Formulation and development of vaginal films of poorly water soluble drug, metronidazole, using mixed solvency concept and their evaluations
Novel application of Mixed solvency in development of vaginal films
Aim: To deliver antibacterial therapy in an efficacious way, film dosage form has been proposed for drug delivery in vagina which can overcome bioavailability issues of poorly water soluble drugs. The present research work is aimed to explore the application of mixed solvency concept to increase solubility of poorly water soluble drug, metronidazole. Materials and Methods: Metronidazole, a slightly soluble drug in water was tried to be solubilized by employing the combination of solubilizers like niacinamide, sodium benzoate, sodium caprylate, caffeine and urea to endeavour its fast dissolving film formulations. The procured sample of drug was characterized by UV, IR and DSC studies. The formulations were evaluated for various properties of film such as thickness, folding endurance, surface pH, disintegration time and thin layer chromatography. Stability studies of vaginal films of metronidazole were performed for ten weeks at room temperature, and refrigerated conditions. Results and Discussion: It was found that 97.54% and 97.58% of drug was remaining after stability study at respective temperatures in batch F1 and 98.53% and 96.57% in batch F4.Conclusion: It was concluded that the approach of mixed solvency concept is novel, safe, cost-effective and user friendly. It also eliminates the problem of toxicity associated with high concentration of water-soluble solubilizers. So, it may be employed in dosage form development of drugs with poor solubility to overcome bioavailability issues.
Keywords: Solubility, metronidazole, vaginal films, mixed solvency concept.
2. Mastromarino P et al, Bacterial vaginosis: a review on clinical trials with probiotics. New Microbial, 2013; 36(3):229-38.
3. Eschenbach DA et al, Diagnosis and clinical manifestations of bacterial vaginosis. Jornal of Obstetrics and Gynaecology, 1988; 158(4):819-28.
4. Dharmik PG et al, Susceptibility pattern of various azoles against candida species causing vulvovaginal candidiasis. Journal of Obstetrics and Gynaecology of India, 2013; 63(2): 135-137.
5. Ness RB et al, Bacterial vaginosis and risk of pelvic inflammatory disease. Obstet Gynecol, 2004; 104(4):761-769.
6. Johnson TA et al, The effect of pH on release of PGE2 from vaginal and endocervical preparations for induction of labour: an in- vitro study. British Journal of Obstetrics and Gynaecology, 1992; 99(11):877-880.
7. Borumand M et al, Development and in vitro evaluation of a novel contraceptive vaginal mucoadhesive propanolol hydrochloride film. Journal of drug delivery science and technology, 2014; 24(6):637-644.
8. Bassi P et al, Polymeric films as a promising carrier for bioadhesive drug delivery: development, characterization and optimization. Saudi Pharmaceutical Journal, 2017; 25(1):32-43.
9. Sudeendra RB. Development and characterization of bioadhesive vaginal films of clotrimazole for vaginal candidiasis. Vol. 52. 2010.
10. Dobariar NB et al, A novel itraconazole bioadhesive film for vaginal delivery: design, optimization, and physicodynamic characterization. AAPS PharmSciTech, 2009; 10(3): 951.
11. Ibrahim A et al, Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulation for vaginal application. Acta Pharm, 2012; 62:59-70
12. Gupta H et al, Ion activated bioadhesive in situ gel of clindamycin for vaginal application. International journal of drug delivery, 2009; 1:32-40.
13. Zhang W et al, Development of a vaginal delivery film containing EFdA, a novel anti- HIV nucleoside reverse transcriptase inhibitor. Int. J Pharm, 2014; 461(0): 203-213.
14. Maheshwari RK, "Mixed-Solvency" – A novel concept for solubilization of poorly water-soluble drugs, Journal of Technology and Engineering Sciences, 2009; 1 (1):39-44.
