Araştırma Makalesi
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TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ

Yıl 2021, , 264 - 283, 31.05.2021
https://doi.org/10.33483/jfpau.811737

Öz

Amaç: Suda çözünürlüğü bulunmayan iyot bazlı triiyodoanilin (TIA) radyokontrast bileşiğinin sentezini ve nanosüspansiyonunu yapmak, karakterizasyonlarını gerçekleştirmek ve Bilgisayarlı Tomografi (BT) görüntülemede sıklıkla kullanılan iopromid ve ioheksol ile kıyaslamak.
Gereç ve Yöntem: TIA sentezi ultrasonik ses dalgaları kullanılarak ve nanokristaller ise sentezlenen bu maddeden hareketle nanopresipitasyon yöntemi ile elde edilmiştir. TIA’nın karakterizasyonu için NMR ve Q-TOF analizleri yapılmıştır. Nanokristallerin karakterizasyonu için ise optik mikroskop, zeta potansiyel, partikül boyutu ve dağılımı, SEM ve FT-IR analizleri yapılmıştır. Elde edilen nanosüspansiyon, BT tekniği ile iopromid ve ioheksol.ile radyokontrast özellikleri açısından kıyaslanmıştır.
Sonuç ve Tartışma: Sentezlenen saf TIA’dan hareketle hazırlanan nanokristallerin boyutları ~699 nm, zeta potansiyelleri ise ~(-)16 mV olarak bulunmuştur. SEM ve optik mikroskop görüntüleri ile morfolojileri belirlenmiştir. Elde edilen nanokristallerin, sentezlenen TIA’dan farklı bir yapı sergilemediği FT-IR ile tespit edilmiştir. BT görüntülerinde TIA nanosüspansiyonunun, aynı miktardaki iopromid ve ioheksolden yaklaşık ~%40 daha fazla kontrast özellik sergilediği tespit edilmiştir. Sonuç olarak nanokristallerin kendi sahip oldukları eşsiz özellikleri ile daha az radyokontrast madde kullanılarak benzer nitelikte görüntüleme yapılabileceği gösterilmiştir. Bu sayede daha düşük dozda kullanım sunması sebebiyle daha az yan etki ve/veya toksik etki oluşturması muhtemeldir. Elde edilen bu başarılı sonuçlar ışığında, klinik deneyler ile bu çalışmanın gelecekte detaylandırılması planlanmaktadır.

Teşekkür

BT görüntülerinin alınmasında desteğini esirgemeyen Atatürk Üniversitesi Tıp Fakültesi Radyoloji Anabilim Dalından Doç. Dr. Recep SADE’ye teşekkürlerimizi sunarız.

