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DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES

Yıl 2023, Cilt: 47 Sayı: 2, 324 - 335, 20.05.2023

Gizem Rüya Topal Cansel Köse Özkan Yalçın Özkan

https://doi.org/10.33483/jfpau.1194470

Öz

Objective: In this study, it was aimed to prepare nanosuspensions that contains Indomethacin which is a BCS class II drug. To assess the cumulative impact of the chosen variables on the nanosuspension properties, a 34 factorial design was applied and particle size and distributions were examined.
Material and Method: In the study, the solvent/antisolvent method was used in the preparation of the suspensions. 34 factorial design. Design-Expert software was used for the evaluation of the prepared formulations in order to obtain the best formulation. PVA concentration, PVA molecular weight, solvent/antisolvent ratio, and ethanol/PEG 300 ratio were used as independent design parameters, and their effects on particle size and distribution were examined.
Result and Discussion: Nanosuspensions were successfully prepared by the solvent/antisolvent method. Particle size and polydispersity index of the nanosuspensions were found to be affected by both molecular weight and percentage of PVA in the antisolvent phase (p ˂ 0.05). 0.2% (w/v) PVA; molecular weight of 31 000 for PVA and the solvent-antisolvent ratio as 3:50 were found to be the optimal parameters for the nanosuspension formulations. The particle size and polydispersity of optimum formulation were found 301.5 ± 31.1 nm and 0.159 ± 0.035, respectively.

Anahtar Kelimeler

Factorial design Solvent/antisolvent method Indomethacin Nanosuspension

Kaynakça

  • 1. Ahmadi Tehrani, A., Omranpoor, M.M., Vatanara, A., Seyedabadi, M., Ramezani, V. (2019). Formation of nanosuspensions in bottom-up approach: theories and optimization. DARU Journal of Pharmaceutical Sciences, 27(1), 451-473. [CrossRef]
  • 2. Ghosh, I., Schenck, D., Bose, S., Liu, F., Motto, M. (2013). Identification of critical process parameters and its interplay with nanosuspension formulation prepared by top down media milling technology-a QbD perspective. Pharmaceutical Development & Technology, 18(3), 719-729. [CrossRef]
  • 3. Ghosh, I., Schenck, D., Bose, S., Ruegger, C. (2012). Optimization of formulation and process parameters for the production of nanosuspension by wet media milling technique: effect of Vitamin E TPGS and nanocrystal particle size on oral absorption. European Journal of Pharmaceutical Sciences, 47(4), 718-728. [CrossRef]
  • 4. Patravale, V.B., Date, A.A., Kulkarni, R.M. (2004). Nanosuspensions: A promising drug delivery strategy. Journal of Pharmacy and Pharmacology, 56(7), 827-840. [CrossRef]
  • 5. Verma, S., Lan, Y., Gokhale, R., Burgess, D.J. (2009). Quality by design approach to understand the process of nanosuspension preparation. International Journal of Pharmaceutics, 377(1-2), 185-198. [CrossRef]
  • 6. Patel, V.R., Agrawal, Y.K. (2011). Nanosuspension: An approach to enhance solubility of drugs. Journal of Advanced Pharmaceutical Technology & Research, 2(2), 81-87. [CrossRef]
  • 7. Mahesh, K.V., Singh, S.C., Gulati, M. (2014). A comparative study of top-down and bottom-up approaches for the preparation of nanosuspensions of glipizide. Powder Technology, 256, 436-449. [CrossRef]
  • 8. Esim, O., Bakirhan, N.K., Yildirim, N., Sarper, M., Savaser, A., Ozkan, S.A., Ozkan, Y. (2020). Development, optimization and in vitro evaluation of oxaliplatin loaded nanoparticles in non-small cell lung cancer. DARU Journal of Pharmaceutical Sciences, 28(2), 673-684. [CrossRef]
  • 9. Gajera, B.Y., Shah, D.A., Dave, R.H. (2019). Development of an amorphous nanosuspension by sonoprecipitation-formulation and process optimization using design of experiment methodology. International Journal of Pharmaceutics, 559, 348-359. [CrossRef]
  • 10. 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), 213-220. [CrossRef]
  • 11. Shariare, M.H., Sharmin, S., Jahan, I., Reza, H.M., Mohsin, K. (2018). The impact of process parameters on carrier free paracetamol nanosuspension prepared using different stabilizers by antisolvent precipitation method. Journal of Drug Delivery Science and Technology, 43,122-1228. [CrossRef]
  • 12. Shariare, M.H., Altamimi, M.A., Marzan, A.L., Tabassum, R., Jahan, B., Reza, H.M., Rahman, M., Ahsan, G.U., Kazi, M. (2019). In vitro dissolution and bioavailability study of furosemide nanosuspension prepared using design of experiment (DoE). Saudi Pharmaceutical Journal, 27(1), 96-105. [CrossRef]
  • 13. Mishra, B., Sahoo, J., Dixit, P.K. (2016). Enhanced bioavailability of cinnarizine nanosuspensions by particle size engineering: Optimization and physicochemical investigations. Materials Science and Engineering: C, 63, 62-69. [CrossRef]
  • 14. Karakucuk, A., Celebi, N. (2020). Investigation of formulation and process parameters of wet media milling to develop etodolac nanosuspensions. Pharmaceutical Research, 37(6), 111. [CrossRef]
  • 15. Bolton, S., Bor, S. (2003). Pharmaceutical Statistics: Practical and Clinical Applications, Revised and Expanded, CRC Press.
  • 16. Anwer, M.K., Al-Mansoor, M.A., Jamil, S., Al-Shdefat, R., Ansari, M.N., Shakeel, F. (2016). Development and evaluation of PLGA polymer based nanoparticles of quercetin. International Journal of Biological Macromolecules, 92, 213-219. [CrossRef]
  • 17. Patil, A.S., Hegde, R., Gadad, A.P., Dandagi, P.M., Masareddy, R., Bolmal, U. (2021). Exploring the solvent-anti-solvent method of nanosuspension for enhanced oral bioavailability of lovastatin. Turkish Journal of Pharmaceutical Sciences, 18(5), 541-549. [CrossRef]
  • 18. Kuk, D.H., Ha, E.S., Ha, D.H., Sim, W.Y., Lee, S.K., Jeong, J.S., Kim, J.S., Baek, I.H., Park, H., Choi, D.H., Yoo, J.W., Jeong, S.H., Hwang, S.J., Kim, M.S. (2019). Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach. Pharmaceutics, 11(12), 688. [CrossRef]
  • 19. Esim, O., Savaser, A., Ozkan, C.K., Bayrak, Z., Tas, C., Ozkan, Y. (2018). Effect of polymer type on characteristics of buccal tablets using factorial design. Saudi Pharmaceutical Journal, 26(1), 53-63. [CrossRef]
  • 20. Dalvi, S.V., Dave, R.N. (2009). Controlling particle size of a poorly water-soluble drug using ultrasound and stabilizers in antisolvent precipitation. Industrial & Engineering Chemistry Research, 48(16), 7581-7593. [CrossRef]
  • 21. Wang, Y., Zheng, Y., Zhang, L., Wang, Q., Zhang, D. (2013). Stability of nanosuspensions in drug delivery. Journal of Controlled Release, 172(3), 1126-1141. [CrossRef]
  • 22. Hao, J., Gao, Y., Zhao, J., Zhang, J., Li, Q., Zhao, Z., Liu, J. (2015). Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design. AAPS PharmSciTech, 16(1), 118-128. [CrossRef]
  • 23. Maaz, A., Abdelwahed, W., Tekko, I., Trefi, S. (2015). Influence of nanoprecipitation method parameters on nanoparticles loaded with gatifloxacin for ocular drug delivery. International Journal of Academic Research, (1), 1-12.

