Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method
Yıl: 2021 Cilt: 18 Sayı: 5 Sayfa Aralığı: 72 - 78 Metin Dili: İngilizce DOI: 10.4274/tjps.galenos.2021.95680 İndeks Tarihi: 19-01-2022
Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method
Öz: Objectives: Erlotinib (ERL) is a tyrosine kinase inhibitor that has been used in the treatment of metastatic non-small cell lung cancer (NSCLC). However, its low aqueous solubility limits its absorption and oral bioavailability. To overcome these pharmacokinetic drawbacks, complexation of ERL can be applied. The aim of this study was to develop and characterize an oral tablet formulation containing ERL: Randomly methylated-βcyclodextrin (RAMEB-CD) inclusion complex to enhance solubility and oral bioavailability of ERL. Materials and Methods: An inclusion complex was prepared with RAMEB-CD using co-lyophilization technique. Structural characterization was performed using X-ray diffractometry and fourier-transform infrared spectroscopy. Tablet formulation of ERL: RAMEB-CD inclusion complex were prepared using direct compression technique. Tablet characteristics like hardness, diameter, thickness, friability, weight variability, disintegration and dissolution were evaluated. Flow properties of the powder were also determined. Results: Characterization studies suggested that stable complexes between ERL and RAMEB-CD were obtained with co-lyophilization method. Tablet formulation using inclusion complex of ERL and RAMEB-CD with drug dose equivalent to 25 mg was successfully prepared using direct compression technique. Physical properties of the powder mixture were studied - angle of repose (°): 34.27±1.78; flow time: 2.2±0.4; HR: 1.05±0.02; compressibility index: 14.27±1.55. Moisture content (%) was found to be 0.27±0.05. The thickness, diameter and hardness values were 3.92±0.05 mm, 11.3±0.06 mm and 81.38±2.27 N, respectively. In uniformity of weight test, the average weight was 404.57±1.6mg, with less than 5% deviation in 20 randomly selected tablets. Friability value was 0.27% and the disintegration time was found to be less than 15 min. Importantly, dissolution study showed that solubility of ERL was increased by complexation with RAMEB-CD. After 60 minutes, 99% of drug was released from the tablet formulation. Conclusion: These results demonstrate that a new tablet formulation of ERL: RAMEB-CD inclusion complex could be an alternative approach to achieve increased dissolution and oral bioavailability of ERL for NSCLC treatment.
Anahtar Kelime: Doğrudan Basım Yöntemi Kullanılarak Randomize Metillenmişβ-siklodekstrin İnklüzyon Kompleksi İçeren Erlotinib Oral Tablet Formülasyonu Geliştirilmesi
Öz: Amaç: Erlotinib (ERL) metastatik küçük hücreli akciğer kanserinde (NSCLC) kullanılan tirozin kinaz inhibitörüdür. Bununla birlikte, düşük suda çözünürlüğü absorpsiyonunu ve oral biyoyararlanımını sınırlamaktadır. Bu sakıncaların üstesinden gelmek için kompleksleşme yöntemi kullanılmaktadır. Çalışmanın amacı ERL’nin çözünürlüğünü ve oral biyoyararlanımını artırmak için ERL: Randomize metillenmiş β-siklodekstrin (RAMEB-CD) inklüzyon kompleksi içeren oral tablet formülasyonu geliştirilmesi ve bu formülasyonun karakterize edilmesidir. Gereç ve Yöntemler: RAMEB-CD siklodekstrin içeren inklüzyon kompleksi ko-liyofilizasyon yöntemi ile hazırlanmıştır. X-ray difraktometresi ve fourier-transform infrared spektroskopisi kullanılarak fizikokimyasal karakterizasyon yapılmıştır. Direkt basım yöntemi ile ERL: RAMEB CD siklodekstrin inklüzyon kompleksi içeren tablet formülasyonu hazırlanmıştır. Sertlik, çap, kalınlık, kırılganlık, ağırlık değişkenliği, dağılma ve dissolüsyon gibi tablet özellikleri belirlenmiştir. Tozun akış özellikleri de tayin edilmiştir. Bulgular: Karakterizasyon çalışmaları ko-liyofilizasyon tekniği ile ERL ve RAMEB-CD arasında stabil kompleks elde edildiğini göstermiştir. Buna göre, direkt basım yöntemi ile 25 mg ilaç dozuna eşdeğer olacak şekilde ERL ve RAMEB-CD inklüzyon kompleksi kullanılarak tablet formülasyonu hazırlanmıştır. Toz karışımının fiziksel özellikleri belirlenmiştir yığın açısı (°): 34,27±1,78; akış süresi: 2,2±0,4; Hausner oranı: 1,05±0,02; basılabilirlik indeksi: 14,27±1,55). Nem içeriği %0,27±0,05 bulunmuştur. Kalınlık, çap ve sertlik değerleri sırasıyla 3,92±0,05 mm, 11,3±0,06 mm ve 81,38±2,27 N olarak bulunmuştur. Ağırlık sapması testinde; ortalama tablet ağırlığı 404,57±1,6mg olup rastgele seçilen 20 tablet için sapma %5’ten küçüktür. Kırılganlık değeri %0,27’dir. Dağılma zamanı 15 dakikadan az bulunmuştur. Dissolüsyon çalışması RAMEB-CD ile kompleksleşme ile ERL’nin suda çözünürlüğünün önemli ölçüde arttığını göstermiştir. Altmış dakika sonunda ilacın %99’u salınmıştır. Sonuç: Elde edilen veriler ile ERL: RAMEB-CD inklüzyon kompleksi içeren yeni tablet formülasyonunun daha iyi çözünme ve oral biyoyararlanım elde etmek için NSCLC tedavisinde alternatif bir yaklaşım olabileceği sonucuna varılmıştır.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | ERDOĞAR N (2021). Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. , 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| Chicago | ERDOĞAR NAZLI Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. (2021): 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| MLA | ERDOĞAR NAZLI Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. , 2021, ss.72 - 78. 10.4274/tjps.galenos.2021.95680 |
| AMA | ERDOĞAR N Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. . 2021; 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| Vancouver | ERDOĞAR N Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. . 2021; 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| IEEE | ERDOĞAR N "Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method." , ss.72 - 78, 2021. 10.4274/tjps.galenos.2021.95680 |
| ISNAD | ERDOĞAR, NAZLI. "Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method". (2021), 72-78. https://doi.org/10.4274/tjps.galenos.2021.95680 |
| APA | ERDOĞAR N (2021). Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. Turkish Journal of Pharmaceutical Sciences, 18(5), 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| Chicago | ERDOĞAR NAZLI Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. Turkish Journal of Pharmaceutical Sciences 18, no.5 (2021): 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| MLA | ERDOĞAR NAZLI Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. Turkish Journal of Pharmaceutical Sciences, vol.18, no.5, 2021, ss.72 - 78. 10.4274/tjps.galenos.2021.95680 |
| AMA | ERDOĞAR N Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. Turkish Journal of Pharmaceutical Sciences. 2021; 18(5): 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| Vancouver | ERDOĞAR N Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method. Turkish Journal of Pharmaceutical Sciences. 2021; 18(5): 72 - 78. 10.4274/tjps.galenos.2021.95680 |
| IEEE | ERDOĞAR N "Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method." Turkish Journal of Pharmaceutical Sciences, 18, ss.72 - 78, 2021. 10.4274/tjps.galenos.2021.95680 |
| ISNAD | ERDOĞAR, NAZLI. "Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method". Turkish Journal of Pharmaceutical Sciences 18/5 (2021), 72-78. https://doi.org/10.4274/tjps.galenos.2021.95680 |