Kaynakça

  • 1. Caschera, L., Lazzara, A., Piergallini, L., Ricci, D., Tuscano, B., Vanzulli, A. (2016). Contrast agents in diagnostic imaging: Present and future. Pharmacological Research, 110, 65-75.
  • 2. Koc, M.M., Aslan, N., Kao, A.P., Barber, A.H. (2019). Evaluation of X-ray tomography contrast agents: A review of production, protocols, and biological applications. Microscopy Research and Technique, 82(6), 812-848.
  • 3. Almen, T. (1985). Development of nonionic contrast-media. Investigative Radiology, 20(1), 2-9.
  • 4. Müller, R.H., Gohla, S., Keck, C.M. (2011). State of the art of nanocrystals – Special features, production,nanotoxicology aspects and intracellular delivery. European Journal of Pharmaceutics and Biopharmaceutics, 78, 1-9.
  • 5. Wang, Y., Zheng, Y., Zhang, L., Wang, Q., Zhang, D. (2013). Stability of nanosuspensions in drug delivery. Journal of Controlled Release, 172, 1126-1141.
  • 6. Gao, L., Liu, G., Ma, J., Wang, X., Zhou, L., Li, X. (2012). Drug nanocrystals:In vivo performances. Journal of Controlled Release, 160, 418-430.
  • 7. Wang, L.L., Du, J., Zhou, Y.Q., Wang, Y.C. (2017). Safety of nanosuspensions in drug delivery. Nanomedicine: Nanotechnology, Biology, and Medicine, 13(2), 455-469.
  • 8. Kamaly, N., He, J.C., Ausiello, D.A., Farokhzad, O.C. (2016). Nanomedicines for renal disease: current status and future applications. Nature Reviews Nephrology, 12(12), 738-753.
  • 9. Khan, I., Saeed, K., Khan, I. (2019). Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry, 12(7), 908-931.
  • 10. Williams, R.M., Jaimes, E.A., Heller, D.A. (2016). Nanomedicines for kidney diseases. Kidney International, 90(4), 740-745.
  • 11. Thurman, J.M., Serkova, N.J. (2013). Nanosized contrast agents to noninvasively detect kidney inflammation by magnetic resonance imaging. Advances in Chronic Kidney Disease, 20(6), 488-499. 12. Debbage, P., Jaschke, W. (2008). Molecular imaging with nanoparticles: Giant roles for dwarf actors. Histochemistry and Cell Biology, 130(5), 845-875.
  • 13. Chemical Book Web site. (2017). Retrieved September 28, from https://www.chemicalbook.com/ChemicalProductProperty_EN_cb5125267.htm.
  • 14. Chemical Book Web site. (2017). Retrieved September 29, from https://www.chemicalbook.com/ChemicalProductProperty_EN_cb5110557.htm.
  • 15. ChemSpider Web site. (2020). Retrieved September 29, from http://www.chemspider.com/Chemical-Structure.193223.html.
  • 16. Sahu, B.P., Das, M.K. (2014). Nanosuspension for enhancement of oral bioavailability of felodipine. Applied Nanoscience, 4(2), 189-197.
  • 17. Ferreira, I.M., Casagrande, G.A., Pizzuti, L., Raminelli, C. (2014). Ultrasound-promoted rapid and efficient iodination of aromatic and heteroaromatic compounds in the presence of iodine and hydrogen peroxide in water. Synthetic Communications, 44(14), 2094-2102.
  • 18. Rao, J.P., Geckeler, K.E. (2011). Polymer nanoparticles: Preparation techniques and size-control parameters. Progress in Polymer Science, 36(7), 887-913.
  • 19. Pirimoglu, B., Sade, R., Sakat, M.S., Ogul, H., Levent, A., Kantarci, M. (2018). Low-dose noncontrast examination of the paranasal sinuses using volumetric computed tomography. Journal of Computer Assisted Tomography, 42(3), 482-486.
  • 20. Pirimoglu, B., Sade, R., Sakat, M.S., Polat, G., Kantarci, M. (2019). Low-dose non-contrast examination of the temporal bone using volumetric 320-row computed tomography. Acta Radiologica, 60(7), 908-916.
  • 21. Ravichandran, R. (2009). Nanoparticles in drug delivery: Potential green nanobiomedicine applications. International Journal of Green Nanotechnology: Biomedicine, 1(2), 108-130.
  • 22. De Simone, B., Ansaloni, L., Sartelli, M., Gaiani, F., Leandro, G., De' Angelis, G.L., Di Mario, F., Coccolini, F., Catena, F. (2018). Is the risk of contrast-induced nephropathy a real contraindication to perform intravenous contrast enhanced Computed Tomography for non-traumatic acute abdomen in Emergency Surgery Department?. Acta Biomedica, 89(9-S), 158-172.
  • 23. Mohammed, N.M.A., Mahfouz, A., Achkar, K., Rafie, I.M., Hajar, R. (2013). Contrast-induced nephropathy. Heart Views : The Official Journal of the Gulf Heart Association, 14(3), 106-116.
  • 24. Cosmai, L., Porta, C., Privitera, C., Gesualdo, L., Procopio, G., Gori, S., et al. (2020). Acute kidney injury from contrast-enhanced CT procedures in patients with cancer: White paper to highlight its clinical relevance and discuss applicable preventive strategies. ESMO Open, 5(2), 1-8.
  • 25. Sovak, M., Ranganathan, R. (1980). Stability of nonionic water-soluble contrast media: implications for their design. Investigative Radiology, 15(6), S323-328.
