NANOSPHERE-LOADED TADALAFIL WITH ENHANCED ORAL BIOAVAILABILITY: INNOVATIVE APPLICATION OF ELECTROHYDRODYNAMIC TECHNIQUE
DOI:
https://doi.org/10.22159/ijcpr.2020v12i1.36828Keywords:
Dissolution enhancement, Electrohydrodynamic atomization, Tadalafil, Nanoparticles, NanosphereAbstract
Objective: Electrohydrodynamic atomization is a technique that utilizes electrical potential differences for the fabrication of particles ranging from nano to micrometer size, where the ultra-charged droplets of drug-loaded mist deposit as nanospheres after solvent evaporation. The drug-loaded polymeric spherical nanocomposites have a small volume with large surface area, which is a beneficial characteristic for dissolution and bioavailability enhancement of class II drugs.
Methods: This facile approach is employed for the preparation of tadalafil-loaded nanosystems, a class II drug used for erectile dysfunction treatment. Tadalafil-loaded nanoparticles prepared with different polymer concentrations were evaluated through process yield, drug loading, morphology and functional performance. Further, drug solid-state and compatibility of formulation components were assessed.
Results: The results obtained pointed out that nanoparticles were of uniform spherical morphologies with a size range between 1279±141 and 374±13 nm. The system maintained a high loading efficacy of 88%, with most of the loaded drug released within 2 min during the in vitro dissolution studies. The differential scanning calorimetry, X-ray diffraction and Fourier-transform infrared spectroscopy demonstrated the presence of tadalafil in an amorphous form or as a molecular dispersion within the polymer matrix.
Conclusion: Tadalafil-loaded nanoparticles manufactured through this methodology is qualified as a strategy to ameliorate its solubility and bioavailability.
Downloads
Download data is not yet available.
References
1. Gomez Estaca J, Balaguer MP, Gavara R, Hernandez Munoz P. Formation of zein nanoparticles by electrohydrodynamic atomization: effect of the main processing variables and suitability for encapsulating the food coloring and active ingredient curcumin. Food Hydrocoll 2012;28:82–91.
2. Bohr A, Kristensen J, Dyas M, Edirisinghe M, Stride E. Release profile and characteristics of electrosprayed particles for oral delivery of a practically insoluble drug. J R Soc Interface 2012;9:2437–49.
3. Xie J, Marijnissen JCM, Wang CH. Microparticles developed by electrohydrodynamic atomization for the local delivery of an anticancer drug to treat C6 glioma in vitro. Biomaterials 2006;27:3321–32.
4. Zolkepali NK, Abu bakar NF, Naim MN, Anuar N, Kamalul Aripin NF, Abu Bakar MR, et al. Formation of fine and encapsulated mefenamic acid form I particles for dissolution improvement via electrospray method. Part Sci Technol 2018;36:298–307.
5. Vemula VR, Lagishetty V, Lingala S. Solubility enhancement techniques. Int J Pharm Sci Rev Res 2010;5:41–51.
6. Yu H, Teo J, Chew JW, Hadinoto K. Dry powder inhaler formulation of high-payload antibiotic nanoparticle complex intended for bronchiectasis therapy: spray drying versus spray freeze drying preparation. Int J Pharm 2016;499:38–46.
7. Das S, Banerjee R, Bellare J. Aspirin loaded albumin nanoparticles by coacervation: implications in drug delivery. Trends Biomater Artif Organs 2005;18:203–12.
8. Kwon HY, Lee JY, Choi SW, Jang Y, Kim JH. Preparation of PLGA nanoparticles containing estrogen by an emulsification-diffusion method. Colloids Surf A 2001;182:123–30.
9. Desgouilles S, Vauthier C, Bazile D, Vacus J, Grossiord JL, Veillard M, et al. The design of nanoparticles obtained by solvent evaporation: a comprehensive study. Langmuir 2003;19:9504–10.
