and in vivo evaluation. Int J Pharm 2009;365:175–9. 40. Yuan Y, Li SM, Mo FK, Zhong DF. Investigation of microemulsion system for transdermal delivery of meloxicam. Int J Pharm 2006;321:117–23. 41. Priya Moulik S, Kumar Rakshit A. Physicochemisty and applications of micro- emulsions. J Surf Sci Technol 2006;22:159–86. 42. Sabri LA, Sulaiman HT, Khalil YI. An Investigation release and rheological properties of miconazole nitrate from emulgel and introduction. Iraqi J Pharm Sci 2009;18:26–31. 43. Li C, Liu C, Liu J, Fang L. Correlation between rheological properties, in vitro release, and percutaneous permeation of tetrahydropalmatine. AAPS PharmSciTech 2011;12:1002–10. 44. Coviello T, Matricardi P, Alhaique F, Farra R, Tesei G, Fiorentino S, Asaro F, Milcovich G, Grassi M. Guar gum / borax hydrogel : Rheological , low field NMR and release characterizations. eXPRESS Polym Lett 2013;7:733–46. 45. Costa P, Sousa Lo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123–33.
Year 2017,
Volume: 21 Issue: 3, 688 - 700, 24.06.2017
Abstract
References
- 1. Jain A, Jain S, Rawat S. Emerging fungal infections among children: A review on its clinical manifestations, diagnosis, and prevention. J Pharm Bioallied Sci 2010;2:314–20. 2. Chudasama A, Patel V, Nivsarkar M, Vasu Kamala. Investigation of microemulsion system for transdermal delivery of Itraconazole. J Adv Pharm Technol Res 2011;2:30–8. 3. Alam S, Iqbal Z, Ali A, Khar RK, Ahmad FJ, Akhter S, Talegaonkar S. Microemulsion as a potential transdermal carrier for poorly water soluble antifungal drug itraconazole. J Dispers Sci Technol. 2009;31:84–94. 4. Kumar N, Shishu. D-optimal experimental approach for designing topical microemulsion of itraconazole: Characterization and evaluation of antifungal efficacy against a standardized Tinea pedis infection model in Wistar rats. Eur J Pharm Sci 2015;67:97–112. 5. Grant SM, Clissold SP. Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses. Drugs 1989;37:310–44. 6. Ambala R, Vemula SK. Formulation and characterization of ketoprofen emulgels. J Appl Pharm Sci 2015;5:112–7. 7. Mohamed MI. Optimization of chlorphenesin emulgel formulation. AAPS J 2004;6:e26. 8. Khunt DM, Mishra AD, Shah DR. Formulation design & development of piroxicam emulgel. Int J PharmTech Res 2012;4:1332–44. 9. Karasulu HY. Microemulsions as novel drug carriers : the formation , stability , applications and toxicity. Expert Opin Drug Deliv 2008;5:119–36. 10. Shah VV, Sharma M, Gandhi K, Suthar V, Parikh RK. Quality by Design (QbD) approach for optimization of microemulsion based topical gel. Marmara Pharm J 2016;20:415–24. 11. Mali KK, Dhawale SC. Design and optimization of modified tamarind gum-based floating-bioadhesive tablets of verapamil hydrochloride. Asian J Pharm 2016;10:2–8. 12. Boonme P, Kaewbanjong J, Sangduangyang S, Suksawat S, Teeranachaideekul V. Microemulsion-based hydrogels of itraconazole: Evaluation of characteristics and stability. Asian J Pharm Sci 2016;11:98–9. 13. Shahin M, Hady SA, Hammad M, Mortada N. Novel jojoba oil-based emulsion gel formulations for clotrimazole delivery. AAPS PharmSciTech 2011;12:239–47. 14. Fouad SA, Basalious EB, El-Nabarawi MA, Tayel SA. Microemulsion and poloxamer microemulsion-based gel for sustained transdermal delivery of diclofenac epolamine using in-skin drug depot: In vitro/in vivo evaluation. Int J Pharm 2013;453:569–78. 15. Goyal P, Kumar V, Sharma P. Carboxymethylation of Tamarind kernel powder. Carbohydr Polym 2007;69:251–5. 16. Shaw GS, Uvanesh K, Gautham SN, Singh V, Pramanik K, Banerjee I, Kumar N, Pal K. Development and characterization of gelatin-tamarind gum/carboxymethyl tamarind gum based phase-separated hydrogels:a comparative study. Des Monomers Polym 2015;18:434–50. 17. Kaur G, Jain S, Tiwary AK. Chitosan-carboxymethyl tamarind kernel powder interpolymer complexation: Investigations for colon drug delivery. Sci Pharm 2010;78:57–78. 18. Pal S, Sen G, Mishra S, Dey RK, Jha U. Carboxymethyl tamarind: Synthesis, characterization and its application as novel drug-delivery agent. J Appl Polym Sci 2008;110:392– 400. 19. Kaur H, Ahuja M, Kumar S, Dilbaghi N. Carboxymethyl tamarind kernel polysaccharide nanoparticles for ophthalmic drug delivery. Int J Biol Macromol 2012;50:833–9. 20. Madgulkar AR, Bhalekar MR, Padalkar RR, Shaikh MY. Optimization of carboxymethyl-xyloglucan-based tramadol matrix tablets using simplex centroid mixture design. J Pharm 2013;2013:1–11. 