QUALITY BY DESIGN APPROACH FOR DEVELOPMENT AND OPTIMIZATION OF NITRENDIPINE LOADED NIOSOMAL GEL FOR ACCENTUATED TRANSDERMAL DELIVERY
Objective: The purpose of the present investigation was to develop and optimize nitrendipine loaded niosomal gel for transdermal delivery using quality by design approach.
Methods: Niosomal formulations were developed by application of the thin-film hydration method using different ratios of span 60, cholesterol, temperature, and optimized by three factors-three levels Box-Behnken statistical design. The independent variables were non-ionic surfactant, cholesterol, and temperature, while vesicle size, polydispersity index, and entrapment efficiency were dependent variables. The nitrendipine loaded optimized formulation was incorporated into gel and evaluated for in vitro release, ex-vivo skin permeation, confocal laser scanning microscopy, and histopathological studies.
Results: The optimized formulation showed the vesicular size of 226.1±4.36 nm, polydispersity index of 0.282±0.012, and entrapment efficiency of 95.34±3.18% with spherical morphology. The optimized niosomal gel formulation showed transdermal flux 127.60 µg/cm2h through albino Wistar rat skin. Niosomal gel was proved significantly superior by confocal laser scanning microscopy for satisfactory permeation and distribution of gel, deep into the rat skin. Furthermore, dermal safety was confirmed by histopathological studies for transdermal application.
Conclusion: It was concluded that the developed niosomal gel overcomes the limitation of low penetration through rat skin and could be a potential nano vesicular system for transdermal delivery.
2. Anchala R, Kannuri NK, Pant H, Khan H, Franco OH, Angelantonio ED, et al. Hypertension in India: a systematic review and meta-analysis of prevalence, awareness, and control of hypertension. J Hypertension 2014;32:1170-7.
3. Kepekci Tekkeli SE. Development of an HPLC-UV method for the analysis of drugs used for combined hypertension therapy in pharmaceutical preparations and human plasma. J Anal Methods Chem 2013:1-10. https://doi.org/10.1155/2013/ 179627.
4. Singh S, Shankar R, Singh GP. Prevalence and associated risk factors of hypertension: a cross-sectional study in urban Varanasi. Int J Hypertension 2017:1-10. DOI:10.1155/ 2017/5491838
5. Badyal DK, Lata H, Dadhich AP. Animal model of hypertension and effect of drugs. Indian J Pharmacol 2003;35:349-62.
6. Freeman AJ, Vinh A, Widdop RE. Novel approaches for treating hypertension. F1000 Res 2017;6:80.
7. Rossouw DS, Luus HG. Evaluation of nitrendipine channel blocker-new calcium channel blocker. South Afr Med J 1991;79:379-81.
8. Goa KL, Sorkin EM. Nitrendipine a review of its pharmacodynamics and pharmacokinetic properties and therapeutic efficacy in the treatment of hypertension. Drugs 1987;33:123-55.
9. Shang D, Wang X, Zhao X, Huang F, Tian G, Lu W, et al. Simultaneous determination of nitrendipine and hydrochlorothiazide in spontaneously hypertensive rat plasma using HPLC with on-line solid-phase extraction. J Chromato B 2011;879:3459-64.
10. Venishetty VK, Durairaj C, Sistla R, Yamsani MR, Diwan PV. Development and validation of a reversed-phase HPLC method for determination of nitrendipine in rat plasma: application to pharmacokinetic studies. Bio Chromato 2007;21:363-8.
11. Ahad A, Shakeel F, Raish M, Al-Jenoobi FI, Al-Mohizia AM. Solubility and thermodynamic analysis of antihypertensive agent nitrendipine in different pure solvents at the temperature range of 298.15-318.15° k. AAPS PharmSciTech 2017;18:2737-43.
12. Tipre DN, Vavia PR. Acrylate-based transdermal therapeutic system of nitrendipine. Drug Dev Indus Pharm 2003;29:71-8.