  • 26. The LibreTexts Web site. (2006). Retrieved January 05, 2021, from https://chem.libretexts.org/Bookshelves/General_Chemistry/Map%3A_Chemistry_-_The_Central_Science_(Brown_et_al.)/13%3A_Properties_of_Solutions
  • 27. Cormode, D.P., Naha, P.C., Fayad, Z.A. (2014). Nanoparticle contrast agents for computed tomography: a focus on micelles. Contrast Media & Molecular Imaging, 9(1), 37-52.
  • 28. Ashton, J.R., West, J.L., Badea, C.T. (2015). In vivo small animal micro-CT using nanoparticle contrast agents. Frontiers in Pharmacology, 6, 1-22.
  • 29. Williams, R.M., Shah, J., Tian, H.S., Chen, X., Geissmann, F., Jaimes, E.A., Heller, D.A. (2018). Selective nanoparticle targeting of the renal tubules. Hypertension, 71(1), 87-94.
  • 30. Han, X.J., Xu, K., Taratula, O., Farsad, K. (2019). Applications of nanoparticles in biomedical imaging. Nanoscale, 11(3), 799-819.
  • 31. Hainfeld, J.F., Ridwan, S.M., Stanishevskiy, Y., Smilowitz, N.R., Davis, J., Smilowitz, H.M. (2018). Small, long blood half-life iodine nanoparticle for vascular and tumor imaging. Scientific Reports, 8, 1-10.
  • 32. Kim, J., Lee, N., Hyeon, T. (2017). Recent development of nanoparticles for molecular imaging. Philosophical Transactions of the Royal Society A, 375(2107), 1-17.
  • 33. Patel, V.R., Agrawal, Y. (2011). Nanosuspension: An approach to enhance solubility of drugs. Journal of Advanced Pharmaceutical Technology & Research, 2(2), 81-87.
  • 34. Sutradhar, K.B., Khatun, S., Luna, I.P. (2013). Increasing possibilities of nanosuspension. Journal of Nanotechnology, 2013, 1-12.
  • 35. Rabinow, B., Kipp, J., Papadopoulos, P., Wong, J., Glosson, J., Gass, J., et al. (2007). Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. International Journal of Pharmaceutics, 339(1-2), 251-260.
  • 36. Merisko-Liversidge, E., Liversidge, G.G., Cooper, E.R. (2003). Nanosizing: A formulation approach for poorly-water-soluble compounds. European Journal of Pharmaceutical Sciences, 18(2), 113-120.
  • 37. Peters, K., Leitzke, S., Diederichs, J.E., Borner, K., Hahn, H., Müller, R.H., Ehlers, S. (2000). Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. Journal of Antimicrobial Chemotherapy, 45(1), 77-83.
  • 38. Kalvakuntla, S., Deshpande, M., Attari, Z., Kunnatur, K. (2016). Preparation and characterization of nanosuspension of aprepitant by H96 process. Advanced Pharmaceutical Bulletin, 6(1), 83-90.
  • 39. Singare, D.S., Marella, S., Gowthamrajan, K., Kulkarni, G.T., Vooturi, R., Rao, P.S. (2010). Optimization of formulation and process variable of nanosuspension: An industrial perspective. International Journal of Pharmaceutics, 402(1-2), 213-220.
  • 40. Singh, S., Singh, S.K., Chauhan, M.G., Kumar, B., Pandey, N.K., Kaur, B., Kumar, A., Mohanta, S., Gulati, M., Wadhwa, S., Yadav, A.K., Singh, P.K., Kumari, Y., Kaur, G., Khursheed, R., Clarisse, A. (2019). Quality by design-based optimization of formulation and process variables for controlling particle size and zeta potential of spray dried incinerated copper nanosuspension. Recent Innovations in Chemical Engineering, 12(3), 248-260.
  • 41. Karakucuk, A., Celebi, N. (2020). Investigation of formulation and process parameters of wet media milling to develop etodolac nanosuspensions. Pharmaceutical Research, 37, 1-18.
  • 42. Ali, H.S., York, P., Blagden, N. (2009). Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors. International Journal of Pharmaceutics, 375(1-2), 107-113.
  • 43. Patravale, V.B., Date, A.A., Kulkarni, R.M. (2004). Nanosuspensions: A promising drug delivery strategy. Journal of Pharmacy and Pharmacology, 56, 827-840.
  • 44. Moorthi, C., Krishnan, K., Manavalan, R., Kathiresan, K. (2012). Preparation and characterization of curcumin–piperine dual drug loaded nanoparticles. Asian Pacific Journal of Tropical Biomedicine, 2(11), 841-848.
  • 45. Afifi, S.A., Hassan, M.A., Abdelhameed, A.S., Elkhodairy, K.A. (2015). Nanosuspension: An emerging trend for bioavailability enhancement of etodolac. International Journal of Polymer Science, 2015, 1-16.
  • 46. Wiśniewska, M., Ostolska, I., Szewczuk-Karpisz, K., Chibowski, S., Terpiłowski, K., Gun’ko, V.M., Zarko, V.I. (2015). Investigation of the polyvinyl alcohol stabilization mechanism and adsorption properties on the surface of ternary mixed nanooxide AST 50 (Al2O3–SiO2–TiO2). Journal of Nanoparticle Research, 17(12), 1-14.
  • 47. Abdelbary, A.A., Li, X., El-Nabarawi, M., Elassasy, A., Jasti, B. (2013). Effect of fixed aqueous layer thickness of polymeric stabilizers on zeta potential and stability of aripiprazole nanosuspensions. Pharmaceutical Development and Technology, 18(3), 730-735.
  • 48. Müller, R., Jacobs, C. (2002). Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability. International Journal of Pharmaceutics, 237(1-2), 151-161.