15. Maheshwari RK Solubilization of Ibuprofen by Mixed-Solvency Approach, The Indian Pharmacist, 2009; 8 (87):81-84.
16. Maheshwari RK, Potentiation of solvent character by mixed-solvency concept: A novel concept of solubilization, Journal of Pharmacy Research, 2010; 3 (2):411-413.
17. Maheshwari RK, Upadhyay N, Jain J, Patani M, Mathuria KC, New spectrophotometric estimation of naproxen tablets formulations employing mixed solvency concept (at 331nm), International Journal of Pharmacy & Technology, 2011; 3 (4):3618-3621.
18. Maheshwari RK, Fouzdar A, “Solid as solvent”- Novel spectrophotometric analytical technique for ornidazole tablets using solids (eutectic liquid of phenol and niacinamide) as solubilizing agents (mixed solvency concept), Indian Drugs, 2015; 52(06): 42-45.
19. Maheshwari RK, Singh S, George P, Fouzdar A, “Solid as solvent”- novel spectrophotometric analytical technique for satranidazole tablets using solids (eutectic liquid of phenol and niacinamide) as solubilizing agents (mixed solvency concept), International Journal of Innovative Research in Pharmaceutical Sciences, 2015; 1(1): 26-29.
20. Jain DK, Patel VK, Bajaj S, Jain N, Maheshwari RK, Novel approach for spectrophotometric estimation of solid dosage forms of tinidazole using solids (eutectic liquid of phenol and niacinamide) as solubilizing agent (mixed solvency concept), World Journal of Pharmacy and Pharmaceutical Sciences, 2015; 4(04):763-769.
21. Jain S et al, Simultaneous estimation of norfloxacin and tinidazole in solid dosage form by uv-spectrophotometry using mixed solvency concept, World Journal of Pharmaceutical and Medical Research, 2018, 4(1):112-117.
22. Maheshwari RK et al; “Solid as solvent”- Novel spectrophotometric analytical method for quantitative estimation of gatifloxacin tablets using solids (eutectic liquid of phenol and lignocaine hydrochloride) as solubilizing agents (mixed solvency concept), European Journal of Biomedical and Pharmaceutical Sciences, 2017; 4(8):644-648.
23. Maheshwari RK, Dahima R, “Solid as solvent”- Novel spectrophotometric analytical technique for quantitative estimation of tinidazole in tablets using solids (eutectic liquid of phenol and lignocaine hydrochloride) as solubilizing agents (mixed solvency concept), Journal of Drug Delivery and Therapeutics, 2017; 7(3):127-130.
24. Rajagopalan R, Formulation and evaluation of tinidazole syrup made by mixed solvency concept, Scholars Research Library, 2012; 4 (1):170-174.
25. Jain R, Maheshwari RK, George P, Formulation development and evaluation of controlled release tablets of lamotrigine using mixed solvency concept, Bulletin of Pharmaceutical Research, 2015; 5(1):9-14.
26. Maheshwari RK, Gupta P, Gupta H, Formulation development of a model dry injection for reconstitution of poorly water soluble drug ornidazole using mixed solvency concept and its evaluation, International Journal of Science and Research, 2018; 7(4):408-414.
27. Padiyar A, Maheshwari RK; Novel dry injection for reconstitution of aspirin using solid solubilizers, Journal of Drug Delivery and Therapeutics, 2017; 7(7):44-45. https://doi.org/10.22270/jddt.v7i7.1582
28. Patel SK, Maheshwari RK, Formulation development and evaluation of SEDDS of poorly soluble drug made by novel application of mixed-solvency concept, International Journal of Pharmaceutical Research, 2012; 4:51-56.
29. Shilpkar R, Maheshwari RK, Formulation development and evaluation of injection of poorly soluble drug using mixed solvency concep, International Journal of Pharma and Bio Sciences, 2012; 3:179-189.
30. Solanki SS, Soni LK, Maheshwari RK, Study on mixed solvency concept in formulation development of aqueous injection of poorly water soluble drug, Journal of Pharmaceutics, 2013; 4(2):58-61.
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