İNDOMETAZİN İÇEREN NANOSÜSPANSİYONLARIN GELİŞTİRİLMESİ VE FAKTÖRİYEL TASARIM YAKLAŞIMI KULLANILARAK OPTİMİZASYONU

Yıl 2023, Cilt: 47 Sayı: 2, 324 - 335, 20.05.2023

Gizem Rüya Topal Cansel Köse Özkan Yalçın Özkan

https://doi.org/10.33483/jfpau.1194470

Öz

Amaç: Bu çalışmada biyofarmasötik sınıflandırma sistemine göre (BCS) 2. sınıfta bulunan indometazinin nanosüspansiyon formülasyonlarının hazırlanması ve kritik formülasyon ve işlem basamaklarının belirlenmesi amaçlanmıştır. Formülasyonların hazırlanması sırasında 34 faktöriyel tasarım uygulanmış ve partikül büyüklüğü ve dağılımı incelenmiştir.
Gereç ve Yöntem: Çalışmada, nanosüspansiyonlar solvan/antisolvan yöntemi kullanılarak hazırlanmıştır. En iyi formülasyonu elde edebilmek adına Design Expert programı ile 34 faktöriyel tasarım uygulanmıştır. PVA konsantrasyonu, PVA molekül ağırlığı, solvan/antisolvan oranı ve etanol/PEG 300 oranı formülasyon parametresi olarak kullanılmıştır ve bu parametrelerin değişikliğinin partikül büyüklüğü ve dağılımı üzerine olan etkisi incelenmiştir.
Sonuç ve Tartışma: Nanosüspansiyonlar solvan/antisolvan yöntemi ile başarılı bir şekilde hazırlanmıştır. Nanosüspansiyonların partikül boyutu ve polidispersite indeksinin hem molekül ağırlığından hem de antisolvan fazdaki PVA yüzdesinden etkilendiği bulunmuştur (p ˂ 0.05). %0.2 PVA; PVA için 3000 molekül ağırlığı ve 3:50 çözücü-antisolvan oranı, nanosüspansiyon formülasyonları için optimal parametreler olarak bulunmuştur. Optimum formülasyonun partikül boyutu 301.5 ± 31.1 nm ve polidispersite indeksi 0.159 ± 0.035 olarak tespit edilmiştir.