SYNTHESIS OF TRIIODOANILINE, PREPARATION OF NANOSUSPENSIONS, IN VITRO CHARACTERIZATION AND INVESTIGATION OF RADIOCONTRAST PROPERTIES

Yıl 2021, , 264 - 283, 31.05.2021
https://doi.org/10.33483/jfpau.811737

Öz

Objective: Synthesis and nanosuspension preparation of iodine-based triiodoaniline (TIA) radiocontrast compound, which is not soluble in water, perform their characterization and compare with iopromide and iohexol, which are frequently used in Computed Tomography (CT) imaging.
Material and Method: TIA synthesis was obtained using ultrasonic sound waves, and nanocrystals were obtained by nanoprecipitation method from this synthesized substance. NMR and Q-TOF analyzes were performed for the characterization of TIA. For the characterization of nanocrystals, optical microscope, zeta potential, particle size, and distribution, SEM and FT-IR analyzes were performed. The obtained nanosuspension was compared by the CT technique with iopromide and iohexol in terms of radiocontrast properties.
Result and Discussion: The size of the prepared nanoparticles based on the synthesized pure TIA was found to be ~699 nm and zeta potentials as ~ (-)16 mW. Morphologies were determined by SEM and optical microscope images. It was determined by FT-IR that the obtained nanocrystals do not exhibit a different structure than the synthesized TIA. On CT images, TIA nanosuspension was found to exhibit ~ 40% more contrast than the same amount of iopromide and iohexol. As a result, it has been shown that nanocrystals can perform similar imaging by using less radiocontrast materials with their unique properties. In this way, it is likely to cause fewer side effects and/or toxic effects due to the lower dosage. In the light of these successful results, it is planned to detail this study with clinical trials in the future.