21. Datta R, Bandyopadhyay AK. A new nasal drug delivery system for diazepam using natural mucoadhesive polysaccharide obtained from tamarind seeds. Saudi Pharm J 2006;14:115–9. 22. Mali K, Dhawale S, Dias R, Havaldar V, Ghorpade V, Salunkhe N. Nasal mucoadhesive in situ gel of granisetron hydrochloride using natural polymers. J Appl Pharm Sci 2015;5:084–93. 23. Ghelardi E, Tavanti A, Davini P, Celandroni F, Salvetti S, Parisio E, Boldrini E, Senesi S, Campa M. A mucoadhesive polymer extracted from tamarind seed improves the intraocular penetration and efficacy of rufloxacin in topical treatment of experimental bacterial keratitis. Antimicrob Agents Chemother 2004;48:3396-401. 24. Avachat AM, Gujar KN, Wagh KV. Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate. Carbohydr Polym 2013;91:537–42. 25. Hou P, Cao S, Ni J, Zhang T, Cai Z, Liu J, Wang Y, Wang P, Lei H, Liu Y. In-vitro and in-vivo comparison of T-OA microemulsions and solid dispersions based on EPDC. Drug Dev Ind Pharm 2015;41:263–71. 26. Barot BS, Parejiya PB, Patel HK, Mehta DM, Shelat PK. Microemulsion-based antifungal gel delivery to nail for the treatment of onychomycosis: Formulation, optimization, and efficacy studies. Drug Deliv Transl Res 2012;2:463–76. 27. Kumar M, Pathak K, Misra A. Formulation and characterization of nanoemulsion-based drug delivery system of risperidone. Drug Dev Ind Pharm 2009;35:387–95. 28. Hong JY, Kim JK, Song YK, Park JS, Kim CK. A new selfemulsifying formulation of itraconazole with improved dissolution and oral absorption. J Control Release 2006;110:332–8. 29. Kumar R, Sinha VR. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surfaces B Biointerfaces 2014;117:82–8. 30. López-Cervantes M, Escobar-Chávez JJ, Casas-Alancaster N, Quintanar-Guerrero D, Ganem-Quintanar A. Development and characterization of a transdermal patch and an emulgel containing kanamycin intended to be used in the treatment of mycetoma caused by Actinomadura madurae. Drug Dev Ind Pharm 2009; 35:1511–21. 31. Khalil YI, Khasraghi AH, Mohammed EJ. Preparation and evaluation of physical and rheological properties of clotrimazole emulgel. Iraqui J Pharm Sci 2011;20:19–27. 32. Shen Y, Ling X, Jiang W, Du S, Lu Y, Tu J. Formulation and evaluation of Cyclosporin A emulgel for ocular delivery. Drug Deliv 2015;22:911-7. 33. Bachhav YG, Patravale VB. Formulation of meloxicam gel for topical application: In vitro and in vivo evaluation. Acta Pharm 2010;60:153–63. 34. Thakur NK, Bharti P, Mahant S, Rao R. Formulation and characterization of benzoyl peroxide gellified emulsions. Sci Pharm 2012;80:1045–60. 35. Naga Sravan Kumar Varma V, Maheshwari P V, Navya M, Reddy SC, Shivakumar HG, Gowda DV. Calcipotriol delivery into the skin as emulgel for effective permeation. Saudi Pharm J 2014;22:591-9. 36. Ismail A, Saleh KI, Ibrahim MA, Khalaf S. Effect of porous silica as a drug carrier on the release rate of naproxen from emulgel. Bull Pharm Sci 2006;29:224–35. 37. Wagh VD, Deshmukh OJ. Itraconazole niosomes drug delivery system and its antimycotic activity against Candida albicans. ISRN Pharm 2012;2012:Article ID 653435. 38. Üstündağ Okur N, Çağlar EŞ, Arpa MD, Karasulu HY. Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine. Pharm Dev Technol 2016;7450:1–11. 39. Bachhav YG, Patravale VB. Microemulsion based vaginal gel of fluconazole: Formulation, in vitro and in vivo evaluation. Int J Pharm 2009;365:175–9. 40. Yuan Y, Li SM, Mo FK, Zhong DF. Investigation of microemulsion system for transdermal delivery of meloxicam. Int J Pharm 2006;321:117–23. 41. Priya Moulik S, Kumar Rakshit A. Physicochemisty and applications of micro- emulsions. J Surf Sci Technol 2006;22:159–86. 42. Sabri LA, Sulaiman HT, Khalil YI. An Investigation release and rheological properties of miconazole nitrate from emulgel and introduction. Iraqi J Pharm Sci 2009;18:26–31. 43. Li C, Liu C, Liu J, Fang L. Correlation between rheological properties, in vitro release, and percutaneous permeation of tetrahydropalmatine. AAPS PharmSciTech 2011;12:1002–10. 44. Coviello T, Matricardi P, Alhaique F, Farra R, Tesei G, Fiorentino S, Asaro F, Milcovich G, Grassi M. Guar gum / borax hydrogel : Rheological , low field NMR and release characterizations. eXPRESS Polym Lett 2013;7:733–46. 45. Costa P, Sousa Lo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123–33.
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Details
| Subjects | Health Care Administration |
|---|---|
| Journal Section | Articles |
| Authors | |
| Publication Date | June 24, 2017 |
| Published in Issue | Year 2017 Volume: 21 Issue: 3 |