Anahtar Kelimeler

Faktöriyel dizayn solvent/antisolvent metot İndometazin Nanosüspansiyon

Kaynakça

  • 1. Ahmadi Tehrani, A., Omranpoor, M.M., Vatanara, A., Seyedabadi, M., Ramezani, V. (2019). Formation of nanosuspensions in bottom-up approach: theories and optimization. DARU Journal of Pharmaceutical Sciences, 27(1), 451-473. [CrossRef]
  • 2. Ghosh, I., Schenck, D., Bose, S., Liu, F., Motto, M. (2013). Identification of critical process parameters and its interplay with nanosuspension formulation prepared by top down media milling technology-a QbD perspective. Pharmaceutical Development & Technology, 18(3), 719-729. [CrossRef]
  • 3. Ghosh, I., Schenck, D., Bose, S., Ruegger, C. (2012). Optimization of formulation and process parameters for the production of nanosuspension by wet media milling technique: effect of Vitamin E TPGS and nanocrystal particle size on oral absorption. European Journal of Pharmaceutical Sciences, 47(4), 718-728. [CrossRef]
  • 4. Patravale, V.B., Date, A.A., Kulkarni, R.M. (2004). Nanosuspensions: A promising drug delivery strategy. Journal of Pharmacy and Pharmacology, 56(7), 827-840. [CrossRef]
  • 5. Verma, S., Lan, Y., Gokhale, R., Burgess, D.J. (2009). Quality by design approach to understand the process of nanosuspension preparation. International Journal of Pharmaceutics, 377(1-2), 185-198. [CrossRef]
  • 6. Patel, V.R., Agrawal, Y.K. (2011). Nanosuspension: An approach to enhance solubility of drugs. Journal of Advanced Pharmaceutical Technology & Research, 2(2), 81-87. [CrossRef]
  • 7. Mahesh, K.V., Singh, S.C., Gulati, M. (2014). A comparative study of top-down and bottom-up approaches for the preparation of nanosuspensions of glipizide. Powder Technology, 256, 436-449. [CrossRef]
  • 8. Esim, O., Bakirhan, N.K., Yildirim, N., Sarper, M., Savaser, A., Ozkan, S.A., Ozkan, Y. (2020). Development, optimization and in vitro evaluation of oxaliplatin loaded nanoparticles in non-small cell lung cancer. DARU Journal of Pharmaceutical Sciences, 28(2), 673-684. [CrossRef]
  • 9. Gajera, B.Y., Shah, D.A., Dave, R.H. (2019). Development of an amorphous nanosuspension by sonoprecipitation-formulation and process optimization using design of experiment methodology. International Journal of Pharmaceutics, 559, 348-359. [CrossRef]
  • 10. 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), 213-220. [CrossRef]
  • 11. Shariare, M.H., Sharmin, S., Jahan, I., Reza, H.M., Mohsin, K. (2018). The impact of process parameters on carrier free paracetamol nanosuspension prepared using different stabilizers by antisolvent precipitation method. Journal of Drug Delivery Science and Technology, 43,122-1228. [CrossRef]
  • 12. Shariare, M.H., Altamimi, M.A., Marzan, A.L., Tabassum, R., Jahan, B., Reza, H.M., Rahman, M., Ahsan, G.U., Kazi, M. (2019). In vitro dissolution and bioavailability study of furosemide nanosuspension prepared using design of experiment (DoE). Saudi Pharmaceutical Journal, 27(1), 96-105. [CrossRef]
  • 13. Mishra, B., Sahoo, J., Dixit, P.K. (2016). Enhanced bioavailability of cinnarizine nanosuspensions by particle size engineering: Optimization and physicochemical investigations. Materials Science and Engineering: C, 63, 62-69. [CrossRef]
  • 14. Karakucuk, A., Celebi, N. (2020). Investigation of formulation and process parameters of wet media milling to develop etodolac nanosuspensions. Pharmaceutical Research, 37(6), 111. [CrossRef]
  • 15. Bolton, S., Bor, S. (2003). Pharmaceutical Statistics: Practical and Clinical Applications, Revised and Expanded, CRC Press.
  • 16. Anwer, M.K., Al-Mansoor, M.A., Jamil, S., Al-Shdefat, R., Ansari, M.N., Shakeel, F. (2016). Development and evaluation of PLGA polymer based nanoparticles of quercetin. International Journal of Biological Macromolecules, 92, 213-219. [CrossRef]
  • 17. Patil, A.S., Hegde, R., Gadad, A.P., Dandagi, P.M., Masareddy, R., Bolmal, U. (2021). Exploring the solvent-anti-solvent method of nanosuspension for enhanced oral bioavailability of lovastatin. Turkish Journal of Pharmaceutical Sciences, 18(5), 541-549. [CrossRef]
  • 18. Kuk, D.H., Ha, E.S., Ha, D.H., Sim, W.Y., Lee, S.K., Jeong, J.S., Kim, J.S., Baek, I.H., Park, H., Choi, D.H., Yoo, J.W., Jeong, S.H., Hwang, S.J., Kim, M.S. (2019). Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach. Pharmaceutics, 11(12), 688. [CrossRef]
  • 19. Esim, O., Savaser, A., Ozkan, C.K., Bayrak, Z., Tas, C., Ozkan, Y. (2018). Effect of polymer type on characteristics of buccal tablets using factorial design. Saudi Pharmaceutical Journal, 26(1), 53-63. [CrossRef]
  • 20. Dalvi, S.V., Dave, R.N. (2009). Controlling particle size of a poorly water-soluble drug using ultrasound and stabilizers in antisolvent precipitation. Industrial & Engineering Chemistry Research, 48(16), 7581-7593. [CrossRef]
  • 21. Wang, Y., Zheng, Y., Zhang, L., Wang, Q., Zhang, D. (2013). Stability of nanosuspensions in drug delivery. Journal of Controlled Release, 172(3), 1126-1141. [CrossRef]
  • 22. Hao, J., Gao, Y., Zhao, J., Zhang, J., Li, Q., Zhao, Z., Liu, J. (2015). Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design. AAPS PharmSciTech, 16(1), 118-128. [CrossRef]
  • 23. Maaz, A., Abdelwahed, W., Tekko, I., Trefi, S. (2015). Influence of nanoprecipitation method parameters on nanoparticles loaded with gatifloxacin for ocular drug delivery. International Journal of Academic Research, (1), 1-12.
Toplam 23 adet kaynakça vardır.