10. Zamani M, Prabhakaran MP, Ramakrishna S. Advances in drug delivery via electrospun and electrosprayed nanomaterials. Int J Nanomed 2013;8:2997–3017.
11. Abdel-Aziz A-AH, Asiri YA, El-Azab A, Al-Omar MA, Kunieda T. Tadalafil. Profiles Drug Subst Excipients Relat Methodol 2011;36:287–329.
12. Doggrell SA. Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. Expert Opin Pharmacother 2005;6:75–84.
13. Lu M, Xing H, Yang T, Yu J, Yang Z, Sun Y, et al. Dissolution enhancement of tadalafil by liquisolid technique. Pharm Dev Technol 2017;22:77–89.
14. Refaat A, Sokar M, Ismail F, Boraei N. Tadalafil oral disintegrating tablets: an approach to enhance tadalafil dissolution. J Pharm Investig 2015;45:481–91.
15. Badr-Eldin SM, Elkheshen SA, Ghorab MM. Inclusion complexes of tadalafil with natural and chemically modified???-cyclodextrins. I: preparation and in vitro evaluation. Eur J Pharm Biopharm 2008;70:819–27.
16. Obeidat WM, Sallam ASA. Evaluation of tadalafil nanosuspensions and their PEG solid dispersion matrices for enhancing its dissolution properties. AAPS PharmSciTech 2014;15:364–74.
17. Vinesha V, Sevukarajan M, Rajalakshmi R, Chowdary GT, Haritha K. Enhancement of solubility of tadalafil by cocrystal approach. Int Res J Pharm 2016;4:218–23.
18. Mehanna MM, Motawaa AM, Samaha MW. Tadalafil inclusion in microporous silica as an effective dissolution enhancer: optimization of loading procedure and molecular state characterization. J Pharm Sci 2011;100:1805–18.
19. Shen X, Yu D, Zhu L, Branford White C, White K, Chatterton NP. Electrospun diclofenac sodium loaded Eudragit?? L 100-55 nanofibers for colon-targeted drug delivery. Int J Pharm 2011;408:200–7.
20. Mehanna MM, Alwattar JK, Elmaradny HA. Optimization, physicochemical characterization and in vivo assessment of spray-dried emulsion: a step toward bioavailability augmentation and gastric toxicity minimization. Int J Pharm 2015;496:766–79.
21. Mehanna MM, Motawaa AM, Samaha MW. Insight into tadalafil-block copolymer binary solid dispersion: mechanistic investigation of dissolution enhancement. Int J Pharm 2010;402:78–88.
22. Sakuma S, Matsumoto S, Ishizuka N, Mohri K, Fukushima M, Ohba C, et al. Enhanced boosting of oral absorption of lopinavir through electrospray coencapsulation with ritonavir. J Pharm Sci 2015;104:2977–85.
23. Li C, Yu DG, Williams GR, Wang ZH. Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process. PLoS One 2014;9:1–9.
24. Yousaf AM, Mustapha O, Kim DW, Kim DS, Kim KS, Jin SG, et al. Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate. Int J Nanomed 2016;11:213–21.
25. Zhou Y, Qi P, Zhao Z, Liu Q, Li Z. Fabrication and characterization of fibrous HAP/PVP/PEO composites prepared by sol-electrospinning. RSC Adv 2014;4:16731.
26. Bhattarai N, Edmondson D, Veiseh O, Matsen FA, Zhang M. Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials 2005;26:6176–84.
27. Hong SI, Oh SY. Dissolution kinetics and physical characterization of the three-layered tablet with poly(ethylene oxide) core matrix capped by carbopol. Int J Pharm 2008;356:121–9.
28. Nasir M, Matsumoto H, Danno T, Minagawa M, Irisawa T, Shioya M, et al. Control of diameter, morphology, and structure of PVDF nanofiber fabricated by electrospray deposition. J Polymer Sci Part B: Polymer Physics 2006;44:779–86.
29. Huang L, Nagapudi K, Apkarian RP, Chaikof EL. Engineered collagen–PEO nano bers and fabrics. J Biomater Sci Polym Edn 2001;12:979–93.
