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

Turk J Pharm Sci. 2021 Oct 28;18(5):589-596. doi: 10.4274/tjps.galenos.2021.95680.


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-β-cyclodextrin (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±1.6 mg, 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.

Keywords: Erlotinib; direct compression; dissolution; inclusion complex.