13. Mittal A, Sara US, Ali A, Mohammed A. Design, development, physicochemical, in vitro and in vivo evaluation of monolithic matrix type transdermal patches containing nitrendipine. Pharm Dev Tech 2009;14:422-34.
14. Jain R, Patravale VB. Development and evaluation of nitrendipine nanoemulsion for transdermal drug delivery. J Biom Nanotech 2009;5:62-8.
15. Bhaskar K, Mohan CK, Lingam M, Mohan SJ, Venkateshwarlu V, Rao YM, et al. Development of SLN and NLC enriched hydrogels for transdermal delivery of nitrendipine: in vivo and in vitro characteristics. Drug Dev Ind Pharm 2009;35:98-113.
16. Xia D, Quan P, Piao H, Sun S, Yin Y, Cui F. Preparation of stable nitrendipine nanosuspension using the precipitation–ultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci 2010;40:325-34.
17. Cui F, Yang M, Jiang Y, Cun D, Lin W, Fan Y, et al. Design of sustain-release nitrendipine microsphere having solid dispersion structure by quasi emulsion solvent diffusion method. J Controlled Release 2003;91:375-84.
18. Moghassemi S, Hadjizadeh A. Nano-niosomes as nano-scale drug delivery systems: an illustrated review. J. Controlled Release 2014;185:22-36.
19. Sharma D, Ali AA, Aate JR. Niosomes as novel drug delivery system: review article. Pharm Tutor 2018;6:58-65.
20. Kumar BS, Krishna R, Lakshmi PS, Vasudev DT, Nair SC. Formulation and evaluation of niosomal suspension of cefixime. Asian J Pharm Clin Res 2017;10:194-201.
21. Chen S, Hanning S, Falconer J, Locke M, Wen J. Recent advances in non-ionic surfactant vesicles (niosomes): fabrication, characterization, pharmaceutical and cosmetic applications. Eur J Pharm Biopharm 2019;144:18-39.
22. Hirva S, Jenisha P. Bicelle: a lipid nanostructure for transdermal delivery. J Crit Rev 2016;3:17-22.
23. Seleci DA, Seleci M, Walter JG, Stahl F, Scheper T. Niosomes as nano-particular drug carriers: fundamentals and recent applications. J Nanomat 2016;1-13. https://doi.org/ 10.1155/2016/7372306
24. El-Ridy MS, Yehia SA, Mohsen AM, El-Awdan SA, Darwish AB. Formulation of niosomal gel for enhanced transdermal lornoxicam delivery: in vitro and in vivo evaluation. Curr Drug Delivery 2018;15:122-33.
25. Azeem A, Anwer MK, Telegaonkar S. Niosomes in sustained and targeted drug delivery: some recent advances. J Drug Target 2009;17:671-89.
26. Patel KK, Kumar P, Thakkar HP. Formulation of niosomal gel for enhanced transdermal lopinavir delivery and its comparative evaluation with ethosomal gel. AAPS PharmSciTech 2012;13:1502-10.
27. Qumber M, Ameeduzzafar, Imam SS, Ali J, Ahmed J. Formulation and optimization of lacidipine loaded niosomal gel for transdermal delivery: in vitro characterization and in vivo activity. Biomed Pharmacol 2017;93:255-66.
28. Ferreira SL, Bruns RE, Ferreira HS, Matos GD, David JM, Brandao GC, et al. Box-behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta 2007;597:179-86.
29. Singh B, Kapil R, Nandi M, Ahuja N. Developing oral drug delivery systems using formulation by design: vital precepts, retrospect and prospects. Expert Opin Drug Delivery 2011;8:1341-60.
30. Amir BA, Pougnet P, Hami AE. Metamodel development, embedded mechatronic systems. 1st Edition. Vol. 2; 2015. p. 151-79.
31. Aquil M, Kamran M, Ahad A, Imam SS. Development of clove oil based nanoemulsion of olmesartan for transdermal delivery: box-behnken design optimization and pharmacokinetic evaluation. J Mol Liquids 2016;214:238-48.