30. Ajao JA, Abiona AA, Chigome S, Fasasi AY, Osinkolu GA, Maaza M. Electric-magnetic field-induced aligned electrospun poly (ethylene oxide) (PEO) nanofibers. J Mater Sci 2010;45:2324–9.
31. Yu DG, Branford White C, Shen XX, Zhang XF, Zhu LM. Solid dispersions of ketoprofen in drug-loaded electrospun nanofibers. J Dispers Sci Technol 2010;31:902–8.
32. Noor SAM, Ahmad A, Talib IA, Rahman MYA. Morphology, chemical interaction, and conductivity of a PEO-ENR50 based on solid polymer electrolyte. Ionics (Kiel) 2010;16:161–70.
2. Bohr A, Kristensen J, Dyas M, Edirisinghe M, Stride E. Release profile and characteristics of electrosprayed particles for oral delivery of a practically insoluble drug. J R Soc Interface 2012;9:2437–49.
3. Xie J, Marijnissen JCM, Wang CH. Microparticles developed by electrohydrodynamic atomization for the local delivery of an anticancer drug to treat C6 glioma in vitro. Biomaterials 2006;27:3321–32.
4. Zolkepali NK, Abu bakar NF, Naim MN, Anuar N, Kamalul Aripin NF, Abu Bakar MR, et al. Formation of fine and encapsulated mefenamic acid form I particles for dissolution improvement via electrospray method. Part Sci Technol 2018;36:298–307.
5. Vemula VR, Lagishetty V, Lingala S. Solubility enhancement techniques. Int J Pharm Sci Rev Res 2010;5:41–51.
6. Yu H, Teo J, Chew JW, Hadinoto K. Dry powder inhaler formulation of high-payload antibiotic nanoparticle complex intended for bronchiectasis therapy: spray drying versus spray freeze drying preparation. Int J Pharm 2016;499:38–46.
7. Das S, Banerjee R, Bellare J. Aspirin loaded albumin nanoparticles by coacervation: implications in drug delivery. Trends Biomater Artif Organs 2005;18:203–12.
8. Kwon HY, Lee JY, Choi SW, Jang Y, Kim JH. Preparation of PLGA nanoparticles containing estrogen by an emulsification-diffusion method. Colloids Surf A 2001;182:123–30.
9. Desgouilles S, Vauthier C, Bazile D, Vacus J, Grossiord JL, Veillard M, et al. The design of nanoparticles obtained by solvent evaporation: a comprehensive study. Langmuir 2003;19:9504–10.
10. Zamani M, Prabhakaran MP, Ramakrishna S. Advances in drug delivery via electrospun and electrosprayed nanomaterials. Int J Nanomed 2013;8:2997–3017.
11. Abdel-Aziz A-AH, Asiri YA, El-Azab A, Al-Omar MA, Kunieda T. Tadalafil. Profiles Drug Subst Excipients Relat Methodol 2011;36:287–329.
12. Doggrell SA. Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. Expert Opin Pharmacother 2005;6:75–84.
13. Lu M, Xing H, Yang T, Yu J, Yang Z, Sun Y, et al. Dissolution enhancement of tadalafil by liquisolid technique. Pharm Dev Technol 2017;22:77–89.
14. Refaat A, Sokar M, Ismail F, Boraei N. Tadalafil oral disintegrating tablets: an approach to enhance tadalafil dissolution. J Pharm Investig 2015;45:481–91.
15. Badr-Eldin SM, Elkheshen SA, Ghorab MM. Inclusion complexes of tadalafil with natural and chemically modified???-cyclodextrins. I: preparation and in vitro evaluation. Eur J Pharm Biopharm 2008;70:819–27.
16. Obeidat WM, Sallam ASA. Evaluation of tadalafil nanosuspensions and their PEG solid dispersion matrices for enhancing its dissolution properties. AAPS PharmSciTech 2014;15:364–74.