Ayrıntılar

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

Gizem Rüya Topal 0000-0002-7715-6383

Cansel Köse Özkan 0000-0002-4340-7279

Yalçın Özkan 0000-0001-5163-6867

Erken Görünüm Tarihi 17 Mayıs 2023
Yayımlanma Tarihi 20 Mayıs 2023
Gönderilme Tarihi 15 Kasım 2022
Kabul Tarihi 7 Ocak 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 47 Sayı: 2

Kaynak Göster

APA Topal, G. R., Köse Özkan, C., & Özkan, Y. (2023). DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES. Journal of Faculty of Pharmacy of Ankara University, 47(2), 324-335. https://doi.org/10.33483/jfpau.1194470
AMA Topal GR, Köse Özkan C, Özkan Y. DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES. Ankara Ecz. Fak. Derg. Mayıs 2023;47(2):324-335. doi:10.33483/jfpau.1194470
Chicago Topal, Gizem Rüya, Cansel Köse Özkan, ve Yalçın Özkan. “DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES”. Journal of Faculty of Pharmacy of Ankara University 47, sy. 2 (Mayıs 2023): 324-35. https://doi.org/10.33483/jfpau.1194470.
EndNote Topal GR, Köse Özkan C, Özkan Y (01 Mayıs 2023) DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES. Journal of Faculty of Pharmacy of Ankara University 47 2 324–335.
IEEE G. R. Topal, C. Köse Özkan, ve Y. Özkan, “DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES”, Ankara Ecz. Fak. Derg., c. 47, sy. 2, ss. 324–335, 2023, doi: 10.33483/jfpau.1194470.
ISNAD Topal, Gizem Rüya vd. “DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES”. Journal of Faculty of Pharmacy of Ankara University 47/2 (Mayıs 2023), 324-335. https://doi.org/10.33483/jfpau.1194470.
JAMA Topal GR, Köse Özkan C, Özkan Y. DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES. Ankara Ecz. Fak. Derg. 2023;47:324–335.
MLA Topal, Gizem Rüya vd. “DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES”. Journal of Faculty of Pharmacy of Ankara University, c. 47, sy. 2, 2023, ss. 324-35, doi:10.33483/jfpau.1194470.
Vancouver Topal GR, Köse Özkan C, Özkan Y. DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES. Ankara Ecz. Fak. Derg. 2023;47(2):324-35.
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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.