Oral Formulation of Anticancer Agents for Colon Cancer

Aims/Objective: To develop and estimate enteric-coated capsules containing mucoadhesive Microspheres of Capecitabine and Oxaliplatin to treat Colon cancer.

Study Design: Box Behnken.

Place and Duration of Study: Department of Pharmaceutics, Parul Institute of Pharmacy and Research, Parul University, Vadodara, between 2017 to 2021.

Methodology: Capecitabine and Oxaliplatin are used as antineoplastic agents and can be delivered via the oral route of administration. For the estimation of drugs Analytical method has been developed by HPLC. Box Behnken design has been used to optimize Drug: polymer ratio (1:2), Inlet temperature 170ºC, and crosslinking agent with a 0.5 ml 1% Gluteraldehyde solution.

The microspheres were successfully prepared by using the spray drying technique and evaluated.

Results: The results of optimized Capecitabine microspheres were obtained as Particle size 87.91 µm ± 0.274,% yield 57.21± 1.5,% Mucoadhesion 57.21± 1.5,% entrapment efficiency 82.16± 0.725. The results of optimized Oxaliplatin microspheres were obtained as Particle size 99.88µm±0.034,% yield 56.0± 0.088,% Mucoadhesion 87.0± 0.80,% entrapment efficiency 82.61±0.085. The drug content of Capecitabine and Oxaliplatin in the filled capsule was 94.67% ±0.32 and 93.45%±0.712, respectively. % Drug release of Capecitabine and Oxaliplatin in Phosphate buffer pH 7.4 was found to be 94.83±0.22 and 96.94±0.11 respectively after 8 hrs. Stability study at 400C±20C / 75 ± 5 % RH revealed that there was no significant change in disintegration time, drug content and % CDR during 6 months. So, prepared formulation was stable during stability study. MTT assay has been performed on the formulation of Capecitabine and Oxaliplatin microspheres for assessing the % viability of both the drugs on the Caco-2 cell line.

Conclusion: The present study confirmed that prepared mucoadhesive microspheres filled with enteric-coated capsules have an antitumor effect on colon cancer cells. The formulation induced high cell death within 48 hours, and less cell viability was obtained compared to API. Six months accelerated Stability study indicates that formulation is fairly stable at storage conditions.