32. Aboelwafa AA, El-Setouhy DA, Elmeshad AN. Comparative study on the effects of some polyoxyethylene alkyl ether and sorbitan fatty acid ester surfactants on the performance of transdermal carvedilol proniosomal gel using experimental design. AAPS PharmSciTech 2010;11:1591-602.
33. Tavano L, Gentile L, Rossi CO, Muzzalupo R. Novel gel-niosomes formulations as multi-component systems for transdermal drug delivery. Colloids Surf B 2013;110:281-8.
34. Ali M, Motaal AA, Ahmed MA, Alsayri A, El-Gazayerly ON. An in vivo study of hypericum perforatum in a niosomal topical drug delivery system. Drug Delivery 2018;25:417-25.
35. Asthana GS, Asthana A, Singh D, Sharma PK. Etodolac containing topical niosomal gel: formulation development and evaluation. J Drug Delivery 2016;2016:1-8.
36. Shivhare UD, Wasnik SV. Formulation development and evaluation of niosomal gel for transdermal delivery of an antihypertensive drug. Int J Biopharm 2013;4:231-8.
37. Ramadan AA, Elbakry AM, Esmaeil AH, Khaleel SA. Pharmaceutical and pharmacokinetic evaluation of novel rectal mucoadhesive hydrogels containing tolmetin sodium. J Pharma Invest 2018;48:673-83.
38. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery system. Acta Poloniae Pharma Drug Res 2010;67:217-23.
39. Higuchi T. Mechanism of sustained-action medication theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 1963;52:1145.
40. Gouda R, Baishya H, Qing Z. Application of mathematical models in drug release kinetics of carbidopa and levodopa ER tablets. J Dev Drugs 2017;6:1-8.
41. Maghraby GM, Ahmed AA, Osman MA. Penetration enhancers in pro-niosomes as a new strategy for enhanced transdermal drug delivery. Saudi Pharma J 2015;23:67-74.
42. Ahad A, Saleh AA, Mohizea AM, Jenoobi FI, Raish M, Yassin AE, et al. Formulation and characterization of novel soft nano-vesicles for enhanced transdermal delivery of eprosartan mesylate. Saudi Pharma J 2017;25:1040-6.
43. Ahad A, Aquil M, Kohli K, Sultana Y, Mujeeb M, Ali A. Formulation and optimization of nanotransfersomes using experimental design technique for accentuated transdermal delivery of valsartan. Nanomed: Nanotechnol Biol Med 2012;8:237-49.
44. Mauko A, Muck T, Mirtic B, Mladenovic A, Kreft M. Use of confocal laser scanning microscopy (CLSM) for the characterization of porosity in marble. Mat Characterization 2009;60:603-9.
45. Pathan IB, Jaware BP, Shelke S, Ambekar W. Curcumin loaded ethosomes for transdermal application: formulation, optimization, in vitro and in vivo study. J Drug Delivery Sci Tech 2018;44:49-57.
46. Mohawed OM, El-Ashmoony MM, Elgazayerly ON. Niosome encapsulated clomipramine for transdermal controlled delivery. Int J Pharm Pharm Sci 2014;6:567-75.
47. Thorat YS, Kote NS, Patil VV, Hosmani AH. Formulation and evaluation of liposomal gel containing extract of piprine. Int J Curr Pharm Res 2020;12:126-9.
48. Ubaidulla U, Reddy M, Rukmani K, Ahmed FJ, Kher RK. Transdermal therapeutic system of carvedilol: effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics. AAPS PharmSciTech 2007;8:13-20.
49. Kapoor K, Pandit V, Nagaich U. Development and characterization of sustained-release methotrexate loaded cubosomes for topical delivery in rheumatoid arthritis. Int J Appl Pharm 2020;12:33-9.
50. Khan R, Irchhaiya R. In vitro in vivo evaluation of niosomal formulation of famotidine. Int J Pharm Pharm Sci 2020;12:15-22.
This work is licensed under a Creative Commons Attribution 4.0 International License.