Kaynakça

  • 1. Caschera, L., Lazzara, A., Piergallini, L., Ricci, D., Tuscano, B., Vanzulli, A. (2016). Contrast agents in diagnostic imaging: Present and future. Pharmacological Research, 110, 65-75.
  • 2. Koc, M.M., Aslan, N., Kao, A.P., Barber, A.H. (2019). Evaluation of X-ray tomography contrast agents: A review of production, protocols, and biological applications. Microscopy Research and Technique, 82(6), 812-848.
  • 3. Almen, T. (1985). Development of nonionic contrast-media. Investigative Radiology, 20(1), 2-9.
  • 4. Müller, R.H., Gohla, S., Keck, C.M. (2011). State of the art of nanocrystals – Special features, production,nanotoxicology aspects and intracellular delivery. European Journal of Pharmaceutics and Biopharmaceutics, 78, 1-9.
  • 5. Wang, Y., Zheng, Y., Zhang, L., Wang, Q., Zhang, D. (2013). Stability of nanosuspensions in drug delivery. Journal of Controlled Release, 172, 1126-1141.
  • 6. Gao, L., Liu, G., Ma, J., Wang, X., Zhou, L., Li, X. (2012). Drug nanocrystals:In vivo performances. Journal of Controlled Release, 160, 418-430.
  • 7. Wang, L.L., Du, J., Zhou, Y.Q., Wang, Y.C. (2017). Safety of nanosuspensions in drug delivery. Nanomedicine: Nanotechnology, Biology, and Medicine, 13(2), 455-469.
  • 8. Kamaly, N., He, J.C., Ausiello, D.A., Farokhzad, O.C. (2016). Nanomedicines for renal disease: current status and future applications. Nature Reviews Nephrology, 12(12), 738-753.
  • 9. Khan, I., Saeed, K., Khan, I. (2019). Nanoparticles: Properties, applications and toxicities. Arabian Journal of Chemistry, 12(7), 908-931.
  • 10. Williams, R.M., Jaimes, E.A., Heller, D.A. (2016). Nanomedicines for kidney diseases. Kidney International, 90(4), 740-745.
  • 11. Thurman, J.M., Serkova, N.J. (2013). Nanosized contrast agents to noninvasively detect kidney inflammation by magnetic resonance imaging. Advances in Chronic Kidney Disease, 20(6), 488-499. 12. Debbage, P., Jaschke, W. (2008). Molecular imaging with nanoparticles: Giant roles for dwarf actors. Histochemistry and Cell Biology, 130(5), 845-875.
  • 13. Chemical Book Web site. (2017). Retrieved September 28, from https://www.chemicalbook.com/ChemicalProductProperty_EN_cb5125267.htm.
  • 14. Chemical Book Web site. (2017). Retrieved September 29, from https://www.chemicalbook.com/ChemicalProductProperty_EN_cb5110557.htm.
  • 15. ChemSpider Web site. (2020). Retrieved September 29, from http://www.chemspider.com/Chemical-Structure.193223.html.
  • 16. Sahu, B.P., Das, M.K. (2014). Nanosuspension for enhancement of oral bioavailability of felodipine. Applied Nanoscience, 4(2), 189-197.
  • 17. Ferreira, I.M., Casagrande, G.A., Pizzuti, L., Raminelli, C. (2014). Ultrasound-promoted rapid and efficient iodination of aromatic and heteroaromatic compounds in the presence of iodine and hydrogen peroxide in water. Synthetic Communications, 44(14), 2094-2102.
  • 18. Rao, J.P., Geckeler, K.E. (2011). Polymer nanoparticles: Preparation techniques and size-control parameters. Progress in Polymer Science, 36(7), 887-913.
  • 19. Pirimoglu, B., Sade, R., Sakat, M.S., Ogul, H., Levent, A., Kantarci, M. (2018). Low-dose noncontrast examination of the paranasal sinuses using volumetric computed tomography. Journal of Computer Assisted Tomography, 42(3), 482-486.
  • 20. Pirimoglu, B., Sade, R., Sakat, M.S., Polat, G., Kantarci, M. (2019). Low-dose non-contrast examination of the temporal bone using volumetric 320-row computed tomography. Acta Radiologica, 60(7), 908-916.
  • 21. Ravichandran, R. (2009). Nanoparticles in drug delivery: Potential green nanobiomedicine applications. International Journal of Green Nanotechnology: Biomedicine, 1(2), 108-130.
  • 22. De Simone, B., Ansaloni, L., Sartelli, M., Gaiani, F., Leandro, G., De' Angelis, G.L., Di Mario, F., Coccolini, F., Catena, F. (2018). Is the risk of contrast-induced nephropathy a real contraindication to perform intravenous contrast enhanced Computed Tomography for non-traumatic acute abdomen in Emergency Surgery Department?. Acta Biomedica, 89(9-S), 158-172.
  • 23. Mohammed, N.M.A., Mahfouz, A., Achkar, K., Rafie, I.M., Hajar, R. (2013). Contrast-induced nephropathy. Heart Views : The Official Journal of the Gulf Heart Association, 14(3), 106-116.
  • 24. Cosmai, L., Porta, C., Privitera, C., Gesualdo, L., Procopio, G., Gori, S., et al. (2020). Acute kidney injury from contrast-enhanced CT procedures in patients with cancer: White paper to highlight its clinical relevance and discuss applicable preventive strategies. ESMO Open, 5(2), 1-8.
  • 25. Sovak, M., Ranganathan, R. (1980). Stability of nonionic water-soluble contrast media: implications for their design. Investigative Radiology, 15(6), S323-328.
  • 26. The LibreTexts Web site. (2006). Retrieved January 05, 2021, from https://chem.libretexts.org/Bookshelves/General_Chemistry/Map%3A_Chemistry_-_The_Central_Science_(Brown_et_al.)/13%3A_Properties_of_Solutions
