Original Article

Development of Oral Tablet Formulation Containing Erlotinib: Randomly Methylated-β-cyclodextrin Inclusion Complex Using Direct Compression Method

10.4274/tjps.galenos.2021.95680

  • Nazlı Erdoğar

Received Date: 06.11.2020 Accepted Date: 15.02.2021 Turk J Pharm Sci 0;0(0):0-0 [e-Pub]

INTRODUCTION:

Erlotinib (ERL) is an tyrosine kinase inhibitor that has been used for metastatic non-small cell lung cancer (NSCLC). However, low aqueous solubility limits absorption and oral bioavailability hence complexation is applied to overcome these drawbacks. The aim of this study was to design and characterize oral tablet formulation containing ERL: randomly methylated-ß-cyclodextrin cyclodextrin (RAMEB CD) inclusion complex in order to enhance solubility and oral bioavailability for ERL.

METHODS:

An inclusion complex was prepared with RAMEB CD using co-lyophilization technique. Physicochemical studies was performed by X-ray diffractometry (XRD) and Fourier-transform infrared spectroscopy (FT-IR). 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. Also, flow properties of powder were determined.

RESULTS:

The characterization studies suggested that stable complexes between ERL and RAMEB were obtained with co-lyophilization method. Accordingly, tablet formulation using inclusion complex of ERL and RAMEB CD with drug dose equivalent to 25 mg was 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; Hausner ratio (HR): 1.05 ± 0.02; compressibility index: 14.27±1.55). Moisture content (%) was found as 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. Friability value was 0.27%. In uniformity of weight test, the average weight was 404.57 ± 1.6 mg, with less than 5% deviation for randomly selected 20 tablets. The disintegration time was found to be less than 15 min. Dissolution study showed that solubility of erlotinib was importantly increased by complexation with randomly methylated-ß-cyclodextrin. 99% drug was released from tablet formulation at 60 min.

DISCUSSION AND CONCLUSION:

These results concluded that a new tablet formulation of ERL: RAMEB CD inclusion complex could be an alternative approach for achieving better dissolution and oral bioavailability in NSCLC treatment.

Keywords: erlotinib, inclusion complex, direct compression, dissolution