Exploring the Solvent-Anti-solvent Method of Nanosuspension for Enhanced Oral Bioavailability of Lovastatin

Objectives: Lovastatin is an antilipidemic drug that belongs to the class of statins that has poor oral bioavailability due to its low solubility and variable dissolution rate. The main aim of this study was to enhance the solubility and dissolution rate of the drug and understand its oral bioavailability. Materials and Methods: Lovastatin nanosuspension was formulated using a solventanti-solvent method using a probe sonication technique. A nanosuspension was prepared, using hydroxypropyl methylcellulose (HPMC) K15M and pluronic F68 as stabilizers. The formulated nanosuspensions were characterized for particle size, polydispersity index (PDI) zeta potential, surface morphology, and in vitro release rate. Further, an in vivo bioavailability study and stability studies were also performed. Results: Optimized formulation showed a particle size of 127±0.01 nm, a PDI of 0.492±0.001, and a zeta potential of -37.9 mV, which indicates good stability. Morphological study showed that the particles were in the nano range. The drug content was found to be in the range of 73-87%. In vitro release revealed much faster release of the drug in one hour compared to the pure drug and its marketed formulation. In vivo bioavailability study was carried out in Wistar rats, which showed improvement in bioavailability by approximately 2.5 folds compared with the marketed formulation. Stability studies indicated that the optimized formulation F2 was more stable at 4°C±2°C. Conclusion: The prepared lovastatin nanosuspension showed improvement in solubility, dissolution rate, and oral bioavailability compared to the pure drug and its marketed formulation. Hence, lovastatin nanosuspension may be a potentially valuable tool for improving the oral bioavailability of lovastatin.

Lovastatinin Gelişmiş Oral Biyoyararlanımı İçin Solvent-Anti-solvent Yöntemi ile Hazırlanan Nanosüspansiyon Formülasyonunun Araştırılması

Amaç: Lovastatin, düşük çözünürlüğü ve değişken çözünme hızı nedeniyle oral biyoyararlanımı zayıf olan statinler sınıfına ait antilipidemik bir ilaçtır. Bu çalışmanın temel amacı, ilacın çözünürlüğünü ve çözünme hızını artırmak ve oral biyoyararlanımını belirlemektir. Gereçler ve Yöntemler: Lovastatin içeren nanosüspansiyon, bir prob sonikasyon tekniği kullanılarak solvent-anti-solvent yöntemi kullanılarak formüle edildi. Stabilizatör olarak hidroksipropil metilselüloz (HPMC) K15M ve pluronic F68 kullanılarak bir nanosüspansiyon hazırlandı. Formüle edilen nanosüspansiyonlar, partikül boyutu, polidispersite indeksi (PDI), zeta potansiyeli, yüzey morfolojisi ve in vitro salım profilleri belirlenerek karakterize edildi. Ayrıca, in vivo biyoyararlanım çalışması ve stabilite çalışmaları da gerçekleştirilmiştir. Bulgular: Optimize edilmiş formülasyonun, partikül boyutu 127±0,01 nm, PDI değeri 0,492±0,001 ve zeta potansiyeli -37,9 mV olarak belirlendi, bu da formülasyonun iyi bir stabiliteye sahip olduğunu gösterdi. Morfolojik çalışma, partiküllerin nano aralıkta olduğunu gösterdi. İlaç içeriği %73- 87 aralığında bulundu. İn vitro salım, saf ilaca ve ticari formülasyona kıyasla ilacın bir saat içinde çok daha hızlı salım profili gösterdiğini ortaya çıkardı. İn vivo biyoyararlanım çalışması Wistar sıçanlarında gerçekleştirildi ve nanosüspansiyon formülasyonunda ticari formülasyona kıyasla biyoyararlanımda yaklaşık 2,5 kat iyileşme olduğunu gösterdi. Stabilite çalışmaları, optimize edilmiş F2 formülasyonunun 4°C±2°C’de daha stabil olduğunu gösterdi. Sonuç: Hazırlanan lovastatin nanosüspansiyonu, saf ilaca ve ticari formülasyonuna kıyasla çözünürlük, çözünme hızı ve oral biyoyararlanım açısından gelişme göstermiştir. Bu nedenle, lovastatin nanosüspansiyonunun, lovastatinin oral biyoyararlanımını geliştirmek için potansiyele sahip olduğu sonucuna ulaşıldı.

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Turkish Journal of Pharmaceutical Sciences
  • ISSN: 1304-530X
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 2000

6.2b279

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