  • 27. Cormode, D.P., Naha, P.C., Fayad, Z.A. (2014). Nanoparticle contrast agents for computed tomography: a focus on micelles. Contrast Media & Molecular Imaging, 9(1), 37-52.
  • 28. Ashton, J.R., West, J.L., Badea, C.T. (2015). In vivo small animal micro-CT using nanoparticle contrast agents. Frontiers in Pharmacology, 6, 1-22.
  • 29. Williams, R.M., Shah, J., Tian, H.S., Chen, X., Geissmann, F., Jaimes, E.A., Heller, D.A. (2018). Selective nanoparticle targeting of the renal tubules. Hypertension, 71(1), 87-94.
  • 30. Han, X.J., Xu, K., Taratula, O., Farsad, K. (2019). Applications of nanoparticles in biomedical imaging. Nanoscale, 11(3), 799-819.
  • 31. Hainfeld, J.F., Ridwan, S.M., Stanishevskiy, Y., Smilowitz, N.R., Davis, J., Smilowitz, H.M. (2018). Small, long blood half-life iodine nanoparticle for vascular and tumor imaging. Scientific Reports, 8, 1-10.
  • 32. Kim, J., Lee, N., Hyeon, T. (2017). Recent development of nanoparticles for molecular imaging. Philosophical Transactions of the Royal Society A, 375(2107), 1-17.
  • 33. Patel, V.R., Agrawal, Y. (2011). Nanosuspension: An approach to enhance solubility of drugs. Journal of Advanced Pharmaceutical Technology & Research, 2(2), 81-87.
  • 34. Sutradhar, K.B., Khatun, S., Luna, I.P. (2013). Increasing possibilities of nanosuspension. Journal of Nanotechnology, 2013, 1-12.
  • 35. Rabinow, B., Kipp, J., Papadopoulos, P., Wong, J., Glosson, J., Gass, J., et al. (2007). Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. International Journal of Pharmaceutics, 339(1-2), 251-260.
  • 36. Merisko-Liversidge, E., Liversidge, G.G., Cooper, E.R. (2003). Nanosizing: A formulation approach for poorly-water-soluble compounds. European Journal of Pharmaceutical Sciences, 18(2), 113-120.
  • 37. Peters, K., Leitzke, S., Diederichs, J.E., Borner, K., Hahn, H., Müller, R.H., Ehlers, S. (2000). Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. Journal of Antimicrobial Chemotherapy, 45(1), 77-83.
  • 38. Kalvakuntla, S., Deshpande, M., Attari, Z., Kunnatur, K. (2016). Preparation and characterization of nanosuspension of aprepitant by H96 process. Advanced Pharmaceutical Bulletin, 6(1), 83-90.
  • 39. Singare, D.S., Marella, S., Gowthamrajan, K., Kulkarni, G.T., Vooturi, R., Rao, P.S. (2010). Optimization of formulation and process variable of nanosuspension: An industrial perspective. International Journal of Pharmaceutics, 402(1-2), 213-220.
  • 40. Singh, S., Singh, S.K., Chauhan, M.G., Kumar, B., Pandey, N.K., Kaur, B., Kumar, A., Mohanta, S., Gulati, M., Wadhwa, S., Yadav, A.K., Singh, P.K., Kumari, Y., Kaur, G., Khursheed, R., Clarisse, A. (2019). Quality by design-based optimization of formulation and process variables for controlling particle size and zeta potential of spray dried incinerated copper nanosuspension. Recent Innovations in Chemical Engineering, 12(3), 248-260.
  • 41. Karakucuk, A., Celebi, N. (2020). Investigation of formulation and process parameters of wet media milling to develop etodolac nanosuspensions. Pharmaceutical Research, 37, 1-18.
  • 42. Ali, H.S., York, P., Blagden, N. (2009). Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors. International Journal of Pharmaceutics, 375(1-2), 107-113.
  • 43. Patravale, V.B., Date, A.A., Kulkarni, R.M. (2004). Nanosuspensions: A promising drug delivery strategy. Journal of Pharmacy and Pharmacology, 56, 827-840.
  • 44. Moorthi, C., Krishnan, K., Manavalan, R., Kathiresan, K. (2012). Preparation and characterization of curcumin–piperine dual drug loaded nanoparticles. Asian Pacific Journal of Tropical Biomedicine, 2(11), 841-848.
  • 45. Afifi, S.A., Hassan, M.A., Abdelhameed, A.S., Elkhodairy, K.A. (2015). Nanosuspension: An emerging trend for bioavailability enhancement of etodolac. International Journal of Polymer Science, 2015, 1-16.
  • 46. Wiśniewska, M., Ostolska, I., Szewczuk-Karpisz, K., Chibowski, S., Terpiłowski, K., Gun’ko, V.M., Zarko, V.I. (2015). Investigation of the polyvinyl alcohol stabilization mechanism and adsorption properties on the surface of ternary mixed nanooxide AST 50 (Al2O3–SiO2–TiO2). Journal of Nanoparticle Research, 17(12), 1-14.
  • 47. Abdelbary, A.A., Li, X., El-Nabarawi, M., Elassasy, A., Jasti, B. (2013). Effect of fixed aqueous layer thickness of polymeric stabilizers on zeta potential and stability of aripiprazole nanosuspensions. Pharmaceutical Development and Technology, 18(3), 730-735.
  • 48. Müller, R., Jacobs, C. (2002). Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability. International Journal of Pharmaceutics, 237(1-2), 151-161.
Toplam 47 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Eczacılık ve İlaç Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Mehmet Koca Bu kişi benim 0000-0002-1517-5925