17. Vinesha V, Sevukarajan M, Rajalakshmi R, Chowdary GT, Haritha K. Enhancement of solubility of tadalafil by cocrystal approach. Int Res J Pharm 2016;4:218–23.
18. Mehanna MM, Motawaa AM, Samaha MW. Tadalafil inclusion in microporous silica as an effective dissolution enhancer: optimization of loading procedure and molecular state characterization. J Pharm Sci 2011;100:1805–18.
19. Shen X, Yu D, Zhu L, Branford White C, White K, Chatterton NP. Electrospun diclofenac sodium loaded Eudragit?? L 100-55 nanofibers for colon-targeted drug delivery. Int J Pharm 2011;408:200–7.
20. Mehanna MM, Alwattar JK, Elmaradny HA. Optimization, physicochemical characterization and in vivo assessment of spray-dried emulsion: a step toward bioavailability augmentation and gastric toxicity minimization. Int J Pharm 2015;496:766–79.
21. Mehanna MM, Motawaa AM, Samaha MW. Insight into tadalafil-block copolymer binary solid dispersion: mechanistic investigation of dissolution enhancement. Int J Pharm 2010;402:78–88.
22. Sakuma S, Matsumoto S, Ishizuka N, Mohri K, Fukushima M, Ohba C, et al. Enhanced boosting of oral absorption of lopinavir through electrospray coencapsulation with ritonavir. J Pharm Sci 2015;104:2977–85.
23. Li C, Yu DG, Williams GR, Wang ZH. Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process. PLoS One 2014;9:1–9.
24. Yousaf AM, Mustapha O, Kim DW, Kim DS, Kim KS, Jin SG, et al. Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate. Int J Nanomed 2016;11:213–21.
25. Zhou Y, Qi P, Zhao Z, Liu Q, Li Z. Fabrication and characterization of fibrous HAP/PVP/PEO composites prepared by sol-electrospinning. RSC Adv 2014;4:16731.
26. Bhattarai N, Edmondson D, Veiseh O, Matsen FA, Zhang M. Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials 2005;26:6176–84.
27. Hong SI, Oh SY. Dissolution kinetics and physical characterization of the three-layered tablet with poly(ethylene oxide) core matrix capped by carbopol. Int J Pharm 2008;356:121–9.
28. Nasir M, Matsumoto H, Danno T, Minagawa M, Irisawa T, Shioya M, et al. Control of diameter, morphology, and structure of PVDF nanofiber fabricated by electrospray deposition. J Polymer Sci Part B: Polymer Physics 2006;44:779–86.
29. Huang L, Nagapudi K, Apkarian RP, Chaikof EL. Engineered collagen–PEO nano bers and fabrics. J Biomater Sci Polym Edn 2001;12:979–93.
30. Ajao JA, Abiona AA, Chigome S, Fasasi AY, Osinkolu GA, Maaza M. Electric-magnetic field-induced aligned electrospun poly (ethylene oxide) (PEO) nanofibers. J Mater Sci 2010;45:2324–9.
31. Yu DG, Branford White C, Shen XX, Zhang XF, Zhu LM. Solid dispersions of ketoprofen in drug-loaded electrospun nanofibers. J Dispers Sci Technol 2010;31:902–8.
32. Noor SAM, Ahmad A, Talib IA, Rahman MYA. Morphology, chemical interaction, and conductivity of a PEO-ENR50 based on solid polymer electrolyte. Ionics (Kiel) 2010;16:161–70.
Published
15-01-2020
How to Cite
MEHANNA, M. M., and J. K. ALWATTAR. “NANOSPHERE-LOADED TADALAFIL WITH ENHANCED ORAL BIOAVAILABILITY: INNOVATIVE APPLICATION OF ELECTROHYDRODYNAMIC TECHNIQUE”. International Journal of Current Pharmaceutical Research, vol. 12, no. 1, Jan. 2020, pp. 28-34, doi:10.22159/ijcpr.2020v12i1.36828.
Issue
Section
Original Article(s)
