Research Journal of Pharmacy and Technology

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Solid Dispersion Technique for Solubility Improvement of Ketoconazole for Vaginal Delivery


Affiliations
1 Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India
     

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The activity of any drug depends on bioavailability of drug. As biological barriers permit only dissolved molecules, it is essential to have sufficient solubility in biological fluid. Vaginitis is a very common gynecological problem in women of all age groups and mostly indicated as mixed vaginal infection. Ketoconazole is a topical antifungal drug used to treat vaginitis and has poor solubility (BCS class- II). In the present study, an attempt has been made to improve the solubility of ketoconazole by solid dispersions (SD) prepared by kneading and spray drying techniques using hydrophilic carrier; Soluplus, Poloxamer 188 and β-cyclodextrin. The SD prepared by soluplus with spray drying method exhibited higher solubility than those prepared by kneading method. SD was further characterized by FTIR, DSC, and XRD analysis. Fourier transform infrared spectroscopy study confirmed the formation of SD complex of ketoconazole and soluplus. Polymer entrapped the drug and formed amorphous state which was confirmed by DSC studies. The surface morphology of the SD by X-ray diffraction confirmed conversion of drug from crystalline form to amorphous. Conclusively, Soluplus looks to be a promising carrier to improve the solubility of poorly soluble drugs.

Keywords

Solid Dispersions, Kneading, Spray-Drying, Ketoconazole, Soluplus, Poloxamer 188, Β-cyclodextrin.
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  • Hill GB. The microbiology of bacterial vaginosis. American Journal of Obstetrics and Gynecology. 1993; 169:450-454.

  • Kent HL. Epidemiology of vaginitis. American Journal of Obstetrics and Gynecology. 1991; 165:1168-1176.

  • Najmuddin M, Khan T, Mohsin AA, Shelar S and Patel V. Enhancement of dissolution rate of ketoconazole by solid dispersion technique. International Journal of Pharmacy and Pharmaceutical Sciences. 2010; 2:131-136.

  • Sobel JD. Vaginitis. The New England Journal of Medicine. 1997; 337:1896-1903.

  • Deshkar SS. Patil AT. Development of mucoadhesive gel of fluconazole for vaginal candidiasis. Indo Am. J. Pharm. Res. 2015; 5(11):3599-3610.

  • Deshkar SS. Patil AT. Development of mucoadhesive gel of fluconazole for vaginal candidiasis. Indo American Journal of Pharmaceutical Research. 2015; 5(11):3599-3610.

  • Dattatreya B Udgirkar, SN Hiremath, K Sreenivasa Rao, Dilip Pawar. Formulation and In-vitro Evaluation of Buccoadhesive Tablets containing Ketoconazole inclusion complex with β- Cyclodextrin. Research Journal of Pharmacy and Technology. 2009; 2(2):396-404.

  • Keerthi Manukonda, Rama Rao N, Santhosh Aruna M, Lakshmi Prasanna J. Solid Dispersions-An Approach to Enhance the Dissolution Rate of Clopidogrel Bisulphate. Asian Journal of Pharmaceutical Sciences. 2014; 4(4):165-168.

  • Wu C, Williams RO, Donnell KO, Dong Y, Lang B, Li H, Zhang H, Zhang M, Wang Z. Formulation and delivery of improved amorphous fenofibrate solid dispersion prepared by thin film freezing. European Journal of Pharmaceutics and Biopharmaceutics. 2012; 82:534–544.

  • Vaibhav A. Jagtap, Ajay N. Talele, Atul R.Bendale, Sachin Narkhede, Anil Jadhav, G. Vidyasagar. Solubility Enhancement of Pioglitazone by Using Poloxamer (188 and 407) with the Help of Kneading Method. Research Journal of Pharmacy and Technology.2010; 3(4):1152-1157.

  • Das SK, Nanda A, Khanam J, Yuvaraja K, Roy S. Solid dispersions: an approach to enhance the bioavailability of poorly water soluble drugs. International Journal of Psychology. 2012; 1:37–46.

  • Trivedi RV, Admane PS, Taksande JB, Mahore JG, Umekar MJ. Solubility enhancement studies of hydrochlorothiazide by preparing solid dispersions using losartan potassium and urea by different methods. Scholars Research Library. Der Pharmacia Lettre. 2011; 3(6):8-17.

  • Tawfique K, Danesment TK, Warnock DW. Clinical pharmacokinetics of ketoconazole. International Journal of Clinical Pharmacology Research. 1988; 14:13–14.

  • AV Yadav, VB Yadav. Improvement of Physicochemical properties of Mesalamine with Hydrophilic Carriers by Solid Dispersion (kneading) method. Research Journal of Pharmacy and Technology. 2008; 1(4):422-425.

  • DS Saindane, AS Kulkarni, AN Sagri, RB Pimprikar, SB Yeshwante, CP Suryawanshi, SD Firke, MK Kale. Physicochemical Characterization of Solid Dispersion of Cefexime with Poloxamer 188. Research Journal of Pharmacy and Technology Research. 2009; 1(2): 162-166.

  • Connors HK. Phase solubility techniques. Adv. Chem. Phys. Advances. 1965; 4:117–212.

  • Hardung H, Djuric D. Combining SA. HME and solubilization: Soluplus -The solid solution. Drug Delivery Technology. 2010; 10:20–27.

  • Tushar D. Sonawane, Rajesh Z. Mujoriya. Role of Hydrophilic Carrier in Solubility Enhancement. Research Journal of Pharmacy and Technology. 2016; 8(3): 173-176.


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  • Solid Dispersion Technique for Solubility Improvement of Ketoconazole for Vaginal Delivery

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Authors

J. G. Mahore
Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India
S. S. Deshkar
Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India
P. P. Kumare
Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India

Abstract


The activity of any drug depends on bioavailability of drug. As biological barriers permit only dissolved molecules, it is essential to have sufficient solubility in biological fluid. Vaginitis is a very common gynecological problem in women of all age groups and mostly indicated as mixed vaginal infection. Ketoconazole is a topical antifungal drug used to treat vaginitis and has poor solubility (BCS class- II). In the present study, an attempt has been made to improve the solubility of ketoconazole by solid dispersions (SD) prepared by kneading and spray drying techniques using hydrophilic carrier; Soluplus, Poloxamer 188 and β-cyclodextrin. The SD prepared by soluplus with spray drying method exhibited higher solubility than those prepared by kneading method. SD was further characterized by FTIR, DSC, and XRD analysis. Fourier transform infrared spectroscopy study confirmed the formation of SD complex of ketoconazole and soluplus. Polymer entrapped the drug and formed amorphous state which was confirmed by DSC studies. The surface morphology of the SD by X-ray diffraction confirmed conversion of drug from crystalline form to amorphous. Conclusively, Soluplus looks to be a promising carrier to improve the solubility of poorly soluble drugs.

Keywords


Solid Dispersions, Kneading, Spray-Drying, Ketoconazole, Soluplus, Poloxamer 188, Β-cyclodextrin.

References