DEVELOPMENT AND OPTIMIZATION OF INDOMETHACIN NANOSUSPENSIONS USING DESIGN OF EXPERIMENT APPROACHES

Year 2023, Volume: 47 Issue: 2, 324 - 335, 20.05.2023

Gizem Rüya Topal , Cansel Köse Özkan , Yalçın Özkan

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

Abstract

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.

Keywords

Factorial design, Solvent/antisolvent method, Indomethacin, Nanosuspension

İNDOMETAZİN İÇEREN NANOSÜSPANSİYONLARIN GELİŞTİRİLMESİ VE FAKTÖRİYEL TASARIM YAKLAŞIMI KULLANILARAK OPTİMİZASYONU

Abstract

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.

Keywords

Faktöriyel dizayn, solvent/antisolvent metot, İndometazin, Nanosüspansiyon

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