Emrah Özakar 0000-0002-7443-208X

Rukiye Sevinç Özakar 0000-0002-2972-8084

Yayımlanma Tarihi 31 Mayıs 2021
Gönderilme Tarihi 16 Ekim 2020
Kabul Tarihi 30 Mart 2021
Yayımlandığı Sayı Yıl 2021

Kaynak Göster

APA Koca, M., Özakar, E., & Sevinç Özakar, R. (2021). TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ. Journal of Faculty of Pharmacy of Ankara University, 45(2), 264-283. https://doi.org/10.33483/jfpau.811737
AMA Koca M, Özakar E, Sevinç Özakar R. TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ. Ankara Ecz. Fak. Derg. Mayıs 2021;45(2):264-283. doi:10.33483/jfpau.811737
Chicago Koca, Mehmet, Emrah Özakar, ve Rukiye Sevinç Özakar. “TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ”. Journal of Faculty of Pharmacy of Ankara University 45, sy. 2 (Mayıs 2021): 264-83. https://doi.org/10.33483/jfpau.811737.
EndNote Koca M, Özakar E, Sevinç Özakar R (01 Mayıs 2021) TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ. Journal of Faculty of Pharmacy of Ankara University 45 2 264–283.
IEEE M. Koca, E. Özakar, ve R. Sevinç Özakar, “TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ”, Ankara Ecz. Fak. Derg., c. 45, sy. 2, ss. 264–283, 2021, doi: 10.33483/jfpau.811737.
ISNAD Koca, Mehmet vd. “TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ”. Journal of Faculty of Pharmacy of Ankara University 45/2 (Mayıs 2021), 264-283. https://doi.org/10.33483/jfpau.811737.
JAMA Koca M, Özakar E, Sevinç Özakar R. TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ. Ankara Ecz. Fak. Derg. 2021;45:264–283.
MLA Koca, Mehmet vd. “TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ”. Journal of Faculty of Pharmacy of Ankara University, c. 45, sy. 2, 2021, ss. 264-83, doi:10.33483/jfpau.811737.
Vancouver Koca M, Özakar E, Sevinç Özakar R. TRİİYODOANİLİN’İN SENTEZLENMESİ, NANOSÜSPANSİYONLARININ HAZIRLANMASI, İN VİTRO KARAKTERİZASYONU VE RADYOKONTRAST ÖZELLİKLERİNİN İNCELENMESİ. Ankara Ecz. Fak. Derg. 2021;45(2):264-83.

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.